REINFORCED HYDROGELS FOR SCAR REMEDIATION · 2011-03-28 · Polymer Nanostructured-materials, RMIT , Melbourne, June 2009. B. Radi, M. Wellard and G. George, “Sol-gel Reactions

REINFORCED HYDROGELS FOR

SILICONE COPOLYMER DELIVERY

FOR SCAR REMEDIATION

A thesis presented to

THE QUEENSLAND UNIVERSITY OF TECHNOLOGY

In fulfilment of the requirements for the degree of

Doctor of Philosophy

Submitted by

Babak Radi

Under the supervision of

Professor Graeme George

Faculty of Science and Technology

Institute of Health and Biomedical Innovation

October, 2010

i

Statement of Original Authorship

The work contained in this thesis has not been previously submitted to meet

requirements for an award at this or any other higher education institution. To the best of

my knowledge and belief, the thesis contains no material previously published or written

by another person except where due reference is made.

Signature

Date

ii

Abstract

Hypertrophic scars are formed by collagen overproduction in wounded areas and

often occur in victims of severe burns. There are several methods for hypertrophic scar

remediation and silicone gel therapy is one of the more successful methods. Research by

others has shown that the activity of these gels may be due to migration of amphiphilic

silicone oligomers from the gel and into the dermis, down-regulating production of

collagen by fibroblasts. Normal silicone oil (PDMS) does not produce the same effect

on fibroblasts. The main purpose of this project is the introduction of a particular

amphiphilic silicone rake copolymer into an appropriate network which can absorb and

release the silicone copolymer on the scarred area. Hydrogels are polymeric crosslinked

networks which can swell in water or a drug solution, and gradually release the drug

when applied to the skin. The application of gel enhances the effectiveness of the

therapy, reduces the period of treatment and can be comfortable for patients to use.

Polyethylene glycol (PEG) based networks have been applied in this research,

because the amphiphilic silicone rake copolymer to be used as a therapy has

polyethylene oxide (PEO) as a side chain. These PEO side chains have very similar

chemical structure to a PEG gel chain so enhancing both the compatibility and the

diffusion of the amphiphilic silicone rake copolymer into and out of the gel.

Synthesis of PEG-based networks has been performed by two methods: in situ

silsesquioxane formation as crosslink with a sol-gel reaction under different conditions

and UV curing. PEG networks have low mechanical properties which is a fundamental

limitation of the polymer backbone. For mechanical properties enhancement, composite

networks were synthesized using nano-silica with different surface modification. The

chemical structure of in situ silsesquioxane in the dry network has been examined by

Solid State NMR, Differential Scanning Calorimetry (DSC) and swelling measurements

in water. Mechanical properties of dry networks were tested by Dynamic Mechanical

Thermal Analysis (DMTA) to determine modulus and interfacial interaction between

silica and the network. In this way a family of self-reinforced networks has been

iii

produced that have been shown to absorb and deliver the active amphiphilic silicone-

PEO rake copolymer.

iv

List of Presentations and Publication Oral presentation

B. Radi and G. George, “Hydrogels for Silicone Delivery in Burns Scar Remediation”

30th Australasian Polymer Symposium, Melbourne, December, 2008.

Poster Presentation

B. Radi and G. George, “Nanosilica Reinforced Hydrogels for Delivery of Silicone

Therapies” in International Symposium on Recent Developments and Applications in

Polymer Nanostructured-materials, RMIT , Melbourne, June 2009.

B. Radi, M. Wellard and G. George, “Sol-gel Reactions as a Novel Method of Synthesis

of Hydrogels to Release Silicone for Scar Remediation” in 8th International IUPAC

Conference on Polymer-Solvent Complexes and Intercalates, POLYSOLVAT-8, in

Institut Charles Sadron, Strasbourg, France, July 2010.

B. Radi, M. Wellard and G. George, “Sol-gel Reactions as a Novel Method of Synthesis

of Hydrogels for Silicone Scar Remediation Therapy” in 43rd IUPAC World Polymer

Congress, MACRO2010, in the Scottish Exhibition and Conference Centre (SECC),

Glasgow, Scotland, July 2010.

Publication

Radi B., Wellard M. and George G., Controlled Poly (ethylene glycol) Network

Structures Through Silsesquioxane Crosslinks Formed by Sol-gel Reactions.

Macromolecules, Accepted, October 2010.

v

List of Abbreviations APTES (3-Aminopropyl) triethoxysilane

CMC critical micellization concentration

DCM dichloromethane

DMAP 4-dimethylaminopyridine

DMTA Dynamic Mechanical Thermal Analysis

DSC Differential Scanning Calorimetry

EDC 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride

Et3N triethylamine

FDA U.S. Food and Drug Administration

FTIR-ATR Fourier Transform Infra Red Attenuated Total Reflectance

FT-Raman Fourier Transform Raman

GPS (3-Glycidyloxypropyl)trimethoxysilane

HCl hydrochloric acid

1H NMR proton nuclear magnetic resonance

HPLC high performance liquid chromatography

LCST lower critical solution temperature

MALDI-MS Matrix Assisted Laser Desorption Ionization Mass Spectrometry

NaH sodium hydride

PDI poly dispersity index

PDMS polydimethylsiloxane

PEG poly (ethylene glycol)

PEO poly (ethylene oxide) (poly (ethylene glycol) monomethyl ether)

vi

PPG poly (propylene glycol)

PTSA p-toluenesulfonic acid

Rg Radius of gyration

SC step crystallization from the melt

29Si NMR silicon nuclear magnetic resonance

SSA self-nucleation and annealing

Tg glass transition temperature

TEOS Tetraethyl orthosilicate

TGA thermogravimetric analysis

THF tetrahydrofuran

UCST upper critical solution temperature

XRD X-ray Diffraction

vii

Acknowledgements I would like to acknowledge and sincerely thank all of the people who have

helped me in this project, particularly:

My principal supervisor, Professor Graeme George for the very valuable

guidance and support he has given me through this project and thesis. I have learnt in-

depth knowledge of polymer science and chemistry from him.

My associate supervisor, Professor Peter Fredricks who has taught me

fundamentals of vibrational spectroscopy.

Professor Andrew Whittaker (University of Queensland) and Doctor Wael Gafor

who helped me to use all instruments in the thermal analysis laboratory at University of

Queensland.

Doctor Mark Wellard and Doctor John Bartley (Queensland University of

Technology) for their help and training me to operate Nuclear Magnetic Resonance

(NMR) and the many discussions we have had for analysis of results.

I would like to acknowledge the financial support of ARC for my final year

scholarship and Queensland University of Technology and Science Faculty for

providing me a fee waiver scholarship.

I would like to thank the past and present members of QUT chemistry

postgraduate students and staff, particularly the QUT polymer group.

Finally, I would also like to thank my mother, sister and brother for all kinds of

encouraging support which I have received through my study.

viii

PREFACE This preface gives the outline for the thesis and indicates the novel aspects of this

study. This thesis has a target of producing tailored crosslinked networks through sol-gel

reactions of silica precursors which form in situ crosslinking and reinforcing sites. These

are designed as delivery vehicles for amphiphilic oligomeric siloxane copolymers which

have the potential for scar remediation. Since this is a rake copolymer with

poly(ethylene oxide), gels based on poly(ethylene glycol) have been researched as

chemically compatible carriers.

In this thesis the systems studied are formally gels not hydrogels, particularly

when they are characterized in the absence of water. Swollen crosslinked polymeric

networks, depending on their application and environment, can be divided in two sub-

groups: hydrogel and gel. A gel swollen with water is conventionally termed a hydrogel

although in biomaterials this term is often applied to gels with greater than 95% water

content. In this study, when the network is dry or swollen in a non-aqueous liquid, it is

named a gel. The gel which is swollen in the amphiphilic oligomeric siloxane, and then

applied on the skin changes to a hydrogel due to water exchange. Consequently in this

thesis both terms are used.

In chapter one, after an introduction to the process of scar formation and

remediation, the theory of hydrogels, reinforced polymers, silica surface treatment and

methods for incorporating organic linker groups such as amide, urethane and epoxy ring

opening will be discussed. The principles of sol-gel chemistry are used to provide a

basis for the methodology developed in chapter two to produce the target materials. The

fundamentals of dynamic mechanical thermal analysis will be introduced as this is a

major characterization tool for the networks.

In chapter two, the methodology of experiments including synthetic strategies

and experimental conditions will be discussed. In particular the evolution of the methods

for synthesis of the materials in chapter three is given and the limitations to conventional

routes are discussed

ix

In chapter three, a novel method of gel synthesis will be described. In this

approach, PEG-based gels are formed through the sol-gel reaction (hydrolysis and

condensation) of organosilanes. In situ silsesquioxane units form the chemical junctions

in these hybrid organic-inorganic networks during sol-gel reactions. This novel method

is shown to enable the synthesis of hydrogels with different swelling properties by

changing the reaction conditions such as pH change and amount of added water. The

main advantage in this method is that the desired properties of the hydrogel can be

tailored and controlled by changes in reaction conditions.

In chapter four, it is shown that the mechanical properties of reinforced

hydrogels can be improved by adding nano-silica with different surface chemistry. The

interfacial properties between silica and polymer can be altered by applying different

surface treatments to silica that can control the interaction with the hydrogel polymer.

In chapter five, the swelling of the PEG-based gel by the silicone copolymer will

be studied. The effects of silicone copolymer molecular weight distribution on swelling

and silicone copolymer molecular weight distribution inside and outside of hydrogel at

equilibrium will be discussed. The uptake and release properties of the amphiphilic

oligomeric siloxane copolymer in the gel are assessed against the target of providing a

delivery vehicle for this potential scar-remediation therapy.

In chapter 6 further possible research in this field is discussed.

x

Table of Contents Chapter 1: Introduction ..................................................................................................1

1.1 Introduction......................................................................................................1 1.2 Different Methods of Hypertrophic Scar Treatment ...................................3

1.2.1 Silicone Therapy.......................................................................................3 1.2.3. Amphiphilic Silicone Rake Copolymer Therapy ..................................5 1.2.3. Delivery System for Amphiphilic Silicone Rake Copolymer ...............6

1.3 Networks as A Drug Delivery System ................................................................6 1.3.1 Structures of Networks............................................................................7

1.3.1.1 Nano-Structure of Crosslinked Networks .........................................7 1.3.2 Swelling and Release Mechanisms in Networks....................................9

1.3.2.1 Uptake and Release Based on Diffusion ..........................................10 1.3.3 Equilibrium Swelling Theories .............................................................12

1.4 Synthesis of Functionalized Poly (ethylene glycol) For Networks............13 1.4.1 Poly (ethylene glycol) (PEG) .................................................................13 1.4.2 Synthesis of Different Terminally Functionalized PEG .....................14

1.4.2.1 Synthesis of Bis (trialkoxy silyl propyl)-PEG ..................................14 1.4.2.1.1 Reaction of (3-Glycidyloxypropyl)trimethoxysilane (GPS) with PEG ……………………………………………………………………15 1.4.2.1.2 Reaction of 3-triethoxysilylpropylamine (APTES) with PEG .15 1.4.2.1.3 Reaction of 3-(triethoxysilyl)propyl isocyanate with PEG.......18

1.4.2.2 Synthesis of Bis acrylate PEG ...........................................................20 1.4.3 Synthesis of Networks from Functionalized PEG...............................21

1.4.3.1 Synthesis of Networks from Bis(trialkoxy propyl)-PEG (Sol-gel Reaction) .............................................................................................................21 1.4.3.2 Synthesis of Networks from Bis acrylate PEG ................................22

1.5 Mechanisms of Network formation in both Free Radical Polymerization and Sol-Gel Reactions ...........................................................................................................23

1.5.1 Free Radical Polymerization.................................................................23 1.5.2 Sol-gel Reaction in Organic-Inorganic Hybrid Polymer Formation in Crosslinked Network .............................................................................................26

1.5.2.1 Sol-Gel Reaction to Form in situ Silsesquioxane as Crosslinker with Bis(triethoxysilyl)-Polymer.......................................................................27

1.5.2.1.1 Sol-Gel Processing Reaction........................................................27 1.5.2.1.2 Mechanisms of Hydrolysis ..........................................................28 1.5.2.1.3 Acid-Catalyzed Hydrolysis Mechanism .....................................29 1.5.2.1.4 Base-Catalyzed Hydrolysis Mechanism .....................................31 1.5.2.1.5 Reaction Rates and Mechanism of Condensation.....................32 1.5.2.1.6 Steric and Inductive Effects in Condensation process..............32 1.5.2.1.7 Acid-Catalyzed Condensation.....................................................33 1.5.2.1.8 Base-Catalyzed Condensation.....................................................34

1.6 Reinforced Networks .....................................................................................35 1.6.1 Particulate Reinforced of low Modulus Materials ..............................35 1.6.2 Modification of the Surface of Silica ....................................................37

1.6.2.1 Silica structure ...................................................................................39

xi

1.6.2.2 Hybrid Silica Structure .................................................................... 40 1.7 Semicrystalline Polymer Properties and Structures in Networks ............ 41

1.7.1 Crystal and Amorphous Regions in Semicrystalline Polymers ........ 41 1.7.1.1 Amorphous Polymer ......................................................................... 42 1.7.1.2 Semicrystalline Polymer ................................................................... 42 1.7.1.3 Kinetics of Crystallization ................................................................ 43

1.7.2 Thermal Fractionation of Semi-crystalline Polymers........................ 43 1.8 Dynamic Mechanical Thermal Analysis (DMTA) ..................................... 44

1.8.1 Temperature Dependent Properties in Dynamic Mechanical Thermal Analysis .................................................................................................. 47

1.8.1.1 Glass Transition Temperature......................................................... 47 1.8.1.2 The α’-Transition in Semi-crystalline Polymers ............................ 49

1.9 Conclusion...................................................................................................... 51 Chapter 2: Experimental Methodology ...................................................................... 58

2.1 Functionalization of Silica Surface ............................................................. 58 2.1.1 Silica Surface Modification Procedure................................................ 58

2.2 Synthesis of Silane-Terminated Polyethylene glycol (PEG)...................... 59 2.2.1 Bis(trialkoxy silyl)-PEG Synthesis Procedure .................................... 59 2.2.2 Procedure for Synthesis of Polyethylene Oxide Silane with Different Organic Chain Length .......................................................................................... 61

2.3 Synthesis of Bis acrylate Polyethylene glycol (PEG) (Acrylate Diesters of PEG) ………………………………………………………………………………..62 2.4 Network Synthesis Procedure ...................................................................... 63

2.4.1 Reaction between Silica Surface and Chain End of PEG.................. 63 2.4.1.1 Attempted Synthesis of Networks by Direct Reaction between Silica and Bis(trialkoxy silyl propyl) PEG ...................................................... 63 2.4.1.2 Attempted Synthesis of Networks with Direct Reaction between Silane-modified Silica and PEG ....................................................................... 63 2.4.1.3 Attempted Synthesis of Networks by Direct Reaction between Amino-silane-modified Silica and Bis Epoxy-PEG ........................................ 64

2.4.2 Synthesis of Networks and Reinforced Networks with Hydrolysis and Condensation Reactions ....................................................................................... 65

2.4.2.1 Procedure for Synthesis of Networks with and without Silica in Solutions with Different pH ............................................................................. 65

2.4.3 Procedure of Synthesis of Networks from Bis acrylate PEG with and without Silica ......................................................................................................... 68

2.5 Sol Fraction Measurement ........................................................................... 70 2.6 Swelling Measurement.................................................................................. 70 2.7 Characterization Techniques and Instruments.......................................... 70

2.7.1 Differential Scanning Calorimetry (DSC) ......................................... 70 2.7.2 Fourier Transform Infrared (FT-IR).................................................. 71 2.7.3 FT-Raman Spectroscopy ...................................................................... 72 2.7.4 Gel Permeation Chromatography (GPC) ........................................... 72 2.7.4.1 Analytical GPC...................................................................................... 72 2.7.4.2 Preparative GPC ................................................................................... 72 2.7.5 Dynamic Mechanical Test (DMTA) .................................................... 72

xii

2.7.6 Nuclear Magnetic Resonance (NMR)...................................................73 2.7.7 Thermogravimetric Analysis (TGA) ....................................................73

Chapter 3: Synthesis of Novel poly (ethylene glycol) Based Networks with Formation of in Situ Silsesquioxane Crosslinkers.......................................................74

3.1 Introduction....................................................................................................74 3.2 Synthesis, Results and Discussion of Network formation ..........................75

3.2.1 Synthesis of Bis(trialkoxy silyl)-PEG Precursor .................................75 3.2.1.1 Reaction between 3-glycidoxypropyl trimethoxylsilane (GPS) and PEG ………………………………………………………………………..75 3.2.1.2 Reaction between 3-aminopropyltriethoxysilane (APTES) and PEG ………………………………………………………………………..77 3.2.1.3 Reaction between 3-(triethoxy silyl)propyl isocyanate and PEG ..79

3.2.2 Synthesis of Networks by Reaction between Hydrophilic Silica Surface and Bis(triethoxy silyl propyl urethane)-PEG in Dry Conditions (The First Possible Synthesis Strategy).........................................................................81

3.2.2.1 Reaction between Hybrid Silica and PEG with Epoxy End Groups ………………………………………………………………………..82 3.2.2.2 Model Reaction by Applying Organosilanes with Different Organic Groups..................................................................................................83

3.2.2.2.1 Characterization of Functionalized Silica with Different Silanes ……………………………………………………………………85

3.2.3 Synthesis of Network with Sol-gel Reactions (The Second Possible Synthesis Strategy).................................................................................................92

3.2.3.1 Synthesis of in Situ Silsesquioxane Structures as Crosslinker and Effects of Silsesquioxane Crosslinker Structures on Network Properties....92

3.2.3.1.1 Structure analysis by Differential Scanning Calorimetry (DSC) ……………………………………………………………………93 3.2.3.1.2 Effects of Amount of Acidic Water on the Sol-gel Reaction for Network Formation .....................................................................................100 3.2.3.1.3 Effects of Different Concentration of Hydrochloric Acid Solution on Sol-gel Reaction in the PEG 2000 Network...........................113 3.2.3.1.4 Effects of Different Concentration of Hydrochloric Acid Solution on Sol-gel Reaction in the PEG 400 Networks ...........................121 3.2.3.1.5 Effects of Amount of Acidic Water on the Sol-gel Reaction for PEG 400 Network Structures .....................................................................129 3.2.3.1.6 Effects of Different Concentration of Hydrochloric Acid Solution on Sol-gel Reaction in PEG 4600 Networks ...............................133 3.2.3.1.7 Synthesis of Networks Reinforced by Nano-Silica Using Sol-gel Reactions …………………………………………………………………..136

3.2.3.1.7.1 Synthesis of Reinforced Networks with Hydrophilic Silica Using a Sol-gel Reaction ..........................................................................137 3.2.3.1.7.2 Synthesis of Crosslinked PEG 400 Reinforced with Hydrophilic Silica Using a Sol-gel Reaction ..........................................143 3.2.3.1.7.3 Synthesis of Crosslinked PEG 400 Reinforced with Hydrophilic Silica in Sol-gel Reaction with Different Acid Concentration ...........................................................................................146

xiii

3.2.3.1.7.4 Network Formation with Base-catalyzed Hydrolysis and Condensation Reactions ......................................................................... 149 3.2.3.1.7.5 Network Formation with TEOS as Crosslinker.............. 153

3.3 Summary and Final Discussion ................................................................. 158 Chapter 4: Study of the Interface of Silica and Polymer in Nano-silica Reinforced Networks ...................................................................................................................... 163

4.1 Introduction ................................................................................................. 163 4.2 Reinforced Networks and Interfacial Properties ..................................... 164

4.2.1 Requirements for the Study of Interfacial Properties of Reinforced Networks .............................................................................................................. 164 4.2.2 Synthesis of Bis acrylate- PEG Precursor......................................... 164 4.2.3 Synthesis of Networks from Bis acrylate PEG ................................. 165 4.2.4 Results and Discussion of Properties of Reinforced Networks ....... 170

4.2.4.1 Effect of Silica Percentage on Dry Reinforced Networks............ 171 4.2.4.2 Effects of Hydrogen Bonding on tan δ .......................................... 172 4.2.4.3 Effects of Different Surface Chemistry of Silica on Reinforced PEG Networks ................................................................................................. 176 4.2.4.4 Effect of Different Length of Silica Surface Modifier on Reinforced PEG Networks ............................................................................. 184 4.2.4.5 Tensile Test on Reinforced Networks............................................ 192

4.3 Summary...................................................................................................... 195 Chapter 5: Sorption and Desorption of Silicone Fluids by PEG Gels.................... 199

5.1 Introduction ................................................................................................. 199 5.2 Swelling Study in PEG Based Networks ................................................... 200

5.2.1 Swelling Study in PEG Hydrogels with Water as Swelling Agent . 201 5.2.2 Swelling Study in PEG Networks with Amphiphilic Silicone Copolymer as Swelling agent ............................................................................ 202

5.2.2.1 Amphiphilic Silicone Copolymer ................................................... 202 5.2.2.2 Crosslinked PEG as Gels for Amphiphilic Rake Silicone Copolymer........................................................................................................ 206 5.2.2.3 Effect of Amphiphilic Silicone Rake Copolymer Size on Swelling Percentage and Profile in Gels ....................................................................... 218

5.3 Desorption of Amphiphilic Silicone Rake Copolymer from Swollen Gels ………………………………………………………………………………220 5.4 Summary...................................................................................................... 228

Chapter 6: Future work ............................................................................................ 231

xiv

List of Figures Figure 1. 1. Hypertrophic Scars: (A) appearance of hypertrophic scar (as arrows show).

(B) Joint contracture after burn injury. (C) Radiograph of the same area of scar in part B (Reported from Ref. [4]). ................................................................................2

Figure 1. 2. Schematic of crosslinked polymer network. Mc is the molecular weight between crosslinks and ξ is the mesh size (modified from Chemorheology of Polymers: From Fundamental Principles to Reactive Processing) [24] ....................8

Figure 1. 3. Slab-shaped one dimensional network. The shaded region represents the part of the slab that has not yet been swollen by water. ..........................................11

Figure 1. 4. pH-dependence of silane hydrolysis (Adapted from Sol-gel Science [66]). 29 Figure 1. 5. Modulus change versus temperature from below Tg to flow temperature.

Modes of energy dissipation with each relaxation are shown (taken with permission from Chemorheology of Polymers: From Fundamental Principles to Reactive Processing [24]).......................................................................................................48

Figure 1. 6. Origin of the α’-transition: Propagation of localized smooth twist along the chain. At the starting point of the twist (1) it leaves a transitional mismatch. When the twist continues (2) the mismatch becomes attenuated at large distances from the twist (Adapted from [101]). .....................................................................................50

Figure 3. 1. 1H NMR spectrum of PEG in CDCl3 ...........................................................76 Figure 3. 2. 1H NMR spectrum of 3-glycidoxypropyl trimethoxylsilane (GPS). ............76 Figure 3. 3. 1H NMR of bis(trimethoxy silyl propyl)-PEG with GPS in CDCl3,

compared to PEG and GPS. .....................................................................................77 Figure 3. 4. 1H NMR spectrum of dicarboxylic acid-terminated PEG. ...........................78 Figure 3. 5. FTIR spectrum of bis(triethoxy silyl propyl urethane)-PEG (lower black

line) compared to that of the reagents (upper red line) before reaction...................80 Figure 3. 6. 29Si Solid State NMR spectrum of bis(triethoxy silyl propyl urethane)-PEG

showing band at -46 ppm attributed to T0 (-CH2Si(OC2H5)3). ................................80 Figure 3. 7. 29Si Solid State NMR of amino-functionalized hybrid silica. Silica structures

corresponding to T2, T3, Q3 and Q4 are seen at -59, -68, -102 and -110 ppm, respectively. .............................................................................................................82

Figure 3. 8. Attached polymer random coil around silica particle...................................83 Figure 3. 9. Hydrogen bonding between silanols on the surface of silica and backbone of

PEG. .........................................................................................................................84 Figure 3. 10. Thermogravimetric analysis (TGA) results for different functionalized

silica. ........................................................................................................................86 Figure 3. 11. Moles of different silanes that are attached to 100 g functionalized silica

when treated by different silanes. ............................................................................87 Figure 3. 12. (a) Schematic highlighting the diffusion limitations in DCM1 model. (b)

Schematic of DCM 2 model and reaction between surface and triethoxy silyl propyl urethane-PEO2000...................................................................................................88

Figure 3. 13. 29Si Solid State NMR (CP) for (a) Silica A300, propyl-Silica and vinyl-Silica (b) PEO, PEO 750, PEO 2000 DCM1 and PEO DCM 2 Silica. ...................89

Figure 3. 14. Crosslinked network with dangling chains.................................................94

xv

Figure 3. 15. DSC scans showing the effect of different percentage of PEO2000 dangling chain on the crystal transition in PEG 2000 networks made by a sol-gel reaction (Step crystallization method with 5°C per minute heat rate). ................... 96

Figure 3. 16. 29Si Solid State NMR of PEG 2000 networks with different percentages of PEO 2000 dangling chains. ..................................................................................... 97

Figure 3. 17. Effects of percentage of dangling chain on swelling percentage. (Note the vertical scale in this diagram does not start from zero). ......................................... 99

Figure 3. 18. Percentage of sol fraction in hydrogels with different amount of dangling chain. ..................................................................................................................... 100

Figure 3. 19. Photos of networks at around 22 °C (room temperature) which were made by sol-gel reaction with different amounts of 0.1M HCl. Note the increasing opacity with amount of acidic water used in the synthesis. .................................. 101

Figure 3. 20. Fractionation DSC results of samples formed with an increasing amount of water with 0.1M HCl in networks with PEG2000. ............................................... 102

Figure 3. 21. Dynamic Mechanical Thermal Analysis (DMTA) plots of tan δ and E’ against temperature with change of amount of 0.1M HCl in networks with PEG2000. .............................................................................................................. 103

Figure 3. 22. 29Si Solid State NMR spectra in networks that were synthesized with different amount of 0.1M HCl. ............................................................................. 105

Figure 3. 23. T1, T2 and T3 structures in crosslink area and particles with attached polymer chains. Oxygen, silicon and hydroxyl are not shown. ............................ 107

Figure 3. 24. 29Si Solid State NMR spectra in networks that were synthesized with different amount of acidic water of pH 1 and bis(triethoxy silyl propyl urethane) PEG. ...................................................................................................................... 109

Figure 3. 25. Swelling of hydrogels (synthesized with different amounts of 0.1M HCl) when immersed in pure water. .............................................................................. 110

Figure 3. 26. Changing the number of conformations of a polymer chain during stretching. .............................................................................................................. 110

Figure 3. 27. Percentage of sol fraction in hydrogels synthesized with different amounts of acidic water (0.1M HCl). .................................................................................. 113

Figure 3. 28. DSC results with change in HCl concentrations from 0.001 to 0.2 M in networks with PEG2000. ...................................................................................... 114

Figure 3. 29. 29Si Solid State NMR spectra in networks that were synthesized with different HCl concentration from 0.001M (PEG2000SH1) to 0.2 M HCl (PEG2000SH4). .................................................................................................... 115

Figure 3. 30. Percentage swelling in water of hydrogels which were synthesized with 0.001, 0.01, 0.05 and 0.2 M HCl (PEG2000SH1, 2, 3 and 4). Average error bars are considered from section 3.2.3.1.2, Figure 3. 25.................................................... 119

Figure 3. 31. Percentage of sol fraction in hydrogels which were synthesized with 0.001, 0.01, 0.05 and 0.2 M HCl (PEG2000SH1, 2, 3 and 4).......................................... 120

Figure 3. 32. Changes in the crystal transition temperature of PEG 2000 and its crosslinked networks prepared at different [HCl]. ................................................ 121

Figure 3. 33. DSC results in PEG 400 and bis(triethoxy silyl propyl urethane)-PEG 400 precursor. a) Heating rate 10 °C per min. b) Heating rate 20 °C per min............ 122

xvi

Figure 3. 34. DSC results for in situ silsesquioxane PEG 400 networks synthesized with HCl acid concentration from 0.001 to 0.2 M (PEG400SH1, 2, 3 and 4. The heating rate was 10 °C per min.). .......................................................................................124

Figure 3. 35. 29Si Solid State NMR spectra in crosslinked PEG 400 networks that were synthesized with different acid concentration (from 0.001 to 0.2 M HCl)............125

Figure 3. 36. Percentage of swelling in crosslinked PEG 400 networks that were synthesized with different acid concentration (from 0.001 to 0.2 M HCl)............126

Figure 3. 37. Percentage of sol fraction in crosslinked PEG 400 networks that were synthesized with different acid concentration (from 0.001 to 0.2 M HCl)............127

Figure 3. 38. DCS results for measuring Tg in top and bottom sections in PEG400SH1 sample. ...................................................................................................................128

Figure 3. 39. DSC results (Tg) for PEG 400 networks synthesized with different amount of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and PEG400SW4) (The heating rate was 10 °C per min.)............................................................................129

Figure 3. 40. 29Si Solid State NMR results for PEG 400 networks synthesized with different amount of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and PEG400SW4).........................................................................................................131

Figure 3. 41. Percentage of swelling of PEG 400 networks synthesized with different amount of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and PEG400SW4).........................................................................................................132

Figure 3. 42. Sol fraction in PEG 400 networks synthesized with different amount of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and PEG400SW4)..........132

Figure 3. 43. DSC results in networks with PEG4600 synthesized with HCl concentrations from 0.001 to 0.2 M.......................................................................134

Figure 3. 44. Percentage swelling in water of hydrogels which were synthesized with 0.001, 0.01, 0.05 and 0.2 M HCl (PEG4600SH1, 2, 3 and 4). ..............................135

Figure 3. 45. 29Si Solid State NMR spectra in networks that were synthesized with 0.001, 0.01, 0.05 and 0.2 M HCl (PEG4600SH1, 2, 3 and 4). ..............................136

Figure 3. 46. Step crystallization DSC results of reinforced networks with different percentage of silica. ...............................................................................................138

Figure 3. 47. (a) ‘Ideal’ crystalline structure in linear polymer from polymer solution. (b) Crystalline structure in crosslinked polymer. (c) Crystalline structure in crosslinked polymer with silica. ............................................................................139

Figure 3. 48. 29Si Solid State NMR spectra in networks that were synthesized with different percentage of added silica .......................................................................140

Figure 3. 49. Percentage swelling of reinforced hydrogels in water (calculation with and without silica and average error bars from section 3.2.3.1.2, Figure 3. 25) for different percentage of silica (from 0 to 20%).......................................................141

Figure 3. 50. Sol fraction in reinforced PEG2000 hydrogels that were synthesized with different amounts of silica (from 0 to 20%)...........................................................142

Figure 3. 51. DSC results (Tg) for networks from PEG 400 that were synthesized with different amount of silica (the heating rate was 10 °C per min.)...........................143

Figure 3. 52. 29Si Solid State NMR spectra from PEG 400 networks that were synthesized with different percentage of silica. .....................................................144

Figure 3. 53. Percentage of swelling in reinforced networks (calculation with and without silica) versus percentage of silica. ............................................................145

xvii

Figure 3. 54. . Sol fraction in PEG 400 networks which were synthesized with different amount of silica. .................................................................................................... 146

Figure 3. 55. DSC results (Tg) for networks from PEG 400 with 5% silica which were synthesized with different concentration of HCl (from 0.001M to 0.2M HCl). ... 147

Figure 3. 56. 29Si Solid State NMR spectra in reinforced PEG 400 networks (5% silica) were synthesized with different concentrations of acid (HCl).............................. 149

Figure 3. 57. DSC results of networks in samples PEG2000SW1, PEG2000SW3 and PEG2000SW5 (base and acidic catalysts). ........................................................... 150

Figure 3. 58. 29Si Solid State NMR spectra in PEG 2000 networks were synthesized with different acidic and base catalysts (PEG2000SW1, PEG2000SW3 and PEG2000SW5)...................................................................................................... 151

Figure 3. 59. Percentage of swelling in hydrogels PEG2000SW1, PEG2000SW3 and PEG2000SW5. ...................................................................................................... 152

Figure 3. 60. Sol fraction in PEG 2000 hydrogels PEG2000SW1, PEG2000SW3 and PEG2000SW5. ...................................................................................................... 153

Figure 3. 61. Step crystallization (DSC) in networks PEG2000SH2, PEG2000SH2TS, PEG2000SH3 and PEG2000SH3TS. .................................................................... 154

Figure 3. 62. Step crystallization (DSC) in networks PEG4600SH2, PEG4600SH2TS, PEG4600SH3 and PEG4600SH3TS. .................................................................... 155

Figure 3. 63. 29Si Solid State NMR spectra in PEG 2000 networks that were synthesized with 0.01M HCl (a) (PEG2000SH2 and PEG2000SH2TS) and 0.05 M HCl (b) (PEG2000SH3 and PEG2000SH3TS) (with and without TEOS). ....................... 156

Figure 3. 64. Percentage of swelling in hydrogels PEG2000SH2, PEG2000SH2TS, PEG2000SH3 and PEG2000SH3TS. .................................................................... 157

Figure 3. 65. Percentage of swelling in hydrogels PEG4600SH2, PEG4600SH2TS, PEG4600SH3 and PEG4600SH3TS. .................................................................... 157

Figure 4. 1. 1H-NMR of bis acrylate PEG 2000 after purification ............................... 165 Figure 4. 2. 1H-NMR in CDCl3 of the swollen gel synthesized from the bis acrylate PEG

2000....................................................................................................................... 166 Figure 4. 3. DMTA results (tan δ and E” versus temperature) in bis acrylate PEG 6000

networks with 50% (wt/wt) polymer in methanol solution and 35% (wt/wt) polymer in methanol solution. .............................................................................. 168

Figure 4. 4. Percentage of swelling by water of bis acrylate PEG 6000 hydrogels which were synthesized in 50% (wt/wt) polymer solution in methanol and 35% (wt/wt) polymer solution in methanol. .............................................................................. 170

Figure 4. 5. DMTA result (E’ versus temperature) in reinforced bis acrylate PEG PEG2000 networks PEG2000AS0, PEG2000AS2, PEG2000AS10 and PEG2000AS20. ..................................................................................................... 171

Figure 4. 6. Vibration and rotational movement of the polymer back bone a) below Tg, b) above Tg in pure polymer and c) above Tg when polymer chain movement is hindered with any interaction................................................................................ 172

Figure 4. 7. Thermogravimetric analysis results for A300 silica and calcined-silica. .. 174 Figure 4. 8. Tan δ curves in dry networks PEG2000AS20 and PEG2000AS20C showing

the effect of calcination of silica on the α’-transition and α-transition. ................ 174 Figure 4. 9. DSC results with step crystallization method in PEG2000AS20 and

PEG2000AS20C showing the effect of calcination. ............................................. 176

xviii

Figure 4. 10. DMTA results (E’ and tan δ) in PEG2000AS0, PEG2000AS20, PEG2000AP-S20 and PEG2000AV-S20...............................................................178

Figure 4. 11. DMTA in multi frequency (5, 10, 25 and 50 Hz) mode of experiment in PEG2000AS20.......................................................................................................179

Figure 4. 12. DSC results in PEG2000 networks with different types of silica (PEG2000AS20, PEG2000AP-S20 and PEG2000AV-S20) and without silica (PEG2000AS0). .....................................................................................................181

Figure 4. 13. Percentage of sol fraction in bis acrylate PEG 2000 networks with and without different types of silica (PEG2000AS0, PEG2000AS20, PEG2000AP-S20 and PEG2000AV-S20)...........................................................................................182

Figure 4. 14. Percentage of swelling in bis acrylate PEG 2000 hydrogels with and without different types of silica (PEG2000AS0, PEG2000AS20, PEG2000AP-S20 and PEG2000AV-S20) in water at equilibrium. ....................................................183

Figure 4. 15. Interaction between networks and silica particles with short (a) and long (b) chains on the surface. .......................................................................................184

Figure 4. 16. E’ and tan δ versus temperature in bis acrylate PEG 2000 networks with PEO-silica (PEG2000PEO-S20), PEO2000 DCM2-silica (PEG2000PEO20-S20) and no silica (PEG2000AS0). ................................................................................186

Figure 4. 17. Step crystallization DSC for networks PEG2000AS0, PEG2000PEO-S20 and PEG2000PEO20-S20. .....................................................................................190

Figure 4. 18. Percentage of swelling of hydrogels PEG2000AS0, PEG2000PEO-S20 and PEG2000PEO20-S20 in water at equilibrium. ......................................................191

Figure 4. 19. XRD intensity versus angle (2θ) in neat PEG, PEG2000SWS0, PEG2000AS20, PEG2000AS20C, PEG2000AV-S20, PEG2000APEO-S20 and PEG2000APEO20-S20. .........................................................................................192

Figure 4. 20. a) dry network, b) swollen hydrogel structures. .......................................193 Figure 4. 21. Compression test in swollen hydrogels (PEG2000AS0, PEG2000AS20,

PEG2000AV-S20, PEG2000AP-S20, PEG2000APEO-S20 and PEG2000APEO20-S20) in water at equilibrium points (5 mm/min.). .................................................194

Figure 5. 1. Percentage of swelling of hydrogels PEG2000AS0, PEG2000AS20, PEG2000AV-S20, PEG2000AP-S20, PEG2000APEO-S20 and PEG2000APEO20-S20 in water. All calculations were done based on mass of polymer (PEG).........202

Figure 5. 2. Amphiphilic silicone rake copolymer GP226 molecular weight distribution (GPC). Four fractions of amphiphilic rake silicone copolymer were separated and analyzed to give the individual curves...................................................................204

Figure 5. 3. 1H NMR of amphiphilic rake silicone copolymer (Fraction 1) in CDCl3. .205 Figure 5. 4. DSC of amphiphilic rake silicone copolymer GP226. ...............................207 Figure 5. 5. DMTA of swollen PEG2000AS0 containing amphiphilic rake silicone

copolymer GP226. .................................................................................................207 Figure 5. 6. DSC results in PEG2000AS0 before and after swelling with 14 and 26% of

silicone copolymer. ................................................................................................209 Figure 5. 7. GPC chromatograms of pure silicone copolymer and supernatant liquid of

silicone copolymer on top of the gel......................................................................210 Figure 5. 8. GPC chromatograms of pure silicone copolymer and the extracted silicone

copolymer from the gel. .........................................................................................211

xix

Figure 5. 9. Ultimate percentages of swelling of PEG2000 gels (UV cured) in silicone copolymer with different silica and without silica. ............................................... 212

Figure 5. 10. Ultimate percentages of swelling of gels PEG2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4 when immersed in amphiphilic silicone copolymer.............................................................................................................. 213

Figure 5. 11. Ultimate percentages of swelling of PEG2000 gels which were synthesized (sol-gel method) with different concentration of acidic water and immersed in amphiphilic silicone copolymer. ........................................................................... 214

Figure 5. 12. Ultimate percentages of swelling of PEG2000 gels which were synthesized (by a sol-gel method) with different percentage of dangling chains in amphiphilic silicone copolymer. ............................................................................................... 215

Figure 5. 13. Ultimate percentages of swelling of PEG2000 gels which were synthesized (sol-gel method) with different percentage of silica when immersed in amphiphilic silicone copolymer. ............................................................................................... 217

Figure 5. 14. Ultimate percentages of swelling of PEG4600 gels (PEG4600SH1, PEG4600SH2, PEG4600SH3 and PEG4600SH4) when immersed in silicone copolymer at 50oC and at Room temperature (RT). ............................................. 217

Figure 5. 15. Ultimate percentages of swelling of PEG400 gels which were synthesized (sol-gel) with different amount of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and PEG400SW4) in silicone copolymer....................................... 218

Figure 5. 16. Swelling percentage in fraction 3 and GP226 at gels (PEG2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4). ............................................ 219

Figure 5. 17. 1H-NMR spectrum of fraction three of GP226 in D2O with 0.3% pyridine for silicone concentration measurement during desorption. ................................. 221

Figure 5. 18. Standard calibration curve in the CH3-Si (peak a) compared to area under curve of peak p (pyridine) as unity. ...................................................................... 222

Figure 5. 19. Amount (normalized to starting weight of swollen gel in fraction three) of released silicone copolymer based on CH3-Si (peak a in Figure 5. 17) from gels G2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4 into D2O. ......... 223

Figure 5. 20. Standard calibration curve in PEG 2000 Da (peak c) compared to area under curve of peak p (pyridine) as unity. ............................................................ 224

Figure 5. 21. Amount (normalized to starting weight of swollen gel in fraction three) of released silicone copolymer based on PEO and PEG signals in the 1H NMR from PEG2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4 gels into D2O................................................................................................................................ 225

Figure 5. 22. Amount (normalized to starting weight of dry network) of PEG signals in the 1H NMR from a blank PEG2000SW4 hydrogel (without fraction three of silicone) into D2O.................................................................................................. 226

xx

List of Tables Table 1. 1 Exponent n of the power law and mechanism of drug delivery system of

different geometry [25, 29]. .....................................................................................12 Table 2. 1. Quantities of reagents used for in situ silsesquioxane PEG networks...........65 Table 2. 2. Quantities of reagents used for in situ silsesquioxane PEG2000 networks

with different percentage of dangling chain ............................................................67 Table 2. 3. Quantities of Reagents Used for in situ silsesquioxane PEG Networks with

silica .........................................................................................................................68 Table 2. 4. Quantities of reagents used for bis acrylate PEG2000 networks with and

without silica............................................................................................................69 Table 3. 1. Molecular weight between two crosslink junctions I: theoretical and II:

calculated. Mesh size is based on Mc values in hydrogels (synthesized with different amounts of 0.1M HCl) when immersed in pure water............................111

Table 4. 1. Strength and Strain at Break in Swollen Hydrogels (PEG2000AS0, PEG2000AS20, PEG2000AV-S20, PEG2000AP-S20, PEG2000APEO-S20 and PEG2000APEO20-S20).........................................................................................195

Table 5. 1. Ratio of proton in CH3 in PDMS to proton in CH3 in PEO.........................205

1

Chapter 1: Introduction

1.1 Introduction

Chronic wound treatment is a very serious issue and challenge for an ageing

population. If chronic wounds are not healed at an early stage, treatment is very costly

and lack of treatment in very severe cases may lead to amputation or even death. For

example in the United States there are over 2.8 million patients who suffer from chronic

wounds per year and the cost of treatment is up to several billion dollars per year [1].

Acute wounds are common to the entire population and are caused by surgical incisions

and traumatic injuries such as lacerations, abrasions, tearing, penetrations, bites and

burn injuries. These injuries can be deep and cause damage or even loss of muscles,

blood vessels and bones. The most severe and common form of trauma are wounds that

are caused by burns and thermal injuries. Burns may be superficial or deep injuries and

classified as first, second and third degree [2]. According to the National Center for

Injury Prevention and Control in the United States in each year around two million fire

accidents are reported that result in 1.2 million people with burn injuries. More than

100,000 casualties suffer from moderate and severe burn and need hospitalization.

Approximately 5,000 patients die each year with burns-related injury [3].

In severe burns and cuts after or during wound healing excessive scarring may

occur in the injury area. Scar formation is a normal part of the healing process which in

some cases leads to a very thick skin layer. The most serious burns or damaged tissue

produce worse and thicker scar tissue. Treatment of scars that cause serious issues for

patients costs around four billion dollars per year in the United States [4]. There are two

types of scars which are caused by collagen overproduction in the wound area. The first

type is hypertrophic scars [5, 6]. The appearance of this type of scar is thick, rough,

irregular, raised and red and does not grow beyond the edge of the original wound [7].

In addition to the undesirable cosmetic effect, these patients suffer from ongoing

tightness, redness and itchiness in the scar area as well as some difficulties in movement

when the scars occur in joints such as elbows and knees (Figure 1. 1) [4].

2

Figure 1. 1. Hypertrophic Scars: (A) appearance of hypertrophic scar (as arrows

show). (B) Joint contracture after burn injury. (C) Radiograph of the same area of

scar in part B (Reported from Ref. [4]).

The other type of scar is a keloid scar, where the scar proliferates beyond the

wound border. Much of the literature on both keloid and hypertrophic scars does not

accurately clarify differences between these two types of scars [7]. Keloid and

hypertrophic scars both cause several severe issues to patients such as physiological as

well as psychological problems particularly in children [5]. For tackling these kinds of

scars, numerous therapies have been developed.

3

1.2 Different Methods of Hypertrophic Scar Treatment

In all methods of treatment it is not possible to remove all scars completely and

traces of scar always remain. The available therapies include surgical, non-surgical and

combined methods.

In surgery, the final results of scar removal are difficult to predict. The results

depend on a variety of factors, for example the surgeon’s skill and healing ability of

patients. In surgery a secondary, non-surgical method of therapy can bring better results

[8].

There are several methods of non-surgical therapy. These methods include

occlusive dressing, compression therapy, intralesional steroid injections, laser treatment,

radiation therapy, interferon therapy, bleomycin, 5-fluorouracil, cryotherapy and

silicone therapy [6, 7, 9-11]. Each method of therapy provides a particular advantage,

however, when active agents are to be delivered to scars, using delivery techniques such

as gel-sheet takes advantage of their usefulness as drug delivery vehicles [12]. In some

cases of silicone gel scar therapy, the treatment must be applied over rather long periods,

typically up to 12 hours and in some exceptional cases 24 hours per day [11-15], for

several months with times up to 12 months being necessary in some cases to produce

remediation [11, 14, 15]. In this prolonged therapy, conventional methods of application

of an active agent such as using directly as an ointment can be less effective, rather

expensive, as well as difficult to use. Gel-sheet methods can be beneficial in regard to

effectiveness, easy application and cost-effective since a controlled amount of active

agent may be released [12].

In this research, silicone therapy will be considered as a treatment approach, and

the majority of the investigations in this research will be focused on development of a

delivery system for a low molar mass amphiphilic silicone copolymer.

1.2.1 Silicone Therapy

At the moment, silicone sheet for hypertrophic scar therapy is commercially

available [14]. Previous studies have shown silicone therapy is one of the methods that

has fewer side effects compared to other methods [5, 16]. Silicone is used as silicone

4

sheets and patches and in the case of burn victims it is used under pressure garments to

cover the entire scar area to make the therapy as effective as possible [11, 15, 16].

The mechanism of silicone therapy in hypertrophic scar remediation is

controversial [5, 11] and the mechanism of how silicone sheets affect the hypertrophic

scar is not proven yet [14]. According to some of the studies it is believed that silicone

sheet under pressure garments makes a barrier to keep moisture and oxygen in the area

of scars [14, 16]. In 1985, Quinn et al, [16] showed pressure has no effect on the

alteration in scar temperature and oxygen level in the scars. However, it was found that

hydration of scar and skin was changed with silicone sheets. This affects scars greater

than normal skin since scars lose water faster than normal skin. Beranek mentioned that

hydration of the Stratum Corneum of the skin increased permeability for water- soluble

compounds such as soluble proteins in direction of the skin surface. This phenomenon

was believed to accelerate hypertrophic scar reduction [16]. Moreover, Sawada

suggested that hydration is the main effect of the silicone sheet therapy method and the

presence of silicone does not have essential medical effects on the scars [16, 17]. Chang

and co-workers supported this idea; they suggested that hydration drastically inhibited

proliferation of fibroblasts [16].

However, Quinn suggested that the low molecular weight silicone could diffuse

through the Stratum Corneum and could remediate the structure of scars [16]. This

opinion is supported by Shigeki who showed silicone-related compounds in rat skin,

human axilla skin and hypertrophic scars in an in-vitro test [16]. In 2005, George and

co-workers found linear oligomeric silicone species that terminated with hydroxyl

groups were present as minor components of commercial silicone gel sheets. Further it

was found that these amphiphilic molecules were able to penetrate through the Stratum

Corneum [5]. In this research they used ATR-FTIR (Attenuated Total Reflection

Fourier-Transform Infrared) spectroscopy to measure diffusion coefficient and analyzed

the molecular weight of silicone oligomer with MALDI-MS (Matrix Assisted Laser

Desorption Ionization Mass Spectrometry) which showed the hydroxyl-terminated linear

silicone oligomers’ mass was up to 2100 Da [5].

5

1.2.3. Amphiphilic Silicone Rake Copolymer Therapy

In 2005, Washington H. Sanchez in his PhD research at Queensland University

of Technology (QUT) showed that a commercial amphiphilic silicone rake copolymer

that contains silicone backbone and poly(ethylene oxide) methyl ether side chains

(equation 1.1) migrates through Stratum Corneum and down-regulates fibroblast

production. This suggested that ultimately hypertrophic scars could be shrunk, so

providing a superior therapy. The backbone of this copolymer is hydrophobic

poly(dimethylsiloxane), however, the side chains of the copolymer are hydrophilic

poly(ethylene oxide) (PEO), so this hydrophobic-hydrophilic rake copolymer shows

amphiphilic behavior.

(1.1)

In 2007, Emily Lynam in her Honours research at QUT confirmed that this

amphiphilic silicone rake copolymer decreased collagen production. In this research it

was shown that the amphiphilic silicone rake copolymer has lower collagen production

compared to normal PDMS silicone oligomer (polydimethylsiloxane) (equation 1.2).

These outstanding effects of amphiphilic silicone rake copolymer on reduction of

collagen production has resulted in this investigation of a delivery system for this type

of silicone copolymer to make therapy easier as well as more effective over a shorter

time period than current silicone gel therapies [12].

(1.2)

6

1.2.3. Delivery System for Amphiphilic Silicone Rake Copolymer

The research in this thesis has been focused on developing a cost-effective gel

which has the ability to carry an amphiphilic silicone rake copolymer and then deliver it

when applied to the skin. Poly(ethylene glycol) (PEG) networks are biocompatible, not

very expensive and have the ability to carry other drugs which can be used for wound

healing. The principal reason PEG was chosen as a network was the expected

compatibility between PEG chains and the PEO side chain of the amphiphilic silicone

rake copolymer. It was also recognized when designing the crosslinking system that a

practical network requires good mechanical properties and silica is often used as

reinforcement in elastomers. To achieve both this and the crosslinking of the network, a

novel approach using in situ generation of silsesquioxane crosslink sites for the PEG

molecules has been researched. In the rest of this thesis several methods of PEG

network preparation (synthesis) such as reinforced PEG networks by a sol-gel method of

synthesis will be discussed.

1.3 Networks as A Drug Delivery System

Over the past several decades, network technologies have developed in many

biomedical areas including controlled drug delivery. Since the first hydrogel was

synthesized by Wichterle and Lim in 1954[18], the growth of hydrogel applications has

occurred in many areas such as food industries, biomedical implants and

pharmaceuticals with more recent applications in different technology such as

biosensors [19-21].

A definition of a hydrogel is a polymeric network that is able to absorb and

retain a large amount of water, but it remains insoluble in the solvent due to chemical or

physical crosslinking of the polymer chains [19, 22].

The amount of water that is soaked up into a hydrogel highly depends on the

level of hydrophilicity of the polymer and the density of crosslinking [19, 20, 22]. The

hydrophilic properties of networks produce many outstanding physicochemical

properties that bring advantages for drug delivery applications. For example, hydrogels

are very good candidates for uptake of proteins and DNA due to their good hydrophilic

interactions which can prevent denaturation of their structures [19]. For achieving

7

uptake and delivery of proteins and other active agents by networks, the three-

dimensional structure, crosslinking nature and interaction between the polymer in the

network and the swelling agents have to be well understood [19, 22].

1.3.1 Structures of Networks

Properties of networks depend on the type of polymers, crosslink density and

crosslink nature. Materials selection and network fabrication controls the rate, mode and

mechanisms of swelling into, retention by and release from networks [19]. There are

several important criteria and variables for network selection and design. For example,

the design criteria are [19]:

• Regime of small molecule diffusion (i.e. if Fickian or not)

• Gelation mechanism and conditions

• Structural properties

• Biocompatibility

and the design variables are [19]:

• Molecular weight and size of both swelling agents and polymers

• Crosslink density

• Polymer-swelling agent interactions

• Mechanical strength of polymer

• Cytotoxicity of hydrogels

The diffusion properties of a network control the rate of uptake and release. The

diffusion coefficient is determined by the molecular size of swelling agents and

characteristics of the network. The variables involved with diffusion coefficient in

networks are the crosslink density and mesh size [19].

1.3.1.1 Nano-Structure of Crosslinked Networks

Network swelling and de-swelling, mechanical properties and applications depend on

the hydrophilicity as well as nanostructure of crosslinked polymer network [19, 23, 24].

There are three critical parameters that control the nanostructure [25]:

1. Polymer volume fraction in the swollen state, υ2,S,

8

2. Number average molecular weight between two crosslinks junction, Mc,

(Figure 1. 2).

3. Mesh size in networks, ξ

Figure 1. 2. Schematic of crosslinked polymer network. Mc is the molecular weight

between crosslinks and ξ is the mesh size (modified from Chemorheology of

Polymers: From Fundamental Principles to Reactive Processing) [24]

In non-porous networks (ie. those that do not have other non-crosslinked

polymer or porogen added to make micro-voids and so increase porosity of the network)

the structure is quite uniform, and the mobility and rate of diffusion of swelling agents

are controlled by the amount of swelling material in the networks, flexibility of chains

and distance between crosslinks [19].

The polymer volume fraction in the swollen gel is a measure of the swelling

agent that gels hold in their structure at the equilibrium swelling point [19, 23].

ρρ

ρν

21

2,2 1

11gelswollen of Volume

Polymer of Volume+

====QQVgel

Vp

mS

(1.3)

9

where Q is volumetric swollen ratio, ( ρ1) and ( ρ2) are density of the swelling agent and

polymer density respectively and (Qm) is the mass swollen ratio.

The number average molecular weight between two crosslink junctions, Mc, can

be calculated by several different theories such as Flory-Rehner or rubber elasticity

theories [19, 23].

Mesh size in networks, ξ, can be obtained theoretically or experimentally with

laser light scattering, electron microscopy, mercury porosimetry, rubber elasticity

measurements or equilibrium swelling experiments [19, 23]. Mesh size is controlled by

crosslink density, chemical structure of monomers and crosslinker that are used to make

the gel and external stimuli such as pH, temperature and ionic strength [19]. Mesh size

calculation is important for understanding the physical properties of networks, because it

has an effect on mechanical properties and strength and high influence on diffusion into

and release of molecules from networks [19, 23]. The mesh size can be calculated when

the gel is fully swollen at equilibrium state [26]:

121

32,

2 n cs

r

C M lM

ξ υ − ⎛ ⎞= ⎜ ⎟

⎝ ⎠ (1.4)

where l is polymer bond length between two adjacent atoms (C-C) along the backbone,

Cn is Flory characteristic ratio (Cn= 4.0 for PEG), where Mr is the molecular weight of

the repeating unit.

1.3.2 Swelling and Release Mechanisms in Networks

Models of gel swelling and release have been developed to predict both swelling

and release phenomena as a function of time. These models play very important roles in

designing the release of active ingredients, because rates of drug release have direct

impact in treatment [19].

There are three major categories for models of uptake and release in networks

[25]:

10

1. Diffusion controlled:

This mechanism is widely used to describe drug release and swelling in

networks. Fick’s law of diffusion with either constant or variable diffusion coefficients

is used in this model. The drug diffusion is determined by using free volume,

hydrodynamic or obstruction-based theories [19, 27].

2. Swelling Controlled:

Swelling-controlled release happens when swelling agent diffusion is faster than

network swelling. In this mechanism, the interface movement of the rubbery and glassy

phase boundary in network is detected [19]. In this system the release rate is controlled

by two factors. The first one is the front separation of the rubbery (swollen part) region

and the glassy state that the solvent or biological fluid has not yet diffused into. The

other factor is the velocity of the polymer-fluid interface [23, 28]. If the rate of release

of the solute is faster than the rate of swelling by the solvent (network chain relaxation

process) [37] this results in a time-independent release rate. This type of diffusion is

named Case II transport and has zero order release kinetics. The swelling agent behaves

as a plasticizer and lowers the glass transition temperature (Tg). This change in the

polymer from the glassy to the rubbery state helps the relaxation of network chains and

ultimately increases the mobility of chains [29, 30]. The drug uptake or release occurs

via the rubbery region in networks.

3. Chemically Controlled

This mechanism of release happens when delivery of drug is caused by chemical

reactions. There are two major types of chemically controlled release system [23]. The

first type of release is an erodible drug delivery system. Drug release occurs due to

degradation or dissolving of the networks. Network erosion takes place simultaneously

with drug release, however, by decreasing the dimensions of the network because of

erosion, the drug delivery rate can change [23].

1.3.2.1 Uptake and Release Based on Diffusion

The loading of active drugs into a network is as important as their release. In the

post-loading method, the uptake of drugs takes place after network formation [19].

11

When gels and swelling agents are inert and there is no chemical interaction

between them, the major driving force for drug loading and release is the chemical

potential for diffusion. The empirical equation describing this process over typically

Figure 1. 3. Slab-shaped one dimensional network. The shaded region represents

the part of the slab that has not yet been swollen by water.

50% of the uptake or release for the simple case of a slab-shaped network immersed in a

solution (Figure 1. 3) is equation 1.5 [31]. This is a particular solution to Fick’s law of

diffusion.

1 2

22tM DtM Lπ∞

⎛ ⎞= ⎜ ⎟⎝ ⎠

(1.5)

where Mt is weight increase at t time, M∞ is mass at equilibrium, 2L (h) is thickness of

network and D is diffusion coefficient that is independent of drug concentration. In early

stage of swelling (Mt/M∞≤0.5) the plot is linear and equation (1.5) may be used to

calculate D [31].

A power law model is a more comprehensive and relatively simple equation to

describe drug release in the general form [29]:

ntM ktM ∞

= (1.6)

12

where k is a constant that is related to diffusion coefficient and network dimensions [25,

29, 32]. Here, n is the release exponent that depends on the mechanism of swelling and

release and the geometry of the sample (Table 1. 1).

Table 1. 1 Exponent n of the power law and mechanism of drug delivery system of

different geometry [25, 29].

Exponent, n Drug Release Mechanism

Thin Film Cylinder 0.5 0.45 Fickian Diffusion

0.5<n<1.0 0.45<n<0.89 Anomalous Transport 1 0.89 Case-II Transport

1.3.3 Equilibrium Swelling Theories

The driving force for swelling of and release from networks is chemical

potential. In general, chemical potential in network system is a multi-variable function

[33]:

( ), , , ,{ }if V T yμ π χ= (1.7)

where π is the total osmotic pressure, V is the volume, T is the absolute temperature, χ is

the network-solvent interaction parameter and{ }iy is the network structure parameter

[33].

During the swelling process, polymer networks are deformed. This deformation

raises the stress on polymer chains in the networks and it affects the rate of further

swelling. This phenomenon has been studied by Flory and Rehner, and in the classical

Flory-Rehner theory the elastic free energy is described [34]. According to their study,

with any increase in the degree of swelling in gels, the swollen networks build up higher

tension. In other words, the theory is based on two opposing phenomena, a balance

between the elastic forces of polymer chains and the thermodynamic compatibility of

polymer segments and the solvent molecules that dictate the degree of gel swelling [23].

13

Gee (Cited by Shenoy [34]) demonstrated that Flory-Rehner theory works reasonably on

the swelling of rubbery gels in good solvents (swelling agents).

The free-energy changes are in the free-energy of mixing (ΔGm) and in the free-

energy of elastic deformation (ΔGel) [35-38]. The total free energy change of swollen

gel is shown:

el mG G GΔ = Δ + Δ (1.8)

These relationships are used when determining the swelling at equilibrium and

based on this equation crosslink density (molecular weight between two crosslinking

junctions) and mesh size can be calculated.

1.4 Synthesis of Functionalized Poly (ethylene glycol) For Networks

1.4.1 Poly (ethylene glycol) (PEG)

Poly (ethylene glycol) or PEG is one of the polymers that has been approved by

FDA as a completely biocompatible polymer for internal consumption [39]. PEG has

therefore been used in a wide range of biomedical and biotechnical applications. PEG is

a polyether which contains oxygen atoms in the polymer backbone (equation 1.9) [39]:

(1.9)

Although the structure of PEG is very simple, this macromolecule is important in

many biotechnical and biomedical areas [39]. Primarily, this polymer is effective at

excluding other polymers from its presence when in an aqueous environment. This

property reduces protein rejection, formation of two-phase systems with other polymers,

non-immunogenicity (immunogenicity is the ability of antigen to elicit immune

response) and non-antigenicity. Also PEG is not toxic and harmful for active proteins

and cells, although it interacts with cell membranes. PEG has the following properties

[39]:

1. Soluble in cold water, toluene, benzene and methylene chloride.

2. Insoluble in warm and hot water, diethyl ether, hexane and ethylene glycol.

3. Highly mobile and large exclusion volume in water.

14

4. Nontoxic and biocompatible (approved by FDA).

5. Causes cell fusion in very high concentration.

6. Solubilizes other molecules.

7. Facilitates movement of molecules across cell membranes (according to

Beckman cited by Milton [39])

Because of the above properties the networks that are made from poly (ethylene

glycol) can be applied as wound healing materials.

All the networks are either chemically or physically crosslinked polymers. In

most of the cases, hydrogels based on PEG are chemically crosslinked polymer

networks. In PEG structure (equation 1.9) hydroxyl groups (OH) are available at both

chain ends. These hydroxyl groups provide chemically active sites for further reaction to

change hydroxyls to other higher activity groups such as acrylate or alkoxysilane which

are able to react and make three dimensional networks and crosslinked polymers.

1.4.2 Synthesis of Different Terminally Functionalized PEG

PEG has hydroxyl groups at the end of the backbone. These hydroxyl groups are

not sufficiently active to chemically synthesise networks directly, without any

functionalization. For synthesizing networks, the presence of accessible active

functional groups such as acrylate, allyl and silane in the backbone, or as the end group

of the backbone, is essential. From this perspective, hydroxyl groups in PEG are

chemically active sites to do functionalization reactions as described in the following

sections.

1.4.2.1 Synthesis of Bis (trialkoxy silyl propyl)-PEG

Synthesis of silane terminated PEG may take place by reaction between

hydroxyl end group and suitable active groups in the organic end of organo-silane such

as isocyanate, epoxy ring and amine. In some cases such as amine the hydroxyl group

must change to another precursor active group. The precursor which is suitable for

amine is carboxylic acid. The silane group is very susceptible to the presence of water,

as it can be hydrolysed and react with other silane groups. To tackle this issue, the PEG

functionalization reaction must not produce any water as a by-product. This restricts the

possible reaction and purification strategies.

15

Among the silanes that can be used are:

(a) (3-Glycidyloxypropyl)trimethoxysilane (GPS)

(b) 3-Triethoxysilylpropylamine (APTES)

(c) 3-(Triethoxysilyl)propyl isocyanate

1.4.2.1.1 Reaction of (3-Glycidyloxypropyl)trimethoxysilane (GPS) with PEG

(3-Glycidyloxypropyl)trimethoxysilane (GPS) contains both alkoxysilane and an

epoxy ring at the end of a short organic tail (equation 1.10).

(1.10)

Epoxy rings can react with primary and secondary amine, anhydride [40] and

anion groups (ie. fairly strong base) (equation 1.12.) [41, 42]. Equation 1.11 shows the

anion formation from the reaction of an alcohol with a metal hydride.

(1.11)

PEG has hydroxyl (OH) end groups that are able to be changed to the dianion.

These dianion groups react with the epoxy group at the end of GPS and the final product

is silane-capped PEG.

(1.12)

1.4.2.1.2 Reaction of 3-triethoxysilylpropylamine (APTES) with PEG

3-Triethoxysilylpropylamine (APTES) contains a primary amine (-CH2-NH2)

group that is available for functionalization by using the amide reaction with carboxylic

acid groups (-CH2-COOH).

16

OSi NH2O

O

(1.13)

The amide reaction is an equilibrium reaction with water as a by-product

(equation 1.14).

(1.14)

Water generation in the amide formation reaction causes two major problems.

Firstly, water slows down the rate and drops the efficiency of the reaction. The second,

water causes hydrolysis of ethoxysilane (CH3-CH2-O-Si) and initiates the condensation

reaction that leads to both chain extension and ultimately premature gelation and

crosslinking reactions. To avoid premature gel formation, water as a by-product must be

extracted out chemically before having any chance to react with ethoxysilane.

To tackle these issues, coupling reagent such as 1-ethyl-3-(3-

dimethylaminopropyl) carbodiimide (EDC) (equation 1.15) can be used. This reagent

(EDC) reacts with the carboxylic acid to activate it for reaction with amine group [43].

(1.15)

For synthesis of bis(trialkoxy silyl propyl)-PEG with amide linkage, in first step

hydroxyl groups (OH) at both ends of PEG must be changed to carboxylic acid groups (-

CH2-COOH). To achieve this, PEG is modified with succinic anhydride [44]

(1.16)

17

(1.17) Amide linkage group is made by reaction between carboxylic acid (-CH2-

COOH) and primary amine. Pure dicarboxylic acid-terminated PEG and 3-

triethoxysilylpropylamine (APTES) reaction produces bis(triethoxy silyl propyl amide)-

PEG. For high conversion amide reaction, carboxylic acid and primary amine react in

the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as a coupling

reagent.

OR1-NH-C-NH-R2

R1-N=C=N-R2H

+

R1-NH-C=N-R2

H+

R'-NH2

R-C-

O

O-C-R

OR-C-O

O

R1-NH-C-N-R2

R-C-O

O-O

R1-NH-C-NH-R2R'-NH2

R-C-NH-R'

O

H+DMAP/

H+DMAP/

R'-NH2

R-C-NH-R'

O OR1-NH-C-NH-R2

OR1-NH-C-NH-R2

C CN

CCCN C-R

H3C

H3C

O

R-C-O

O-

R-C-O

O

R1-NH-C=N-R2

+

Hydrolysis

+

+

+

Rapid Reaction

Slow Reaction

++

(1.18)

18

In equation 1.17 carbodiimide changes to urea, without producing water as a by-

product, as an amide linkage is made. This reaction needs p-toluenesulfonic acid

(PTSA) and 4-(dimethylamino)pyridine (DMAP) complex as catalyst and 30% excess 1-

ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) is added in dry and inert

atmosphere [45].

The mechanism of amide reaction in the presence of 1-ethyl-3-(3-

dimethylaminopropyl) carbodiimide (EDC) is shown in reaction scheme 1.18 above [43,

45].

1.4.2.1.3 Reaction of 3-(triethoxysilyl)propyl isocyanate with PEG

Reaction between isocyanate and hydroxyl groups is well-known as the urethane

reaction.

(1.19)

This reaction can take place between hydroxyl group in poly (ethylene glycol)

and isocyanate group in 3-(Triethoxysilyl)propyl isocyanate.

(1.20)

An advantage of the urethane reaction is that it does not produce any by-product,

which means the silane group can be protected for the next step of reaction. Also this

reaction is straight-forward and final product does not need much purification except

solvent evaporation and catalyst sublimation. The isocyanate groups are extremely

sensitive to moisture and have complete reaction with water to make carbon dioxide

(CO2) and primary amine [46]

Urethane reactions need catalysts for promoting the reaction rate. There are two

groups of catalysts in urethane linkage reactions. The first one is organometallic

compounds which are Lewis acid catalysts (equation 1.21) [47, 48] such as dibutyltin

dilaurate or bismuth octanoate.

19

(1.21)

The urethane reaction mechanism in the presence of Lewis acid catalysts is

uncertain, despite numerous investigations on mechanisms and kinetics of reaction. In

equations 1.22 and 1.23 two different proposed mechanisms are shown that illustrate

complications in both mechanisms [49].

R' N C OMX2

R' N C O

R' N C O

MX2

MX2

R" OH + MX2 R" O H

MX2

Mechanism-1

Mechanism-2

R' N C O

MX2OH

R"

R"-OH

R'-NCO

R' NH C O

OMX2

R"

R' NH C O

OMX2

R"

R' NH C

O

O R"+MX2

(1.22)

(1.23)

20

The second type of catalyst is a tertiary amine (equation 1.24), such as

dimethylcyclohexylamine [48]. Again there are two possible mechanisms.

It has been proven that steric hindrance in structures of tertiary amine catalysts

affects their activity. The tertiary amine catalysts that have low steric hindrance on the

nitrogen atoms and on the lone pair electrons promote the urethane reactions. Also steric

hindrance effects of tertiary amine catalysts play an important role on formation of urea

in the same way as the urethane linkage [48].

(1.24)

1.4.2.2 Synthesis of Bis acrylate PEG

To form the bis acrylate PEG an esterification reaction between the terminal

hydroxyl groups and acryloyl chloride in the presence of a tertiary amine is used

(equation 1.25).

21

(1.25)

A by-product of this reaction is hydrogen chloride which reacts with

triethylamine to produce a salt [50, 51].

1.4.3 Synthesis of Networks from Functionalized PEG

1.4.3.1 Synthesis of Networks from Bis(trialkoxy propyl)-PEG (Sol-gel Reaction)

Reaction between silane groups at both ends of PEG makes one, two or three

dimensional structures that are either chain extended or crosslinked parts of the polymer

network. The reaction takes place in the presence of water and at low pH via hydrolysis

and condensation mechanisms (sol-gel reaction) [52-55]. The crosslink structures

depend on chemical connections of the silicon atoms to other atoms. The mesh size in

the networks depends on these crosslink structures.

(1.26 a)

22

SiPEG

SiPE

G

SiPEG

SiPEG

SiPEG

SiPE

G

SiPEG

(1.26 b)

The rate of reaction can be controlled by diffusion due to the end group reaction

between polymer chains. Diffusion also controls the final structure of networks in

crosslinked samples. In other words, during progressive silane end group condensation

reaction and development of two-(T2) or three-dimensional (T3) network structures,

diffusion of non-reacted silane end groups can be restricted due to increased viscosity

during formation of network structures (equation 1.26 b)). This movement restriction

can be considerably increased when one end of the bis(triethoxy silyl)-polymer chain

has already been reacted. The detailed chemistry is given in Section 1.5.2 below.

1.4.3.2 Synthesis of Networks from Bis acrylate PEG

Unsaturated monomers or macromonomers such as bis acrylate poly (ethylene

glycol) can carry out free radical reactions to make polymer chains or crosslinked

networks [56, 57]. In bis acrylate PEG network formation, a photo-initiator can be used

to generate radicals. The radicals attack the acrylate groups to provide macro-radicals.

These macro-radicals can attack other acrylate groups to form crosslink structures or be

terminated by radical transfer, recombination or disproportionation reactions. The

network structures highly depend on the termination reaction as well as arrangement of

23

polymer chains during crosslinking in solution such as polymer chain entanglements.

The detailed chemistry is discussed in Section 1.5.1 below.

1.5 Mechanisms of Network formation in both Free Radical Polymerization and

Sol-Gel Reactions

1.5.1 Free Radical Polymerization

Free radical polymerization is initiated by reactive species that can generate free

initiator radicals or primary radicals with appropriate energy input. This energy can be

provided by heat, UV or γ radiation and the population of radical species is controlled

by the amount and level of energy.

(1.27)

where I is the initiator, R* is the radical species or primary radical, E is the energy that

is needed for the initiator dissociation (eg hν for photo-initiation) and kd is the rate

constant of the initiator dissociation [57]. The photo-initiator is a compound that

converts absorbed light energy (hν) into chemical energy in the form of initiating

species such as free radicals or cations. As an example, 2,2-dimethoxy-2-

phenylacetophenone and 4,4'-bis(diethylamino)benzophenone are the photo-initiators

which can be activated in a different range of wavelength.

The initiator radicals attack the unsaturated macromonomer, and carbon-centered

macro-radicals are produced as shown below for one acrylate group of the PEG

diacrylate:

(1.28)

where ki is the rate constant of macro-radical initiation. This reaction occurs at both ends

of bis acrylate PEG [57].

24

C O

CHH2C

O

PEG-Acrylate

RC O

HCH2C

O

PEG-Acrylate

+kp

C O

CHH2C

O

PEG-Acry.

R

C O

CHCH2

O

PEG-Acry.

C O

CHH2C

O

PEG-Acry.

R

C O

CHCH2

O

PEG-Acry.

CO

HCH2C

O

PEG-Acrylate

+

C O

CHH2C

O

PEG-Acry.

R

C O

CHCH2

O

PEG-Acry.

CO

CHCH2

O

PEG-Acrylate

kp

(a)

(b)

(c)

(d)

(1.29)

The next step in free radical polymerization is the propagation step which

consists of the growth of the macro-radical by addition of a number of unsaturated

monomer molecules. The number added per initiation event is the kinetic chain length.

Each addition generates a new radical that has the same identity as the previous one

[57]. The network structure is formed when the propagation reaction includes both

acrylate groups of the bis acrylate PEG. A random three-dimensional arrangement of

polymer backbones is a key feature of this network. The rate of propagation reaction is

high due to high value of kp the rate constant of the propagation reaction [57]. However,

the propagation reaction can be slowed down by further development of the network

structure. This is because of the reduced number of the unsaturated monomer units as

well as difficulty of diffusion of reactive macromolecules to find the available monomer

due to three-dimensional network formation.

Polymerization rate also depends on the concentration of initiator. The rate will

increase with the square root of the initiator concentration [57, 58]

( ) [ ][ ]1 2 1 2p p d tR k f k k M I= (1. 30)

25

where Rp is the rate of polymerization, f is the initiator efficiency and kt is the rate

constant of termination.

The last step in free radical polymerization is bimolecular termination [57] with

the annihilation of the radicals by recombination or coupling, reactions when two

macro-radicals or one macro-radical and one primary radical react with each other to

produce one covalent bond (equation 1.31).

(1.31)

In other cases, the hydrogen atom that is located in beta position to a radical

center is transferred to another radical center to neutralize that macro-radical. The

hydrogen radical donor macro-radical changes to carbon-carbon double bond polymer

chain. This type of termination is disproportionation (equation 1.32) [57].

When the concentration of initiator is high enough, radical transfer to initiator

takes place and changes the crosslink structure and chain length. This is because this

transfer stops further crosslinking and joining more bis acrylate PEG to this part of

network. In higher conversions of polymerization in crosslink region, viscosity rapidly

increases due to the three dimensional structures of the networks and increase of

polymer chain segments in crosslink area. This causes a decrease in the rate of

translational diffusion of acrylate PEG in the network which affects the number of un-

reacted polymer chains. These un-reacted chains can change the mechanical properties

26

of polymer networks above and below the melting point of crystalline polymers such as

PEG due to difference in ability of polymer to pack in a crystal when both ends are

chemically bound or only one side is attached in the networks via a covalent crosslink

bond.

C O

CHH2C

O

PEG-Acry.

C O

CHCH2

O

PEG-Acry.

CO

CHCH2

O

PEG-Acrylate

C O

CH

O

PEG-Acry.

C O

CHCH2

O

PEG-Acry.

CO

CHCH2

O

PEG-Acrylate

CH2+

C O

CHH2C

O

PEG-Acry.

C O

CHCH2

O

PEG-Acry.

CO

CH2CH2

O

PEG-Acrylate

C O

CH

O

PEG-Acry.

C O

CHCH

O

PEG-Acry.

CO

CHCH2

O

PEG-Acrylate

CH2+

(1.32)

1.5.2 Sol-gel Reaction in Organic-Inorganic Hybrid Polymer Formation in

Crosslinked Network

According to Chujo [59, 60], Oh [61], Granqvist [62] and Kweon [63, 64], a sol-

gel reaction can be used as a method to form an organic-inorganic hybrid polymer as

either a composite material or a crosslinked material in the presence of tetraethoxysilane

(TEOS) or tetramethoxysilane (TMOS) in water/ethanol solution and an acidic catalyst

such as HCl. This sol-gel reaction can form three dimensional silica and to form this

silica structure inside the polymer bulk (in situ) as a crosslinker, addition of TEOS is

essential. On the other hand, water, ethanol and catalyst ratio changes can alter in situ

silica size and structures. In the absence of TEOS, it can provide controllable in situ

silica (silsesquioxane) structures which ultimately enables control of the organic-

inorganic hybrid polymer properties.

27

1.5.2.1 Sol-Gel Reaction to Form in situ Silsesquioxane as Crosslinker with

Bis(triethoxysilyl)-Polymer

1.5.2.1.1 Sol-Gel Processing Reaction

In sol-gel reactions, metal alkoxide compounds are widely used, eg. tetraethoxy

silane (tetraethyl orthosilicate, TEOS) [65, 66]. Metal alkoxides are precursors in sol-gel

processing, because they react with water in acidic condition (by employing HCl) or in

base catalysis such as with NH4OH. This reaction is termed hydrolysis since the

hydroxyl group is ultimately attached to the metal atom, as shown in equation 1.33 [66]:

(1.33)

where R is CxH2x+1. Hydrolysis reaction takes place by the nucleophilic attack of the

oxygen in the water molecule on the silicon atom in tetraalkoxysilanes or, more

generally, organoakoxysilanes. Hydrolysis becomes faster and complete when highly

active catalysts are employed. Mineral acids and ammonia are the most general catalysts

in sol-gel processing. Other catalysts are acetic acid, KOH, amines, KF, HF, titanium

alkoxides and vanadium alkoxides [66]. Rate of hydrolysis in silane is a minimum at pH

7 and in both acidic (hydronium ion) and base (hydroxyl ion) catalysts, the rate

increases (Figure 1.4) and depends on the strength and concentration of the catalyst.

Temperature and solvent are the second important parameters. Aelion [67] found all

strong acids behaved similarly, whereas weaker acids required longer time for reaction

to achieve the same level of reaction. Studies of the rate of hydrolysis versus

hydrochloric acid concentration [HCl], show the reaction is first-order based on acid

concentration. The other factor that can control hydrolysis and condensation reaction is

the water/Si ratio (r). An increase in the amount of water is expected to promote the

hydrolysis reaction. The catalytic hydrolysis reaction has different order of reaction in

concentration of water [H2O]. Alieon found the acid-catalyzed hydrolysis reaction is

first order in [H2O], while the hydrolysis reaction under base-catalysis is independent of

the amount of water, ie. zero-order [66, 67]. According to equations 1.34 and 1.35, the

relative rates of alcohol or water production of condensation reactions are controlled by

28

r. However, addition of water higher than certain level reduces the concentrations of

both monomer and intermediate, which in turn reduces the condensation rate, ultimately

causing an increase in the gel time.

(1.34)

(1.35)

This hydrolysis can occur fully, whether all R groups are hydrolyzed or partially

hydrolyzed. Two partially hydrolyzed molecules or one hydrolyzed and one metal-

organic molecule can react and link together to make a bigger molecule through a

condensation reaction. This reaction continues to build larger and larger polymer chains

with different structures. Each condensation reaction releases small molecules, such as

water or alcohol. Water and acid or base molar ratios compared to Si can be varied

depending on the desired end product properties and structures. Acid-catalyzed

hydrolysis with low water ratio produces weakly branched polymeric structure,

however, base-catalyzed hydrolysis with high water ratio to Si makes highly condensed

particulate structure. Intermediate conditions between these two extremes produce

different intermediate structures.

Based on pH of reaction, polymerization process is divided in three pH domains

that are: below pH 2, between pH 2 and 7 and above pH 7.

1.5.2.1.2 Mechanisms of Hydrolysis

The hydrolysis reaction of tetraalkoxysilanes and organoalkoxysilanes is

influenced by steric and inductive effects of specific-acid (H3O+) and specific-base

(OH¯) catalyzed reactions. The hydrolysis reaction is considered as bimolecular

nucleophilic displacement reaction or nucleophilic substitution (SN2-Si reactions) [66,

68]. The rate of hydrolysis reaction depends on pH as shown in Figure 1. 4. The rate of

hydrolysis around pH 7 is very slow.

29

Figure 1. 4. pH-dependence of silane hydrolysis (Adapted from Sol-gel Science

[66]).

1.5.2.1.3 Acid-Catalyzed Hydrolysis Mechanism

In acidic conditions, it is possible for the alkoxide group to be very quickly

protonated in the first step. As a result, electron density is withdrawn from the silicon

atom, making it more electrophilic, so the water molecule can easily attack this

electrophilic center. This is favored by a transition state with SN2 type reaction character

in which the departure of the leaving group occurs simultaneously with attacking by the

entering group. This means the water molecule attacks from the rear and gets a partial

positive charge. The protonated alkoxide charge is reduced so making alcohol a better

leaving group. The transition state decays with displacement of alcohol accompanied by

inversion of the silicon tetrahedron [69-71].

(1.36)

30

In this mechanism the rate of hydrolysis is increased by substitution that reduces

steric crowding around silicon. Therefore, electron donating substituents (e.g., alkyl

groups) which can help in stabilizing the developing positive charges may also escalate

the hydrolysis rate. However, to a lesser extent, the silicon acquires little charge in the

transition state.

Deiters, Holmes [69, 70], Keefer and Uhlmann (cited by Brinker [66]) proposed

the other hydrolysis mechanism that involves flank-side attack without inversion of the

silicon tetrahedron. The acid-catalyzed mechanism is the following [71]:

(1.37)

This mechanism depends on both steric and inductive effects. Compared to the

SN2 mechanism, electron-donating substituents have a great effect due to the silicon

acquiring more charge in the transition state.

The third proposed acid-catalyzed hydrolysis mechanism is involved with a

reactive intermediate, the siliconium ion (≡Si+) (although siliconium ion is not easily

generated in solution and has only been obsereved in the gas phase). The alkoxide group

is protonated very rapidly, followed with a slower step in which a siliconium ion is

formed by the removal of alcohol

(1.38)

A water molecule reacts with the siliconium ion and forms a silanol and the

proton is regenerated.

(1.39)

In this mechanism, the reaction has third-order overall kinetics which is

accelerated by electron-donating substituents attached to silicon [66].

31

1.5.2.1.4 Base-Catalyzed Hydrolysis Mechanism

For hydrolysis reaction under basic conditions, in the first step water dissociates

to produce nucleophilic hydroxyl anions (HO¯) very rapidly. After that, the hydroxyl

anion attacks the silicon atom. Iler proposes an SN2-Si mechanism in which nucleophilic

hydroxyl anion displaces alkoxide group with inversion of silicon tetrahedron [65, 66,

70]:

(1.40)

In the same way as the mechanism which was mentioned in acid-catalyzed

reaction, this mechanism is affected by steric and inductive factors. The steric factors

are more important because the silicon acquires little charge in the transition state.

The other mechanism is SN2**-Si or SN2*-Si mechanism which involves a stable

5-coordinated intermediate. This intermediate decays through a second transition state

and any of the surrounding ligands can acquire a partial negative charge. Hydrolysis

reaction occurs only by displacement of an alkoxide anion which is promoted by

hydrogen bonding of alkoxide anion with the water and solvent [66, 72]

(1.41)

The silicon acquires a negative charge in the transition state so that SN2**-Si or

SN2*-Si mechanisms are very sensitive to inductive as well as steric effects. Substituents

such as –OH or –OSi which are electron-withdrawing groups can help stabilize the

negative charge on silicon, in other words, the hydrolysis rate can increase with the

extent of OH substitution. In contrast, electron-donating substituents cause the

hydrolysis rate to reduce. In this mechanism inversion of configuration is not suggested,

the hydrolysis rate may increase with the extent of condensation.

32

In these three mechanisms (SN2-Si, SN2**-Si and SN2*-Si), the hydrolysis

kinetics are expected to be first-order in [OH¯] and second-order with water and silicate

(third-order overall kinetics) for all these three mechanisms Therefore it is not possible

to distinguish between these mechanisms based on the reaction order [72].

1.5.2.1.5 Reaction Rates and Mechanism of Condensation

As mentioned in section 1.5.2.1.1, condensation and polymerization to form

siloxane bonds take place by either an alcohol-producing condensation reaction or a

water-producing condensation reaction. The studies show that a typical sequence of

condensation products is monomer, dimer, linear trimer, cyclic trimer (at high pH),

cyclic tetramer, and higher-order rings. In early studies, Iler described the branching and

crosslinking to form a three dimensional molecular network as the monomer changes

into siloxane chains. He believed that a siloxane network can be obtained under

conditions (temperature, solvents, water and pH) where depolymerization is least likely

to take place. This is because the condensation reactions are irreversible and siloxane

bonds cannot be hydrolyzed once they have formed. Based on the insolubility of silica

under the condensation reaction conditions the siloxane chains cannot undergo

rearrangement into particles [65, 66]. This concept of irreversibility is not widely

supported and the reactions are shown later as reversible processes.

The condensation reaction of silanols can occur with thermal reaction without

any catalyst. Several types of catalyst, not only acid or base, but also neutral salts and

transition metal alkoxides can be employed. The understanding of how catalyst affects

this and the hydrolysis reaction is very difficult and complex. The pH-dependence

suggests that for highly crosslinked systems, protonated and deprotonated silanols are

involved in the acid- and base-catalyzed condensation mechanisms at pH<2 and pH>2,

respectively. Under basic conditions, condensation reactions carry on but gelation does

not occur, and particles are formed after reaching a critical size and become stable

toward gelation due to mutual repulsion effects [66].

1.5.2.1.6 Steric and Inductive Effects in Condensation process

According to Voronkov, the condensation rate of triorganosilanols decreases

with increase in the length or branching of the alkyl chain (e.g. bis(triethoxy silyl)-PEG)

33

or if aromatic groups are present. In tetrafunctional alkoxides (e.g. TEOS) which is used

in sol-gel processing it is expected that the substituents which increase steric crowding

in the transition state can retard the rate of condensation reaction. Voronkov also says

that the rate of condensation increases with an increase in the number of silanols on the

silicon atom due to increasing silanol activity [73].

Electron-donating alkyl groups reduce the acidity of the corresponding silanol. It

significantly influences the pH-dependence of the condensation mechanism. However,

electron-withdrawing groups such as –OH or –OSi increase the silanol acidity and the

minimum condensation rate for oligomeric species occurs at pH 2. Consequently, both

hydrolysis and condensation in organoalkoxysilanes (e.g. triethoxy silyl poly (ethylene

glycol)) can be controlled with acid- or base-catalysts and depend on x, which is the

number of alkyl groups in organoalkoxysilanes [R’xSi(OR)4-x].

Inductive effects are important as well, Voronkov state that in acid-catalyzed

condensation of dialkysilanediol or organoalkoxysilane with a long alkyl chain, steric

effects predominate over inductive effects [73].

1.5.2.1.7 Acid-Catalyzed Condensation

It is believed that acid-catalyzed condensation mechanism involves a

protonataed silanol species. The protonated silanol causes the silicon to be more

electrophilic, as a result, it is more susceptible to nucleophilic attack. This means

condensation reactions occur preferentially between the neutral species and protonated

silanols that are located on monomers, end groups of chains, etc.

Pohl and Osterholtz proposed the following mechanism in acid-catalyzed

condensation reactions [72]:

R-Si(OH)3 H+ R-Si(OH)2

OH H+

R-Si(OH)2

OHH

+

+

+

fast

slowR-Si(OH)3 SiR

OH

OHO Si

OH

OH

R + H3O+

(1.42)

34

Based on this mechanism the condensation rate of reaction must be first-order in

protons and second-order in silanetriol (equation 1.43).

( )2

3R k RSi OH H +⎡ ⎤ ⎡ ⎤= ⎣ ⎦⎣ ⎦ (1.43)

The proposed reaction mechanisms for acid-catalyzed condensation involve

penta-coordinate or hexa-coordinate intermediates, the condensation reaction rate and

kinetics will be controlled by both steric and inductive factors. Replacement of more

electron-donating alkoxide (OR) groups with more electron-withdrawing hydroxyl (OH)

groups and (OSi) groups, stabilizes the negative charge on the anionic nucleophile that

is involved in the base-catalyzed condensation reaction and therefore can enhance the

rate of reaction. A similar explanation that extensive hydrolysis and condensation must

destabilize the positively charged intermediate or transition state in the acid-catalyzed

reaction may account for the reduced condensation reaction rate [66].

1.5.2.1.8 Base-Catalyzed Condensation

Pohel and Osterholtz [72] and Voronkov [73] propose mechanism for

deuteroxide (hydroxyl) anion and base-catalyzed condensation of alkylsilanetriol and

also alkylsilanediol:

(1.44)

Hydroxyl anion and silanetriol reversibly react rapidly in first step leading to an

equilibrium concentration of silanolate anion (RSi(OH)2O¯). Silanolate anion reacts

with neutral triol at a slower rate and produces dialkyl-tetra-hydroxydisiloxane and

regenerates hydroxyl anion. This reaction is first-order based on hydroxyl anion

(deuteroxide anion) and second-order in triol. The further condensation reaction of the

disiloxane is not a fast reaction due to steric effects.

35

Nano-silica structures can be altered by rate of hydrolysis and condensation

reactions. These rates of reactions can change with concentration of water, type and

concentration of catalyst (acid or base) and temperature [66].

1.6 Reinforced Networks

PEG-based networks have low mechanical properties, particularly compressive

strength, unless they are reinforced. This is an issue that has been resolved for many

crosslinked elastomers by the incorporation of particulate fillers and the same concepts

can be applied to networks.

According to Strachotova and colleagues the shear modulus in swollen (poly(N-

isopropylacrylamide) gels was improved up to 100 times with silica addition [74]. Loos

and co-workers verify that the modulus in hydrogels based on poly(N-vinylcaprolactam)

at equilibrium in water increases with rising amount of silica as reinforcement [75]. In

additon, Park and Cho show the interface between the reinforcement agent (silica with

different functional groups on the surface) and polymer bulk (styrene butadiene rubber)

can improve tearing energy from 55 kJ/m2 in neat silica to 62, 70 and 80 kJ/m2 in silica

with different surface chemistry (treatment with aminopropyl triethoxysilane (APS),

chloropropyl trimethoxysilane (CPS), and methacryloxypropyl trimethoxysilane

(MPS))[76].

1.6.1 Particulate Reinforced of low Modulus Materials

Most recently, the performance of polymeric materials has been enhanced by

nano-composites technology, in which the surface chemistry modification and the state

of dispersion of nano-particles such as exfoliated clays enhance tensile strength, thermal

stability and barrier properties compared to a macroscopic dispersion of clay particles

[77]. Polymeric nano-composites can be considered as organic-inorganic hybrid

materials in which inorganic nano-fillers (e.g., nano-particles, nano-tubes or nanometer-

thick sheets) are dispersed in an organic polymer matrix [78]. The composite materials

contain a third element that controls behavior of the composites. The third factor is the

interfacial interaction between fillers or inorganic nano-parts and polymer or organic

matrices [79, 80].

36

The improvement of properties strongly depends on the stress transfer between

the reinforcement particles and polymeric matrices [79, 81]. In well-bonded interface,

the applied tension can be effectively transferred from polymer to the reinforcement

agents, and can directly increase the strength and modulus of composites. However, in

poorly bonded micro-particles with polymer matrices, a decrease in strength can be

observed at higher loading [82].

In order to attain a better interaction between filler and polymer, the filler surface

can be modified by a coupling agent such as different types of organic silane [76, 79, 83,

84].

According to Huber and Vilgis [85], one of the reinforcing mechanisms in low

modulus polymer is hydrodynamic interactions. In this mechanism viscosity of liquid

part of viscoelastic material is enhanced by the addition of particles. Filler aggregation

and surface-polymer interaction on a small scale can change the intensity of mechanical

property enhancement. This binding can be chemical (covalent) or physical such as

hydrogen bonding between polymer chains and the particle surface.

In low modulus materials, particularly elastomers, the mechanical properties

depend on size, loading and shape of fillers. The other parameter is effect of level of

strain on the modulus. Above a certain level of deformation stress softening occurs and

modulus decreases which is known as the Mullins effect [86]. This is due to the

breakage of weak linkages between filler and polymer. The linkage in reinforced

polymer is formed with strong and weak linkages between network segments and filler

surface. The differences in linkage strength can cause molecular slippage in interface

which under stress surface-adsorbed segments move relative to the surface without

rupturing. The other mechanism is restricted mobility of the segments on the surface,

and an encapsulating shell around the particles is formed which increases the glass

transition temperature (Tg) in this layer. This phenomenon can be explained by dynamic

mechanical thermal analysis measurements [86].

According to Fu [82] toughness in polymeric composites that used silica

particles with surface chemical treatment compare to the same silica particles without

37

surface treatment were significantly improved. Interfacial debonding and delamination

controls the initiation and development of the failure process.

The other effect on polymer composite properties is the number of polymer

backbone conformations available in the presence of particles [84]. This effect can be

observed in the presence or even absence of particle-polymer interaction. In the

presence of a solid surface, the conformations of polymer backbones in the vicinity of

the particles are restricted and hindered. This restriction increases when polymer and

particles have better interaction.

Crystalline regions in semi-crystalline polymer can in turn affect the properties

of particulate composites. In addition, the crystallinity of polymer can be changed by

particles. Ultimately the crystalline region can alter the mechanical properties. The

mechanical properties of composites are modified by the level of crystallinity, crystal

types and phases, crystallite numbers, crystal orientation, shape and size of crystal. The

added particles in polymer bulk can act as nucleating agents. The nucleation process

causes rapid crystallization as well as alters the number and size of crystallites. In

polymeric composites Young’s modulus is one of the criteria for mechanical properties

improvement. Young’s modulus or the stiffness of a material is the ratio between stress

and strain at the elastic stage of tensile test. This value is improved when micro- and

nano-particles are added in a polymer matrix since the particles have greater stiffness

than the polymer matrix does [82].

1.6.2 Modification of the Surface of Silica

The surface modification of silica particles by silylation can improve adhesion

and compatibility between particles and polymer matrix [87]. For direct silica surface

reactions with any organo-silane, availability of silanol groups is necessary so the

majority of physisorbed water must be removed. Also this removal must be done in the

absence of condensation reaction of silanol groups.

In the presence of water, organo-silanes are hydrolyzed (equation 1.45 (a)) and

then condensation reaction either with another organo-silane (equation 1.45 (b)) or

silanol groups on the surface of silica (equation 1.45 (c)) can take place. Consequently,

all of the organo-silane groups cannot completely react with the surface of silica; also

38

small particles of silica with cage structures can be observed in the final products [52-

54, 87, 88]. The sol-gel method of silane reaction in presence of water can cause the

selective reaction of either self-condensation or grafting (equation 1.45). To avoid these

selective reactions, the silylation reaction must occur in completely dry conditions [87]

so that only reaction between organo-silane and silanol on the surface of silica can take

place [88].

CH2

CH2

Si

Si

Si

Si

SiSi

CH 2CH2

(1.45)

In this reaction, the number of available silanol groups on the surface plays a

key role. Surface area and structures such as number and size of pores are the other

parameters which can change the yield of surface reactions. Size and chemical structure

of the organic group of the organo-silane are other controlling parameters in yield of

functionalization reaction, because interaction of organic side of organo-silane with

silanol groups can change rate of reaction as well as rate of diffusion of silane side of

organo-silane (i.e. n-propyltriethoxysilane, 3-triethoxysilylpropylamine and

vinyltrimethoxysilane).

39

Si

SiSiSiSi

Si

(1.46) In equation 1.46 the full functionalization reaction has three steps. In each step,

one alkoxy arm of silane is reacted with silanol. The possibility of reaction in step (a)

and step (b) are higher compared to step (c) in which all three alkoxy groups are reacted

with the surface of a silica particle. This is because the availability of silanol on the

surface for the third alkoxy group can be very low. Also when nano-silica is used the

bonds in step (c) can be strained, so possibility of full reaction of silane with silica

surface can decrease. Although the reaction in step (c) can be very difficult, Greg and

his coworkers [89] mentioned step (c) of functionalization reaction can take place at

higher temperature and all three alkoxy groups can be chemically bonded to the surface

of silica. This is particularly so in porous as opposed to spherical silica where the

required geometry may be found inside the pores.

1.6.2.1 Silica structure

Depending on applications, silica is synthesized in different size, porosity and

surface structures. The physical properties of silica are highly influenced by surface

structure and the different functional groups binding to Si-O [90]. The most common

40

group that is chemically attached on the surface of silica is silanol group (Si-OH). There

are several types of silanol groups on the surface of silica include single isolated silanol

(Q3) (equation 1.47 (a)), geminal silanol (silanediol) (Q2) (equation 1.47 (b)), silanetriol

(Q1) (equation 1.47 (c)) and vicinal silanol (Q3) (equation 1.47 (d)). Thermal

dehydroxylation of surface of silica forms siloxane bridges (Q4) (equation 1.47 (e)) [55,

66, 91].

SiOH

OOSiOH

OOSiOH

OO OSiOH

OO O

Single isolatedSilanol

SiOH

OO O

Vicinal Silanol

SiOH

O

HO

O

Geminal Silanol

SiO

HOHO OH

Silanetriol

Si SiO

OSi

O

O

Siloxane Bridges

Si

Q1 Q2

Q3

Q4

Si Si

SiSi Si

Si Si Si Si SiSi

(1.47)

1.6.2.2 Hybrid Silica Structure

Silica, as discussed above, contains only silicon and oxygen in its structure

(SiO2) and also surface silanol groups (-Si-OH). As shown in equations 1.33, 1.34 and

1.35 these can be synthesized by hydrolysis and condensation reactions of tetra alkoxy

silanes such as TEOS. If an organo trialkoxy silane is used then an organo-

functionalized silica will result. For these types of silica surface structure, different types

of organo- silane can be used. Normal silane such as tetraethyl orthosilicate (TEOS) and

organo-silane such as (3-aminopropyl) triethoxysilane (APTES) are mixed for

synthesizing hybrid silica through sol-gel reaction. The other method is surface

treatment of a pre-formed silica particle with an organo-silane to make a hybrid silica

which will be discussed later. The mechanisim of synthesis has two steps, hydrolysis

and condensation.

41

Hybrid silica contains other structures, which are named T structures, in addition

to Q structures (which were shown in equation 1.47). When silicon links to a Carbon

atom through the organo-silane and links to one, two or three (O-Si) groups from

hydrolysis and condensation of the alkoxysilane, the silicone has T1, T2 or T3 structures

respectively (equation 1.48) [92]. All these species (Q and T structures) are detectable

by 29Si NMR.

(1.48)

1.7 Semicrystalline Polymer Properties and Structures in Networks

1.7.1 Crystal and Amorphous Regions in Semicrystalline Polymers

Polymer materials fall into two categories. The first group is amorphous

polymers in which polymer chains do not contain any crystalline regions. In the

amorphous polymer, chains are entangled with other polymer chains in a disordered way

and almost totally randomly. This entanglement improves amorphous polymer

properties as well as damping energy. Semicrystalline polymers contain both amorphous

and crystalline regions. The failure to achieve full crystallinity is a consequence of

polymer long chain nature which is caused by disorder in polymer chains and

42

subsequent entanglements [93]. Semicrystalline polymers above crystalline melting

point (Tm) transfer to a totally amorphous polymer.

1.7.1.1 Amorphous Polymer

Amorphous polymers physical and mechanical properties depend on temperature

and polymer chain structure. The glass transition temperature (Tg) is defined as the

temperature that polymer chains starts to perform rapid movement of the long-range

coordinated polymer backbone. This instantaneous movement above the glass transition

temperature (Tg) corresponds to a weak interaction between chains that allows

instantaneous conformation changes in polymers chains, however, the time for

observation of the movement must be relatively long compared to the time required for

these changes in conformations. In other words, the glass transition temperature (Tg)

value in a polymer sample highly depends on time, rate or frequency of measurement

[93]. The motion of a polymer in the amorphous state can take two forms. The first type

of motion is the chain changes in overall conformation, as in relaxation after strain. The

other type of motion is movement of a chain relative to its neighbor chains. Both of

these movements are considered as a type of self-diffusion.

1.7.1.2 Semicrystalline Polymer

Semicrystalline polymers are materials with highly ordered polymer chain

segment structures, remaining in the solid state until reaching the melting point. They

show a sharp melting point in the differential scanning calorimeter (DSC) and a given

quantity of heat is absorbed to rapidly change to the liquid state. Semicrystalline

polymers have both a glass transition temperature (Tg) and the melting or fusion

temperature (Tm or Tf) and the glass transition temperature is always lower than the

melting temperature [93].

The development of crystallinity in polymers is controlled by the regularity in

chain structure. Changes in tacticity can change the polymer’s degree of crystallinity.

The polymer with isotactic and syndiotactic sequences is usually crystallizable,

however, atactic irregularity in polymer chains can inhibit crystallization [93]. The

irregularity in polymer structure can decrease the melting temperature and ultimately the

crystallization process can be suppressed and prevented. The other factor is packing

43

ability of chains in the crystalline cells. This is related to chain flexibility such as in

PEG [93]. Crosslinked polymers can suppress crystallinity due to reduction of flexibility

and increase in irregularity. The polymer chain length is the other factor that can change

crystallinity as well as melting point. The chain length must be longer than the threshold

length to pack in crystal cells due to high mobility and chain end effects in the shorter

chains.

1.7.1.3 Kinetics of Crystallization

The rate of crystallization depends on several factors such as temperature,

molecular weight and polymer chain structure. The rate of crystallization at the melting

temperature is negligible. This rate increases as the temperature is decreased from the

melting point. The driving force for crystallization increases when temperature

decreases due to sample supercooling. However, the temperature drop has a promoting

effect on crystallization only until a certain temperature that shows the maximum rate of

crystallization, after which it dramatically decreases. This reduction is because the

polymer chain motion is hindered. Although the temperature can be above the glass

transition temperature (Tg), the motion of polymer chains is insufficient to be able to be

packed in the crystal cell and lamellae. The motion becomes sluggish when the

temperature gets closer to the glass transition temperature (Tg), that causes decrease in

the rate of crystallization effectively and ultimately approaches zero.

1.7.2 Thermal Fractionation of Semi-crystalline Polymers

Thermal fractionation technique is a practical method to evaluate chain

heterogeneities in semi-crystalline polymers. In thermal fractionation, recrystallization

occurs from melt. In other words, thermal fractionation is a temperature-dependent

segregation process. DSC is employed to perform thermal fractionation by different

methods such as self-nucleation and annealing (SSA) and step crystallization from the

melt (SC) [94, 95]. In these techniques polymer chains with side chains or with

irregularities pack in different crystalline structures and polymer chain segregation

occurs during this step crystallization process. Step crystallization from the melt (SC)

process depends on the stereo-regular segments and distribution of this regularity. In

other words, polymer segments crystallize at the specific temperatures (temperature

44

step). In SC method in each step polymer segments are subjected to isothermal

crystallization process and all chains which are able to be packed in this temperature

undergo packing process in crystalline regions with a lower number of defects on the

crystalline regions. These isothermal crystallization processes are repeated by stepping

to a lower temperature by cooling with rapid rate and holding at the new temperature for

a fixed time. The temperature step and time of isothermal process in each step depend

on chain structures and kinetics of crystallization. After the final step of the

crystallization process, the sample temperature is increased with a fixed ramping rate

and the resulting thermogram obtained [94].

1.8 Dynamic Mechanical Thermal Analysis (DMTA)

Polymer materials show viscoelastic behaviour ie. They have partial

characteristics of both viscous liquids and elastic solids. The elastic parts can store

mechanical energy without any energy dissipation, however, the viscous side of polymer

in a nanohydrostatic stress state illustrates energy dissipation without any storage of

energy. As a result, when a polymeric material is deformed under a certain amount of

load and any mode of deformation, a portion of the energy is stored as potential energy

and the rest of the input energy is dissipated as heat. The dissipated part of energy as

heat represents itself as mechanical damping energy or internal friction energy. This

internal friction energy is highly related to the type of polymer eg. an amorphous

viscoelastic polymer has rather high internal friction. Many mechanical properties are

intimately related to the internal friction energy, these include coefficient of friction,

wear and abrasion, breaking strain, impact strength and toughness and fatigue life [96].

The dynamic mechanical measurement is based on measuring the deformation of

polymer as a function of time in response to vibrational forces and stresses (sinusoidal

or other periodic stresses) [96, 97]. The dynamic modulus, the loss modulus and the

mechanical damping or internal friction can be obtained from this technique. This

measurement can be performed in a shear, tensile, compression or flexural modulus

mode of deformation over a wide range of temperatures and frequencies. The results of

the measurement are the glass transition temperature region, relaxation spectra, degree

of crystallinity, molecular orientation, crosslinking, phase separation, structural or

45

morphological changes due to processing and chemical composition in polymer blends

and copolymers [97].

DMTA also can show the relationships between the dynamic properties and

environmental or external variables such as temperature, pressure, mode of deformation,

humidity, active environment, time and frequency [96, 97]. The dynamic mechanical

thermal properties, especially the damping energy, are particularly sensitive to all kinds

of transitions, relaxation process, structural heterogeneities and the morphology of

multiphase systems [96].

Linear viscoelastic behavior can be explained by using several models eg.the

spring and dashpot model. When the spring and dashpot are in series it is a Maxwell

element model, and if they are parallel, it is a Voigt element model. Both of these

models are described by a relaxation or retention time which is shown as related to the

viscous damping constant:

Eητ = (1.49)

where η is the viscosity and E is the real modulus [97]. When a constant load is

subjected to the Maxwell element model, it shows instantaneous elastic deformation

which is followed by linear creep of the viscous element. If an instantaneous constant

strain is loaded, the stress-relaxation behavior in the Maxwell element model is an

instantaneous elastic response that decays exponentially. The Voigt element model

responds to a constant stress with asymptotically increasing strain. When the load is

removed, the deformation decays and the strain asymptotically approaches zero. The

combination of these elements produces a model that shows the combination of both

characteristics, i.e., instantaneous elastic, linear creep, and delayed elasticity. Analysis

of the behavior of this generalized model under a dynamic load has in turn led to a

concept of the complex modulus for characterization of the dynamic mechanical

properties of polymers. For example stress-strain relationship for the generalized

Maxwell model with infinite number of basic elements (spring and dashpot) which are

deformed with a periodic input (ε = ε0 exp (iωt)) with constant angular frequency (ω)

can be shown:

46

( ) 0' " i tE iE e ωσ ε= + (1.50)

where E’ is the young storage modulus, E” is the loss modulus, ε0 is the

maximum value of the strain amplitude during a cycle, t is the time and i is equal to

1− . As a result the complex modulus (E*) is shown:

* ' "E E Eσε

∂= = +

∂ (1.50)

in this equation E’ and E” are functions of continuous distribution of relaxation times

( ( )φ τ ):

( )2 2

2 20

'1

E dω τ φ τ τω τ

∞

=+∫ (1. 51)

and

( )2 20

"1

E dωτ φ τ τω τ

∞

=+∫ (1. 52)

Based on the generalized Maxwell element model the complex formulation

shows the stress is out of phase with the applied strain.

By regarding equation 1.50 it can be changed to an elastic modulus and viscous

damping constant in terms of the Voigt element model in a viscoelastic polymer at a

given frequency:

' dEdtεσ ε η= + (1. 53)

where "Eη ω= and it shows the elastic behavior (real part) is the non time-dependent

component and the complex component which gives the dissipative properties is a time-

dependent component. However both the real part and complex component are a

function of frequency [97].

The ratio between E” and E’ which is called damping is known as tan δ

(equation 1.54), where δ is phase angle (the angle differences between E” and E’).

"tan'

EE

δ = (1.54)

47

tan δ is used to measure all relaxation processes in dynamic mechanical analysis.

1.8.1 Temperature Dependent Properties in Dynamic Mechanical Thermal

Analysis

1.8.1.1 Glass Transition Temperature

The thermal properties such as heat capacity and thermal expansion coefficient

undergo abrupt changes in the glass transition temperature region. Most amorphous

polymers are hard and rigid glasses below the glass transition temperature. In other

words, the polymer chain segments are frozen and fixed in their position and only have

weak vibrational motion. Close to the glass transition temperature, motion and

movement of the polymer chains can be initiated with temperature increases. In this

stage the thermal energy becomes comparable to the potential energy barriers to

segmental rotation movement. The polymer segments can move from one lattice to

another, this is the reason the rigid polymer becomes soft and rubbery. In other words,

many mechanical properties change around the glass transition temperature due to onset

of chain movement. As an example, the dynamic modulus (storage modulus) decreases

rapidly (Figure 1. 5), the loss modulus shows a maximum value and the tan δ exhibits a

maximum. The loss modulus and the tan δ show maxima curves, however, the

maximum in the loss modulus appears at lower temperature compared to the maximum

value in tan δ. These changes are so strong that the dynamic mechanical thermal

analysis technique can readily measure the glass transition temperature as well as any

change in this temperature, for both blends and composites.

It is necessary to note that because of the frequency dependence of DMTA the

glass transition temperature may differ from that run at a different frequency as well as

by a different experiment such as DSC. Polymeric materials do not have a fixed glass

transition temperature. This temperature can be shifted under the influence of flexibility

of the chains, steric hindrance, size and nature of the side groups attached to the

backbone, symmetry in the structure, crosslinking, molecular weight, degree of

crystallinity, plasticizers, fillers and impurities [24, 96, 97]. As a result, the glass

transition temperature can be affected by changes in the crystalline region. This is

48

because cohesive energy and molecular packing affect both the amorphous and

crystalline region. The reflection of these interactions can be observed in shifts in all

transition temperatures [96, 97].

Figure 1. 5. Modulus change versus temperature from below Tg to flow

temperature. Modes of energy dissipation with each relaxation are shown (taken

with permission from Chemorheology of Polymers: From Fundamental Principles to

Reactive Processing [24]).

The loss modulus (E”) shows a peak which has a maximum that is slightly

shifted to lower temperature compared to the internal friction (tan δ). At the temperature

that E” is maximum the highest heat dissipation per unit of deformation can be observed

[97].

Other relaxation transitions can be observed in the glassy state which is below

the glass transition temperature on the lower-temperature side of the primary dispersion.

These relaxation transitions are named as secondary dispersions that are called β- and γ-

transitions, in order of decreasing temperature [97]. The β-transition is associated with

49

crankshaft motion [24] and the γ-transition involves motion of the small groups attached

to the main chain (Figure 1. 5).

In semi-crystalline polymers, the α-transition peak is shifted to higher

temperature compared to totally amorphous or less crystalline versions of the same

polymer due to the motion in neighboring polymer chains in the crystalline region being

hindered.

In highly crystalline polymers, another transition between the α-transition and

melting temperatures can be observed which is the highest relaxation temperature [97-

99]. This relaxation which is named as αc or α’-relaxation is associated with molecular

motion in the crystalline phase. Takayanagi (cited by Murayama [97]) mentioned that

this crystalline transition is because of the frictional viscosity between specific

crystalline planes or molecules inside the crystals. The α’-transition depends on the

crystallite thickness and the method of crystallization and recrystallization [100]. The

α’-transition will be discussed in detail below as it is important in PEG relaxation

processes.

1.8.1.2 The α’-Transition in Semi-crystalline Polymers

As noted above, in semi-crystalline polymers at least one extra relaxation peak

can be seen in between the melting temperature and the glass transition temperature

which is attributed to polymer chains in or neighboring the crystalline phase [99]. The

amplitude of this peak increases when the crystalline fraction increases. This relaxation

is caused by the flip-flop mechanism and/or the screw motion of methylene groups in

the crystal lattice. The distortion of the C-C skeleton can propagate through the crystal

lattice and in doing so causes transport of the distortion and hence diffusion [98, 99,

101]. This transition is related to rotation of the chain axis of chain-folded polymers

(defects) [97, 102], and in particular, Mansfield shows the rotation is a 180° twist at

defects [102] which propagates along the chain and across the crystal [99]. Boyd

explained the rotation as a 180° screw rotation which advances the chain by half a unit

cell (c/2) and this rotation is developed by a twist which moves through the crystal

(Figure 1. 6) [101]. The motion of a twist is started at one surface of the crystal, then by

hopping over the local barrier at each CH2 site (diffusive passage) moves along the

50

oriented chain. In the Mansfield and Boyd model [98, 102]) the chain has a twisted

region which is limited (~ 12 CH2 in poly olefin (PE) or several repeating units CH 2-

CH 2-O in PEG) and relatively uniform with each bond angle being distorted. This

smooth twist fits into the crystalline lattice due to lower defect energy (Figure 1. 6). This

means there is no local hopping in the motion across the crystal [101]. The Mansfield

and Boyd theory says that the α’-transition temperature depends on the crystalline layer

thickness. The α’-transition is related to segmental motion in crystallites prior to

melting.

Figure 1. 6. Origin of the α’-transition: Propagation of localized smooth twist along

the chain. At the starting point of the twist (1) it leaves a transitional mismatch.

When the twist continues (2) the mismatch becomes attenuated at large distances

from the twist (Adapted from [101]).

In the α’-transition region the mobility of the chains in the crystalline region has

been observed by NMR. Tagayanagi (cited by Rault [99]) observed the α’-transition by

DMTA which was not due to premelting effects but to chain mobility in the crystals.

However, in some stiffer semi-crystalline polymer the α’-transition and premelting are

believed to occur at the same temperature [99].

The α’-transition is defined as the temperature at the maximum of tan δ, as a

result, it is frequency dependent. This temperature is readily detectable in polyolefins

and polyethers which have the α’-transition temperature far below the melting point. In

polymers with bulky groups or with strong hydrogen bonding, the α’-transition gets very

close to the melting point temperature, and the melting transition is large, so detection of

the α’-transition peak can be difficult. Rault [99] shows the rapid increase in creep in

51

semi-crystalline polymers begins to be operative at the α’-transition temperature. This is

because at the α’-transition temperature chains in the crystalline have sufficient mobility

to participate in the creep process. This involves chains either being pulled out of the

crystallites or they are able to glide in the crystal lattice.

1.9 Conclusion

This review has been highly selective and has covered a wide field without great

depth to any one area. After an introduction to the process of scar formation and

remediation, the theory of gels, reinforced polymers, silica surface treatment and

methods for incorporating organic linker groups have been introduced. The principles of

sol-gel chemistry have been discussed in more detail in order to provide a basis for the

methodology that is used in the next chapter to produce the target materials. The basics

of polymer relaxations and measurement by dynamic mechanical thermal analysis have

been introduced as this is a major characterization tool that is used for the PEG networks

made by the sol-gel process. Only an outline has been given of the process of

reinforcement of networks with silica, both added directly and in situ, but this will be

elaborated further when specific networks are discussed.

References:

1. Joseph, E., Hamori, C. A., Bergman, S., Roaf, E., Swann, N. F. and Anastasi, G.

W., A Prospective, Randomized Trial of Vacuum-assisted Closure Versus Standard Therapy of Chronic Non-healing Wounds. Wounds, 2000. 12: p. 60-67.

2. Coté, M., Albert, M., Attrell, E. and Beaumier, M., Acute Wounds. Wound Care Canada, 2008. 6(2): p. 20-22.

3. Church, D., Elsayed, S., Reid, O., Winston, B. and Lindsay, R., Burn Wound Infections. Clin. Microbiol. Rev., 2006. 19(2): p. 403-434.

4. Aarabi, S., Longaker, MT. and Gurtner, GC., Hypertrophic Scar Formation Following Burns and Trauma: New Approaches to Treatment. PLoS Med., 2007. 4(9): p. 1464-1470.

5. Sanchez, W., Evans, J. and George, G., Silicone Polymers in Scar Remediation: The Role of Migration of Oligomers Through Stratum Corneum. Aust. J. Chem, 2005. 58: p. 447-450.

6. Tsao, S., Dover, JS., Arndt, KA. and Kaminer, MS., Scar Management: Keloid, Hypertrophic, Atrophic, and Acne Scars. Seminars in Cutaneous Medicine and Surgery, 2002. 21(1): p. 46-75.

52

7. Bloemen, M.C.T., Van der Veer, WM., Ulrich, MW., Van Zuijlen, PM., Niessen, FB. and Middelkoop E., Prevention and Curative Management of Hypertrophic Scar Formation. Burns, 2008. 35(4): p. 463-475.

8. Occleston, N.L., O'Kane, S., Goldspink, N. and Ferguson, M. W., New Therapeutics for the Prevention and Reduction of Scarring. Drug Discovery Today, 2008. 13(21/22): p. 973-981.

9. Buder, P., Longaker, MT. and Yang, GP., Current Progress in Keloid Research and Treatment. J. Am. Coll. Surg., 2008. 206(4): p. 731-741.

10. Robles, D.T., Berg, D., Abnormal Wound Healing: Keloids. clinics in Dermatology, 2007. 25: p. 26-32.

11. Urioste, S., Arndt, KA. and Dover, JS., Keloids and Hypertrophic Scars: Review and Treatment Strategies. Seminars in Cutaneous Medicine and Surgery, 1999. 18(2): p. 159-171.

12. Danielson, J.R., Walter, R. J., Case Studies: Use of Salicylic Acid (Avosil®) and Hydrogel (Avogel®) in Limiting Scar Formation. Journal of Burns and Wounds, 2005. 4(6): p. 119-127.

13. Momeni, M., Hafezi, F., Rahbar, H. and Karimi, H., Effects of Silicone Gel on Burn Scars. Burns, 2009. 35(1): p. 70-74.

14. Li-Tsang, C.W., Lau, J. C., Choi, J., Chan, C. C. and Jianan, L., A Prospective Randomized Clinical Trial to Investigate the Effect of Silicone Gel Sheeting (Cica-Care) on Post-Traumatic Hypertrophic Scar Among the Chinese Population. Burns, 2006. 32: p. 678–683.

15. Sawada, Y., Sone, K., Treatment of scars and keloids with a cream containing silicone oil. Br J Plas Surg, 1990. 43: p. 682-688.

16. Van den Kerckhove, E., Stappaerts, K., Boeckx, W., Van den Hof, B., Monstrey, S., Van der Kelen, A. and De Cubber, J., Silicones in the rehabilitation of burns: a review and overview. Burns, 2001. 27: p. 205-214.

17. Suetake, T., Sasai, S., Zhen,YX. and Tagami, H., Effects of Silicone Gel Sheet on the Stratum Corneum Hydration. British Journal of Plastic Surgery, 2000. 53: p. 503-507.

18. Wichterle, O., Lím, D., Hydrophilic Gels for Biological Use. NATURE, 1960. 185: p. 117-118.

19. Lin, C., Metters, AT., Hydrogels in Controlled Release Formulations: Network Design and Mathematical Modeling. Adv. Drug Delivery Rev., 2006. 58: p. 1379-1408.

20. Hoffman, A.S., Hydrogels for Biomedical Applications. Adv. Drug Delivery Rev., 2002. 43: p. 3–12.

21. Kopecek, J., Swell Gels. Nature, 2002. 417: p. 388-391. 22. Hennink, W., van Nostrum, CF., Novel crosslinking methods to design

hydrogels. Adv. Drug Delivery Rev., 2002. 54: p. 13-36. 23. Lowman, A., Peppas, NA., Encyclopedia of Controlled Drug Delivery, in

Hydrogels, E. Mathiowitz, Editor. 1999, Wiley-Interscience: New York. p. 397-418.

24. Halley, P.J., George, G. A., Chemorheology of Polymers: From Fundamental Principles to Reactive Processing. 2009, New York: Cambridge University Press.

53

25. Serra, L., Doménech, J. and Peppas, N. A., Engineering Design and Molecular Dynamics of Mucoadhesive Drug Delivery Systems as Targeting Agents. Eur. J. Pharm. Biopharm., 2008. 71(3): p. 519-528.

26. Spizzirri, U.G., Peppas, N., A., Structural Analysis and Diffusional Behavior of Molecularly Imprinted Polymer Networks for Cholesterol Recognition. Chem. Mater., 2005. 17: p. 6719-6727.

27. Amsden, B., Solute Diffusion within Hydrogels. Mechanisms and Models. Macromolecules, 1998. 31: p. 8382-8395.

28. Siepmann, J., Siepmann, F., Mathematical Modeling of Drug Delivery. Int. J. Pharm., 2008. 364: p. 328–343.

29. Siepmann, J., Peppas, N., Modeling of Drug Release from Delivery Systems Based on Hydroxypropyl Methylcellulose (HPMC). Adv. Drug Delivery Rev., 2001. 48: p. 139–157.

30. Cohen, D., Erneux, T., Free Boundary Problems in Controlled Release Pharmaceuticals. II: Swelling-Controlled Release. SIAM J. Appl. Math., 1988. 48: p. 1466-1474.

31. Dhanpal, P., Yiy, CKY., King, NM., Tay, FR. and Hiraishi, N., Effect of Temperature on Water Sorption and Solubility of Dental Adhesive Resins. Journal of Dentistry, 2009. 37: p. 122-132.

32. Namazi, H., Kanani, A., Investigation Diffusion Mechanism of β-lactam Conjugated Telechelic Polymers of PEG and β-Cyclodextrin as the New Nanosized Drug Carrier Devices. Carbohydrate Polymers, 2009. 76(1): p. 46-50.

33. Suzuki, Y., Tomonaga, K., Kumazaki, M. and Nishio, I., Change in phase transition behavior of an NIPA gel induced by solvent composition: hydrophobic effect. Polvmer Gel and Networks, 1996. 4: p. 129-142.

34. Shenoy, S.L., The Effect of Uniaxial Deformation on Swollen Gels. Polym. Gels Networks, 1998. 6: p. 455-470.

35. Kayman, N., Okay, O. and Baysal, B. M., Swelling of Polyacrylamide Gels in Polyacrylamide Solutions. j. Polym. Sci. Polym. Phys., 1998. 36: p. 1313-1320.

36. Melekaslan, D., Okay, O., Reentrant Phase Transition of Strong Polyelectrolyte Poly(N-isopropylacrylamide) Gels in PEG Solutions. Macromol. Chem. Phys., 2001. 202: p. 304-312.

37. Melekaslan, D., Okay, O., Swelling of Strong Polyelectrolyte Hydrogels in Polymer Solutions: Effect of Ion Pair Formation on the Polymer Collapse. Polymer, 2000. 41: p. 5737-5747.

38. Okay, O., Gundogan, N., Volume Phase Transition of Polymer Networks in Polymeric Solvents. Macromol. Theory Simul., 2002. 11(3): p. 287-292.

39. Milton, H.J., Poly(ethylene glycol) Chemistry : Biotechnical and Biomedical Applications. 1992, New York: Humana Press Inc.

40. Rocks, J., Rintoul, L., Vohwinkel, F. and George. G., The kinetics and mechanism of cure of an amino-glycidyl epoxy resin by a co-anhydride as studied by FT-Raman spectroscopy. Polymer, 2004. 45: p. 6799–6811.

41. Laine, R.M., Kim, S. G., Rush, J., Mollan, M., Sun, H. J. and Lodaya, M., Ring-opening Polymerization of Epoxy End-terminated Poly(ethylene oxide) as a Route to Highly Crosslinked Materials with Exceptional Swelling Behavior (II). Polym. Int., 2007. 56: p. 1006–1015.

54

42. Laine, R.M., Kim, S. G., Rush, J., Tamaki, R., Wong, E., Mollan, M., Sun, H. J. and Lodaya, M., Ring-Opening Polymerization of Epoxy End-Terminated Polyethylene Oxide (PEO) as a Route to Cross-Linked Materials with Exceptional Swelling Behavior. Macromolecules, 2004. 37(12): p. 4525-4532.

43. Nakajima, N., Ikada, Y., Mechanism of Amide Formation by Carbodiimide for Bioconjugation in Aqueous Media. Bioconjugate Chem., 1995. 6(1): p. 123-130.

44. Hou, S., McCauley, L. K. and Ma, P. X., Synthesis and Erosion Properties of PEG-Containing Polyanhydrides. Macromol. Biosci., 2007. 7: p. 620-628.

45. Moore, J.S., Stupp, S. I., Room Temperature Polyesterification. Macromolecules, 1990. 23(1): p. 65-70.

46. Daniel-da-Silva, A.L., Bordado, J. C. M. and Martýń-Martýńez, J. M., Moisture Curing Kinetics of Isocyanate Ended Urethane Quasi-Prepolymers Monitored by IR Spectroscopy and DSC. J. Appl. Polym. Sci., 2008. 107: p. 700-709.

47. Mehdipour-Ataei, S., Keshavarz, S., Synthesis and Characterization of Novel Diimide–Dinaphthols and Resulting Poly(Urethane–imide)s. Polym. Int., 2003. 52: p. 1487–1492.

48. Van Maris, R., Tamano, Y., Yoshimura, H. and Gay K. M., Polyurethane catalysis by tertiary amines. Journal of Cellular Plastics, 2005. 41(4): p. 305-322.

49. Houghton, R.P., Mulvaney, A. W., Mechanism of Tint IV) -Catalysed Urethane Formation. J. Organomet. Chem., 1996. 518: p. 21-27.

50. Cruise, G.M., Hegre, O. D., Scharp, D. S. and Hubbell, J. A., A Sensitivity Study of the Key Parameters in the Interfacial Photopolymerization of Poly(ethylene glycol) Diacrylate upon Porcine Islets. Biotechnol. Bioeng., 1998. 57(6): p. 655-665.

51. Guo, K., Chu, C. C., Synthesis and Characterization of Novel Biodegradable Unsaturated Poly(ester amide)/Poly(ethylene glycol) Diacrylate Hydrogels. J. Polym. Sci., Part A: Polym. Chem., 2005. 43: p. 3932–3944.

52. Luechinger, M., Prins, R. and irngruber, D. G., Functionalization of Silica Surfaces with Mixtures of 3-aminopropyl and Methyl Groups. Microporous Mesoporous Mater., 2005. 85: p. 111-118.

53. Chen, W., Feng, H., He, D. and Ye, C., High Resolution Solid-State NMR and DSC Study of Poly (ethylene glycol )-Silicate Hybrid Materials Via Sol–Gel Process. J. Appl. Polym. Sci., 1998. 67: p. 139-147.

54. Tripp, C.P., Hair, M. L., Reaction of Methylsilanols with Hydrated Silica Surfaces: The Hydrolysis of Trichloro-, Dichloro-, and Monochloromethylsilanes and the Effects of Curing. Langmuir, 1995. 11: p. 149-155.

55. Barbe´, C., Bartlett, J., Kong, L., Finnie, K., Lin, H. Q., Larkin, M., Calleja, S., Bush, A. and Calleja, G., Silica Particles: A Novel Drug-Delivery System. Adv. Mater., 2004. 16: p. 1959-1966.

56. Salamone, J.C., Concise Polymeric Materials Encyclopedia. 1999, New York: CRC.

57. Odian, G., Principales of Polymerization. Fourth ed. 2004, Hoboken: John Wiley & Sons, Inc.

55

58. Flory, P.J., Principles of Polymer Chemistry. sixteenth ed. 1995, New York: Cornell University Press.

59. Chujo, Y., Saegusa, T., Organic Polymer Hybride with Silica Gel Formed by Means of the Sol-Gel Method. Adv. Polym. Sci., 1992. 100: p. 11-29.

60. Ogoshi, T., Chujo, Y., Synthesis of colloidal polyoxazoline/silica hybrids prepared in an aqueous solution. Polymer, 2006. 47: p. 4036-4041.

61. Oh, C., Ki, C. D., Chang, J. Y. and Oh, S. G., Preparation of PEG-grafted Silica Particles Using Emulsion Method. Mater. Lett., 2005. 59: p. 929–933.

62. Granqvist. B., H., A., Vehvilainen, M., Aaritalo, V., Seppala, J. and Linden, M., Biodegradable and bioactive hybrid organic–inorganic PEG-siloxane fibers. Preparation and characterization. colloid. Polym. Sci., 2004. 282: p. 495-501.

63. Kweon, J., Noh, S., Thermal, Thermomechanical, and Electrochemical Characterization of the Organic–Inorganic Hybrids Poly(ethylene oxide ) (PEO)–Silica and PEO–Silica–LiClO4. J. Appl. Polym. Sci., 2001. 81: p. 2471-2479.

64. Kweon, J., Noh, S., Thermal and Thermomechanical Properties of Poly(ethylene oxide) Networks Produced with Silica and Organic Crosslinking Agents. J. Appl. Polym. Sci., 2003. 90: p. 270-277.

65. Iler, R.K., The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties,and Biochemistry. 1979, New York: John Wiley and Sons.

66. Brinker, C.J., Scherer, G. W., Sol-gel Science, the Physics and Chemistry of Sol-gel Processing. 1989, San Diego: Academic Press.

67. Aelion, R., Loebel, A. and Eirich, F., Hydrolysis of Ethyl Silicate. J. Am. Chem. Soc., 1950. 72: p. 5705-5712.

68. McNeill, K.J., DiCaprio, J. A., Walsh, D. A. and Pratt, R. F., Kinetics and Mechanism of Hydrolysis of a Silicate Triester, Tris( 2-methoxyethoxy )phen ylsilane. J. Am. Chem. Soc., 1980. 102(6): p. 1859-1865.

69. Deiters, J.A., Holmes, R., Pathways for Nucleophilic Substitution at Silicon. A Molecular Orbital Approach. J. Am. Chem. Soc., 1987. 109: p. 1686-1692.

70. Deiters, J.A., Holmes, R., Effect of Entering and Leaving Groups on Nucleophilic Substitution Reactions at Silicon. A Molecular Orbital Approach. J. Am. Chem. Soc., 1987. 109: p. 1692-1692.

71. Corriu, R.J., Guerin, C., Nucleophilic Displacement at Silicon Stereochemistry and Mechanistic Implications. J. Organomet. Chem., 1980. 198: p. 231-320.

72. Pohl, E.R., Osterholtz, F. D., Molecular Characterization of Composite Interfaces, ed. H. Ishida, Kumar, G. 1985, New York.

73. Voronkov, M.G., Mileshkevich, V. P. and Yuzhelevski, Y. A., The Siloxane Bond. 1978, New York: Consultants Bureau.

74. Strachotová, B., Strachota, A., Uchman, M., Slouf, M., Brus, J., Plestil, J. and Matejka, L., Super Porous Organic-Inorganic Poly(N-isopropylacrylamide)-based Hydrogel with a very Fast Temperature Response. Polymer, 2007. 48(6): p. 1471-1482.

75. Loos, W., Verbrugghe, S., Goethals, E. J., Du Prez, F. E., Bakeeva, I. V. and Zubov, V., Thermo-Responsive Organic/Inorganic Hybrid Hydrogels based on Poly(N-vinylcaprolactam). Macromol. Chem. Phys., 2003. 204(1): p. 98-103.

56

76. Park, S., Cho, K., Filler-Elastomer Interactions: Influence of Silane Coupling Agent on Crosslink Density and Thermal Stability of Silica/Rubber Composites. J. Colloid Interface Sci., 2003. 267(1): p. 86-91.

77. Poovarodom, S., Hosseinpour, D. and Berg, J. C., Effect of Particle Aggregation on the Mechanical Properties of a Reinforced Organic-Inorganic Hybrid Sol-Gel Composite. Ind. Eng. Chem. Res., 2008. 47(8): p. 2623-2629.

78. Friedrich, K., Fakirov, S. and Zhang, Z., Polymer Composites From Nano- to Macro- Scale. 2005, New York: (Springer Science+Business Media, Inc.

79. Gojny, F.H., Wichmann, M. H. G., Fiedler, B. and Schulte, K., Influence of Different Carbon Nanotubes on the Mechanical Properties of Epoxy Matrix Composites – A Comparative Study. Compos. Sci. Technol., 2005. 65: p. 2300–2313.

80. Liu, Y.J., Nishimura, N., Otani, Y. and Mokashi, V., A Boundary Element Method for the Analysis of CNT/Polymer Composites with a Cohesive Interface Model Based on Molecular Dynamics. Eng. Anal. Boundary Elem., 2008. 32: p. 299–308.

81. Lauke, B., On the Effect of Particle Size on Fracture Toughness of Polymer Composites. Compos. Sci. Technol., 2008. 68: p. 3365–3372.

82. Fu, S.Y., Feng, X. Q., Lauke, B. and Mai, Y. W., Effects of Particle Size, Particle/matrix Interface Adhesion and Particle Loading on Mechanical Properties of Particulate–polymer Composites. Composites: Part B, 2008. 39: p. 933-961.

83. Sheldon, R.P., Composite Polymeric Materials. 1982, London: Applied Science Publishers.

84. Rothon, R., Particulate-Filled Polymer Composites. 1995, New York: John Wiley & Sons Inc.

85. Huber, G., Vilgis, T., On the Mechanism of Hydrodynamic Reinforcement in Elastic Composites. Macromolecules, 2002. 35: p. 9204-9210.

86. Paipetis, S.A., Interfacial Phenomena and Reinforcing Mechanisms in Rubber/Carbon Black Composites. Fibre Sci. Technol., 1984. 21(2): p. 107-124.

87. Lin, J., Siddiqui, J. A. and Ottenbrite, R. M., Surface Modification of Inorganic Oxide Particles with Silane Coupling agent and Organic dyes. Polym. Adv. Technol., 2001. 12: p. 285-292.

88. Pham, K.N., Fullston, D. and Sagoe-Crentsil, K., Surface Modification for Stability of Nano-Sized Silica Colloids. J. Colloid and Interface Sci., 2007. 315: p. 123–127.

89. Garg, B., S., Bist, J. S., Sharma, R. K. and Bhojak, N., Solid-phase Extraction of Metal ions and Their Estimation in Vitamins, Steel and Milk Using 3-hydroxy-2-methyl- 1,4-naphthoquinone-immobilized Silica Gel. Talanta, 1996. 43: p. 2093-2099.

90. Senn, B.C., Pigram, P. J. and Liesegang, J., Surface Electrical Resistivity and Wettability Study of Fused Silica. Surf. Interface Anal., 1999. 27: p. 835–839.

91. Barbe´, C.J., Kong, L., Finnie, K. S., Calleja, S., Hanna, J. V., Drabarek, E., Cassidy, D. T. and Blackford, M. G., Sol–gel Matrices for Controlled Release: From Macro to Nano Using Emulsion Polymerisation. J Sol-Gel Sci. Technol., 2008. 46: p. 393–409.

57

92. Singh, R.P., Way, J. D. and Dec, S. F., Silane Modified Inorganic Membranes: Effects of Silane Surface Structure. J. Membr. Sci., 2005. 259: p. 34–46.

93. Sperling, L.H., Introduction to Phsycal Polymer Science. 4th ed. 2006, New Jersey: John Wiley & Sons, Inc.

94. Muller, A.J., Arnal, M. L., Thermal fractionation of polymers. Prog. Polym. Sci., 2005. 30: p. 559-603.

95. Keating, M., Lee, I. and Wong, C. S., Thermal Fractionation of Ethylene Polymers in Packaging Applications. Thermochim. Acta, 1996. 284: p. 47-56.

96. Nielsen, L.E., Landel, R. F., Mechanical Properties of Polymers and Comopsites. 2nd ed. 1994, New York: Marcel dekker, Inc.

97. Murayama, T., Dynamic Mechanical Analysis of Polymeric Material. Vol. 1. 1978, Amsterdam: Elsevier Scientific Publishing Company.

98. Mansfield, M., Boyd, R. H., Molecular Motions, the α Relaxation, and Chain Transport in Polyethylene Crystals. J. polym. Sci. Polym. Phys. Ed., 1978. 16: p. 1227-1252.

99. Rault, J., The αC Transition in Semicrystalline Polymers: A New Look at Crystallization Deformation and Aging Process. Polym. Rev., 1997. 37(2): p. 335-387.

100. Simon, L.C., De Souza, R. F., Soares, J. B. P. and Mauler, R. S., Effect of Molecular Structure on Dynamic Mechanical Properties of Polyethylene Obtained with Nickel–diimine Catalysts. polymer, 2001. 42: p. 4885-4892.

101. Boyd, R.H., Relaxation Processes in Crystalline Polymers: Molecular Interpretation - a Review. Polymer, 1985. 26: p. 1123-1133.

102. Skinner, J.L., Park, Y. H., Soliton Model for Dielectric Relaxation in Crystalline Polyethylene. Comparison with Experiment. Macromolecules, 1984. 17(9): p. 1735-1740.

58

Chapter 2: Experimental Methodology

2.1 Functionalization of Silica Surface

The crosslinking reactions to form the PEG gels for delivery of the amphiphilic

silicone oligomers involve silica as the crosslinking site and sol-gel chemistry is one

approach that has been researched to achieve active silica (chapter one, section 1.5.2).

Neat silica has silanol groups on the surface. For changing and modifying the surface of

silica these silanol groups can be used as active sites (chapter one, section 1.6.2). For

functionalization reactions, organo-silanes are employed.

2.1.1 Silica Surface Modification Procedure

The calculated amount (2 g) of hydrophilic silica AEROSIL® 300 with 4 silanol

(-Si-OH) groups per 1 nm2 was weighed in a two-neck round bottom flask and a Teflon

magnetic stirring bar was placed in the flask. In order to remove physisorbed water on

the surface of hydrophilic silica, a vacuum oven was used (as mentioned in chapter one

section 1.6.2, silica surface needs to be dried). The temperature must be held between

115 to 120 °C under full vacuum condition for at least 24 hours. During this drying

process, the oven had to be purged with ultra high purity argon to remove all

physisorbed water. The flask was moved from the oven when the temperature reached

room temperature under argon to prevent any water adsorption. Around 50 ml dried

toluene (dried over sodium strips) or dried dichloromethane (DCM) was added to the

flask under an argon stream. Then it was heated at 50 °C (DCM had to be heated at 40

to 45 °C) in the oil bath and stirred. Organo-silane chemicals were added by two

different methods which depended on the type of organo-silane:

• For triethoxyvinylsilane and trimethoxypropylsilane, 2 ml of silane was added

directly into the flask under argon flow. Several drops of triethylamine as a catalyst

were added to the flask. The suspension was stirred under argon at 50 °C (toluene as a

solvent) in the oil bath under argon overnight [1].

• In the synthesized organo-silane with a long organic tail such as

triethoxyPEO2000silane, firstly, 10 g silane was dissolved in dried DCM. The silane

59

solution was poured in a pressurized dropping funnel under argon to prevent hydrolysis

of any alkoxy group. In the first method all of the triethoxyPEO2000silane solution was

added into the silica suspension (this is named DCM1). In the second method the silane

solution was gradually added to the flask which contained dried suspended silica with

several drops of triethylamine as a catalyst over three hours at 40 to 45 °C. The

suspension was stirred under a positive pressure of ultra high purity argon (this is named

DCM2).

All solvent and unreacted chemicals were removed by the rotary evaporator at 40

to 45°C under vacuum. The products were further dried in the vacuum oven at 60 to 70

°C and then left in this condition for 48 hours in order to complete the reaction between

the alkoxy groups in silane and silanol groups on the surface of silica. The dried

products were removed to a soxhlet extraction thimble and purified by extraction with

tetrahydrofuran (THF) for at least 6 hours. The products were placed in the vacuum

oven at 40 °C overnight [1]. The products were analyzed and characterized by TGA and 29Si Solid State NMR.

2.2 Synthesis of Silane-Terminated Polyethylene glycol (PEG)

2.2.1 Bis(trialkoxy silyl)-PEG Synthesis Procedure Bis(trialkoxy silyl)-PEG was synthesized by three different methods with three

types of organo-silanes:

1. The first method used reaction between hydroxyl groups on both ends of PEG

and (3-Glycidyloxypropyl)trimethoxysilane (GPS). 0.0025 mol PEG (5g of PEG 2000

Da and 25g of PEG 10000 Da) was weighed into a two necked round bottom flask and

dried on the high vacuum line at 95 to 100 °C in the oil bath and stirred for at least three

hours. After drying, the flask was sealed under ultra high purity argon to pressurize the

contents in an inert atmosphere and the flask was then moved into the dry box for

adding sodium hydride (NaH) under absolutely dry conditions (chapter one, equation

1.11). The amount of sodium hydride was 10% excess molar ratio (0.132 g). The flask

was moved out of the dry box after sealing. Polyethylene glycol (PEG) was reacted with

sodium hydride and formed dianion PEG in two ways, by molten and solution reactions

[2]:

60

(a) In the molten polymer reaction, PEG and NaH were mixed under vacuum at 95

°C which was above the melting point temperature of PEG. The hydrogen gas was

removed from the vessel under vacuum. Molten PEG and sodium hydride had to be

mixed thoroughly to ensure homogeneous reaction.

(b) In the solution method, PEG and NaH were dissolved in dried tetrahydrofuran

(THF) (50ml in PEG2000 and 250ml in PEG 10000) that was previously dried over

potassium and kept under argon positive pressure. The solvent had to be carefully dried

to prevent any sodium hydroxide formation. The solution was stirred at 50 °C until all

PEG dissolved and then cooled and stirred for four hours at room temperature.

For both methods, when the reaction was completed and hydrogen formation had

stopped, 10% molar excess of (3-glycidyloxypropyl) trimethoxysilane (GPS) (1.2 ml)

was introduced into the flask (chapter one, equation 1.12). In the molten reaction the

flask was stirred at 80 °C for five hours, however, in the solution method the

temperature was maintained at 50°C for five hours. After finishing reaction and

removing all solvent in the rotary evaporator the product was sealed under argon.

2. The second method was reaction between hydroxyl groups at both ends of PEG

and 3-aminopropyltriethoxysilane (APTES) (chapter one, section 1.4.2.1.2). In the first

step of reaction, di-carboxylic acid PEG had to be synthesized (chapter one, equation

1.16). 0.0025 of PEG 2000 Da (5 g) was weighed into the two necks round bottom flask

and dissolved in 175 ml toluene. PEG was dried at 130°C under argon by the azeotropic

distillation method and water collected with the Dean-Stark apparatus. The distillation

was continued until condensed toluene became clear. At room temperature 50% molar

excess of succinic anhydride based on PEG hydroxyl groups (0.75 g) was added to the

flask under argon. The reaction needed 1% molar ratio catalyst to promote the rate of

reaction and 4-dimethylaminopyridine (DMAP) (3 mg) was used as a catalyst. The

solution was stirred at 110oC for 5 hours. After solvent removal, for further purification

the product was dissolved in 50 ml of 2 M hydrochloric acid (HCl) to open the excess

succinic anhydride ring to form the water soluble carboxylic acid. Di-carboxylic acid

PEG was extracted by dichloromethane (DCM) from acidic solution in a separation

funnel. This purification procedure was repeated twice to be sure all unreacted succinic

anhydride was washed away.

61

In the second step of the reaction (chapter one, equation 1.17), 0.0025 mol of

dried di-carboxylic acid PEG (PEG 2000 Da 5.5 g) (dried again in toluene by the

azeotropic distillation method) was dissolved in 50 ml DCM under argon flow, then

30% excess molar ratio (based on moles of carboxylic acid) of 1-ethyl-3-(3-

dimethylaminopropyl) carbodiimide (EDC) (1.235 g) was separately mixed in dried

DCM and added into the flask. The complex of 4-(dimethylamino)pyridine (DMAP) and

p-toluenesulfonic acid (PTSA) (0.100 g)that had been previously synthesized was

mixed in DCM and added into the flask at room temperature. After 10 minutes stirring,

the last reagent 3-aminopropyltriethoxysilane (APTES) (1.2 ml) was introduced to the

solution at the same molar ratio as carboxylic acid. The stirring at room temperature was

continued overnight, however, the rate of this reaction was very fast.

3. The last method of synthesis of bis(trialkoxy silyl propyl) PEG was the reaction

between hydroxyl group of PEG and 3-(triethoxysilyl)propyl isocyanate (chapter one,

section 1.4.2.1.3). The 0.0025 mol of PEG (PEG 400: 1 g, PEG 2000: 5 g, PEG 4600:

11.5 g) was weighed in a two neck round bottom flask and dissolved in toluene (PEG

400: 60 ml, PEG 2000: 125 ml and PEG 4600 Da: 175 ml). PEG was dried by the same

azeotropic distillation method as mentioned above. At room temperature, 3-

(triethoxysilyl)propyl isocyanate (1.5 ml) was added to the flask under argon flow and

triethylenediamine (200 mg)as a catalyst was added. (The reaction mechanism with

tertiary amine catalysts was described in equation 1.24). The solution was stirred for at

least 40 hours under argon pressure at 85 °C in an oil bath. For purification of the

product, solvent was removed on a rotary evaporator. For further purification, the high

vacuum line was used to remove residual solvent and to sublime remaining catalyst, all

of which were collected in a liquid nitrogen trap. The product was sealed and stored

under argon.

2.2.2 Procedure for Synthesis of Polyethylene Oxide Silane with Different

Organic Chain Length

The procedure of synthesis of (methyl terminated) triethoxy silyl propyl

urethane-PEO was very similar to the procedure for reaction between hydroxyl group of

PEG and 3-(triethoxysilyl)propyl isocyanate, the only difference was in the amount of 3-

62

(triethoxysilyl)propyl isocyanate. This was because one end only of PEO has a hydroxyl

group compared to PEG that has two hydroxyl groups. All purification was exactly the

same as procedure that was mentioned in the previous section (section 2.2.1 part 3).

2.3 Synthesis of Bis acrylate Polyethylene glycol (PEG) (Acrylate Diesters of

PEG)

The mechanism of this reaction was described in chapter one, section 1.4.2.2.

The 0.0025 mole of PEG (PEG 2000 Da, 5 g and PEG 6000 Da, 15 g) was weighed in a

250 ml two neck round bottom flask. Benzene (around 175 ml) was used as a solvent.

Firstly, PEG was dried with the benzene azeotropic distillation method at 98 °C, as

previously mentioned (section 2.2.1 part 2). Triethylamine (distillated over ninhydrin

(C9H6O4)) in four times molar excess (2.8 ml) based on hydroxyl group of PEG was

added at room temperature. Acryloyl chloride, also in four times molar excess (1.6 ml)

based on PEG diol end groups, was added dropwise to the flask under an argon blanket

at room temperature. After adding all acryloyl chloride, the temperature was gradually

increased to 35 °C and the contents stirred for 24 hours [3]. In the purification

procedure, the product was firstly precipitated in chilled hexane (75 ml) to remove all

unreacted starting materials and was collected on a filter paper. For separation of

triethylamine and HCl salt from product, all products were dissolved in DCM (20 ml)

and filtered, then the solution part was added to sodium chloride solution in a separation

funnel, and this procedure was repeated twice. In the final stage of purification,

diacrylated PEG was dissolved in DCM (50 ml) and precipitated in chilled diethyl ether.

The product was collected on a filter paper and this separation procedure was repeated

four times. The final product was dried in vacuum oven at room temperature overnight

and stored in a freezer.

The same procedure of synthesis was attempted using toluene as solvent instead

of benzene, but the result was totally unsuccessful.

63

2.4 Network Synthesis Procedure

2.4.1 Reaction between Silica Surface and Chain End of PEG

2.4.1.1 Attempted Synthesis of Networks by Direct Reaction between Silica and

Bis(trialkoxy silyl propyl) PEG

Silica AEROSIL® 300 that was used has 7nm average diameter, four hydroxyl

groups per square nanometer with 300 m2/g surface area and 50 g/l density (supplier

datasheet). All calculations were based on complete reaction between silanol on the

surface of silica and six alkoxy groups on both ends of functionalized PEG (the reaction

mechanism was described inchapter one, section 1.6.2, equation 1.46). In the first step,

the calculated amount of silica (2 g) was weighed in a round bottom flask, and was dried

by the method that was given in section 2.1.1. For suspending dried silica 30 ml dried

THF (refluxed for 2 hour over potassium under argon pressure) or dried toluene was

added to the flask and the suspension was stirred at room temperature under argon. The

0.004 mol which is the calculated amount of bis(triethoxy silyl propyl urethane) PEG

(PEG 2000 Da, 8 g) was weighed in the absence of moisture and was added to the flask.

Five drops of triethylamine (Et3N) was added as a catalyst to accelerate the rate of

reaction. The suspension was stirred at 40 to 50 °C for 48 hours.

2.4.1.2 Attempted Synthesis of Networks with Direct Reaction between Silane-

modified Silica and PEG

The calculated amount of functionalized silica (2 g) (based on moles of PEG)

that was treated by (3-glycidyloxypropyl)trimethoxysilane (GPS) (as mentioned in

section 2.1.1) was dried at below 60 °C in a vacuum oven for two days to prevent ring-

opening of the epoxy groups and dispersed in dried toluene (50 ml) under argon. In the

next step, PEG (PEG 2000 Da 8 g) was weighed in a round bottom flask, and to it was

added the dianion of PEG that was previously synthesized in the method described in

section 2.2.1 part 1. This was dissolved in dried toluene under argon to help transfer all

the dianion PEG into the flask that contained functionalized silica. After mixing both

silica and PEG the flask was stirred at 50 to 60°C for 24 hours.

64

2.4.1.3 Attempted Synthesis of Networks by Direct Reaction between Amino-

silane-modified Silica and Bis Epoxy-PEG

In the first step in this method a modified silica which had primary amine (-NH2)

groups on the surface had to be synthesized. Aminopropyltriethoxysilane (APTES) was

used as the silane. Two different methods were used to synthesise the functionalized

silica:

• The first method was direct surface treatment of nano-silica which was discussed

in section 2.1.2.

• The other method was hybrid nano-silica synthesis. Firstly, 2.0 g of PEG-PPG-

PEG, Pluronic® P-123 (poly(ethylene glycol)-block-poly(propylene glycol)-block-

poly(ethylene glycol) with 5800 Da average molecular weight was dissolved in 15 ml

deionized water and 30g of 2M HCl was added in a 150 ml one neck round bottom

flask. The solution was stirred at 60 °C for 30 minutes. The flask was held in an

ultrasonic bath at room temperature for 30 minutes, then was stirred and equilibrated at

35 °C before adding the silane solution. In order to make silane solution, 4 g tetraethyl

orthosilicate (TEOS) and 0.5 g (3-aminopropyl) triethoxysilane (APTES) were mixed in

7.5 ml deionized water in a 100 ml one neck round bottom flask. Then 15 g of 2 M HCl

was added and stirred at 35 °C for 10 minutes. The silane solution was added to the

previous flask that contained acidic solution of Pluronic® P-123 at 35°C. The reaction

proceeded at 35 °C under nitrogen gas flow and was mixed for 24 hours. The suspension

was transferred to a Parr pressure vessel for aging at 85 °C for 48 hours. The aged

product was mixed with ethanol followed by further treatment in the ultra sonic bath for

1 hour. The suspension was heated at 60 °C overnight. The products were washed twice

with ethanol and filtered. The hybrid nano-silica was suspended for the third time in

ethanol and DCM (changed polarity of solvent) and hybrid nano-silica was separated by

centrifuging.

In the last step of the reaction procedure the calculated amount of functionalized

silica (2 g) was dispersed in water and ethanol mixture in a one neck round bottom flask,

then bis epoxy PEG ( PEG 1000 Da 4 g) was added to the flask. The suspension was

stirred for 48 hours at 80 °C.

65

2.4.2 Synthesis of Networks and Reinforced Networks with Hydrolysis and

Condensation Reactions

2.4.2.1 Procedure for Synthesis of Networks with and without Silica in Solutions

with Different pH

• In the synthesis of networks without any added silica as discussed in chapter one,

Table 2. 1. Quantities of reagents used for in situ silsesquioxane PEG networks

Sample Name

PEG Precursor (Mn, wt.)

Methanol (g)

Silica (g)

Water (ml)

HCl (M, ml)

HN4OH (M, ml)

PEG2000SW1 2000 Da, 0.25 g 0.15 0 0.15 0.1 M, 0.05 ml 0

PEG2000SW2 2000 Da, 0.25 g 0.15 0 0.15 0.1 M, 0.10 ml 0

PEG2000SW3 2000 Da, 0.25 g 0.15 0 0.15 0.1 M, 0.150 ml 0

PEG2000SW4 2000 Da, 0.25 g 0.15 0 0.15 0.1 M, 0.200 ml 0

PEG2000SW5 2000 Da, 0.25 g 0.15 0 0.15 0 0.01 M,

0.150 ml

PEG400SW1 400 Da, 0.25 g 0.15 0 0.15 0.1 M, 0.250 ml 0

PEG400SW2 400 Da, 0.25 g 0.15 0 0.15 0.1 M, 0.500 ml 0

PEG400SW3 400 Da, 0.25 g 0.15 0 0.15 0.1 M, 0.750 ml 0

PEG400SW4 400 Da, 0.25 g 0.15 0 0.15 0.1 M, 1.00 ml 0

PEG2000SH1 2000 Da, 0.30 g 0.34 0 0.15 0.001 M, 0.05 ml 0

PEG2000SH2 2000 Da, 0.30 g 0.34 0 0.15 0.01 M, 0.05 ml 0

PEG2000SH3 2000 Da, 0.30 g 0.34 0 0.15 0.05 M, 0.05 ml 0

PEG2000SH4 2000 Da, 0.30 g 0.34 0 0.15 0.2 M, 0.05 ml 0

PEG400SH1 400 Da, 0.30 g 0.34 0 0.15 0.001 M, 0.25 ml 0

PEG400SH2 400 Da, 0.30 g 0.34 0 0.15 0.01 M, 0.25 ml 0

PEG400SH3 400 Da, 0.30 g 0.34 0 0.15 0.05 M, 0.25 ml 0

PEG400SH4 400 Da, 0.30 g 0.34 0 0.15 0.2 M, 0.25 ml 0

PEG4600SH1 4600 Da, 0.30 g 0.34 0 0.15 0.001 M, 0.0225 ml 0

PEG4600SH2 4600 Da, 0.30 g 0.34 0 0.15 0.01 M, 0.00225 ml 0

PEG4600SH3 4600 Da, 0.30 g 0.34 0 0.15 0.05 M, 0.00225 ml 0

PEG4600SH4 4600 Da, 0.30 g 0.34 0 0.15 0.2 M, 0.00225 ml 0

66

section 1.5.2, in the first step of reaction the calculated amount of bis(triethoxy silyl

propyl urethane)-PEG precursor (synthesized by the procedure of section 2.2.1 part 3)

was dissolved in methanol in a polypropylene sample tube with cap. All quantities of

reagents are given in table 2.1.After agitation in the ultrasonic bath for 5 minutes the

sample tube was heated in an oven at 50 °C for about 6 hours to evaporate the methanol.

Deionized water was added to the sample tube which was kept in saturated humidity

condition at 38 °C overnight.

In samples PEG2000SH2TS, PEG2000SH3TS, PEG4600SH2TS and

PEG4600SH3TS 28.9 μmol TEOS (6.5 mg) was added into bis(triethoxy silyl propyl

urethane)-PEG solutions (methanol as a solvent). The rest of the reagents and reaction

condition and procedure were the same as samples PEG2000SH2, PEG2000SH3,

PEG4600SH2 and PEG4600SH3.

Then depending on the experiment design, different acid concentrations (HCl) or

different volume of hydrochloric acid or ammonium hydroxide solution (table 2.1) was

added to the sample tube and completely mixed to synthesise homogeneous networks.

The solution was left in an oven overnight at 45 °C and 24 hours at 50 °C to further the

condensation reaction. In PEG400 and PEG4600SH samples this time was longer for

further hydrolysis reaction, as mentioned in chapter one, section 1.5.2.1.2. The sample

was moved to the vacuum oven at 60 °C for at least 48 hours under full vacuum for post

cure.

• In the synthesis of networks with dangling chains, in the first step of reaction the

calculated amount of bis(triethoxy silyl propyl urethane)-PEG 2000 precursor

(synthesized by the procedure of section 2.2.1 part 3) and triethoxy silyl propyl urethane

-PEO 2000 precursor (synthesized by the similar procedure of section 2.2.1 part 3 with

PEO 2000) were dissolved in methanol in a polypropylene sample tube with cap (all

quantities of reagents in table 2.2).

After agitation in the ultrasonic bath for 5 minutes the sample tube was heated in

an oven at 50 °C for about 6 hours (methanol evaporation). Deionized water was added

to the sample tube which was kept in saturated humidity condition at 38 °C overnight.

67

The rest of synthesis procedure was exactly the same as the synthesis method without

silica which was discussed in the previous section.

Table 2. 2. Quantities of reagents used for in situ silsesquioxane PEG2000 networks

with different percentage of dangling chain

Sample Name

PEG 2000 Precursor

(g)

PEO 2000 Precursor

(%, wt.) Methanol

(g) Water (ml)

HCl (M, ml)

PEG2000SWD0 0.25 0, 0 g 0.15 0.15 0.1 M, 0.150ml

PEG2000SWD1 0.2475 1%, 0.0025 g 0.15 0.15 0.1 M, 0.150ml

PEG2000SWD5 0.2375 5%, 0.0125 g 0.15 0.15 0.1 M, 0.150ml

PEG2000SWD10 0.225 10%, 0.025 g 0.15 0.15 0.1 M, 0.150ml

PEG2000SWD15 0.2125 15%, 0.0375 g 0.15 0.15 0.1 M, 0.150ml

PEG2000SWD20 0.2 20%, 0.05 g 0.15 0.15 0.1 M, 0.150ml

• In the synthesis of networks in the presence of silica (chapter one, section 1.6.2,

equation 1.45), in the first step the calculated amount of silica that depended on the

desired percentage of silica in the final reinforced network was weighed in a

polypropylene sample tube with cap and methanol (all quantities of reagents in table

2.3) was added to the tube.

The sample tube was agitated in the ultrasonic bath for 30 minutes up to an hour

until all the silica completely dispersed in methanol. The calculated amount of

bis(triethoxy silyl propyl urethane)-PEG (table 2.3) was added to the suspension

followed by further treatment in the ultrasonic bath for 15 minutes. The sample tube was

placed in the oven at 50 °C for about 6 hour. Deionized water was added to sample tube

and was kept in saturated humidity condition at 38 °C overnight. The rest of the

synthesis procedure was exactly the same as the synthesis method without silica which

was discussed in the previous section.

68

Table 2. 3. Quantities of Reagents Used for in situ silsesquioxane PEG Networks

with silica

Sample Name

PEG Precursor (Mn, wt.)

Methanol (g)

Silica (%, wt.)

Water (ml)

HCl (M, ml)

PEG2000SWS0 2000 Da, 0.5 g 0.3 0, 0 0.3 0.1 M, 0.300 ml

PEG2000SWS1 2000 Da, 0.495 g 0.3 1%, 0.005 g 0.3 0.1 M, 0.300 ml

PEG2000SWS5 2000 Da, 0.475 g 0.3 5%, 0.025 g 0.3 0.1 M, 0.300 ml

PEG2000SWS10 2000 Da, 0.450 g 0.3 10%, 0.05 g 0.3 0.1 M, 0.300 ml

PEG2000SWS20 2000 Da, 0.4 g 0.3 20%, 0.1 g 0.3 0.1 M, 0.300 ml

PEG400SWS0 400 Da, 0.5 g 0.3 0, 0 0.3 0.1 M, 1.500 ml

PEG400SWS1 400 Da, 0.495 g 0.3 1%, 0.005 g 0.3 0.1 M, 1.500 ml

PEG400SWS5 400 Da, 0.475 g 0.3 5%, 0.025 g 0.3 0.1 M, 1.500 ml

PEG400SWS10 400 Da, 0.450 g 0.3 10%, 0.05 g 0.3 0.1 M, 1.500 ml

PEG400SWS20 400 Da, 0.4 g 0.3 20%, 0.1 g 0.3 0.1 M, 1.500 ml

PEG400SH1S5 400 Da, 0.475 g 0.3 5%, 0.025 g 0.3 0.001 M, 1.500

ml

PEG400SH2S5 400 Da, 0.475 g 0.3 5%, 0.025 g 0.3 0.01 M, 1.500 ml

PEG400SH3S5 400 Da, 0.475 g 0.3 5%, 0.025 g 0.3 0.05 M, 1.500 ml

PEG400SH4S5 400 Da, 0.475 g 0.3 5%, 0.025 g 0.3 0.2 M, 1.500 ml

2.4.3 Procedure of Synthesis of Networks from Bis acrylate PEG with and

without Silica

• The first procedure in synthesis of networks is without silica ie. neat networks

(free radical reaction mechanism was described in chapter one, section 1.5.1). The

calculated amount (0.700 g) of bis acrylate PEG (2000 and 6000) was weighed in a glass

vial and 0.700 g methanol was added as a solvent. The vial was agitated in the ultra

sonic bath for 10 minutes in order to completely dissolve the polymer. To the solution,

3.5 mg of α,α-dimethoxy-α-phenylacetophenone was added as an UV initiator (chapter

one, equation 1.27). The solution was agitated in the ultrasonic bath for 5 minutes and

69

degassed under vacuum for 2 hours. The solution was poured into a quartz-slide mould

in order to make networks in precise shape which was suitable for dynamic mechanical

analysis measurement (chapter one, section 1.8). Both sides of the mould containing the

polymer solution was exposed to UV light for 30 minutes. In order to post cure the

sample, the mould was moved into a nitrogen bag and kept at 55 °C overnight. The

network was then removed from the nitrogen bag to evaporate methanol. The networks

were dried in vacuum oven for at least 5 days.

The next procedure in synthesis of reinforced networks is with silica which had

different surface chemistry. For functionalized silica, the percentage of organic material

was considered, in order to achieve an equal amount of silica in each sample. In the first

step the calculated amount of neat or functionalized silica was weighed in a glass vial

and methanol was added to the tube (all quantities of reagents in table 2.4). The vial was

Table 2. 4. Quantities of reagents used for bis acrylate PEG2000 networks with and

without silica

Sample Name

Type of Silica

Silica (%, wt.)

Methanol (g)

PEG Precursor

(g) Initiator

(mg)

PEG2000AS0 - 0, 0 g 0.7 0.7 g 3.5

PEG2000AS2 A300 2%, 0.014 g 0.7 0.686 g 3.5

PEG2000AS10 A300 10%, 0.07 g 0.7 0.63 g 3.5

PEG2000AS20 A300 20%, 0.14 g 0.7 0.56 g 3.5

PEG2000AV-S20 Vinyl-Silica 20%, 0.147 g 0.7 0.56 g 3.5

PEG2000AP-S20 Propyl-Silica 20%, 0.147 g 0.7 0.56 g 3.5

PEG2000APEO-S20 PEO-Silica 20%, 0.182 g 0.7 0.56 g 3.5

PEG2000APEO20-S20 PEO 2000-

Silica 20%, 0.183 g 0.7 0.56 g 3.5

agitated in the ultrasonic bath for 30 minutes up to several hours until all silica was

completely dispersed in methanol. The calculated amount of bis acrylate PEG was

added in to the suspension. The vial was agitated in the ultrasonic bath for 10 minutes in

order to dissolve the polymer completely in methanol and silica was completely

70

dispersed into the polymer matrix. The rest of the synthesis procedure was described in

the previous part for synthesis of neat network.

2.5 Sol Fraction Measurement

Firstly, networks were dried in vacuum oven for at least 10 days and the dried

samples were weighed before immersing in water. The networks were immersed into

water in gooch glass crucibles at 50 °C in an oven for 5 days. Water was replaced twice

each day with pre-heated water at 50 °C very carefully, because some swollen hydrogels

had fallen apart.

The swollen hydrogels firstly were dried in oven at low temperature, after 24

hours they were placed in vacuum oven and drying in vacuum oven was continued until

the weight of samples became constant. All dried samples were stored in desiccators for

cooling before weighing. All dried networks were weighed and sol fractions were

calculated.

2.6 Swelling Measurement

Dried networks were weighed and immersed in the swelling agents that were

either silicone-rake methyl terminated PEG copolymer or water. The swollen gels were

accurately weighed with time and after each weighing the samples were returned to the

swelling agent. This procedure was continuing until the weight change between

measurements became zero within experimental error.

2.7 Characterization Techniques and Instruments

2.7.1 Differential Scanning Calorimetry (DSC)

Differential scanning calorimetry (DSC) was used in this research in several

different modes. TA Instruments DSC Q100 instrument was employed under 40

mL.min-1 flow rate of nitrogen. The amount of sample was below 4 mg and was

accurately weighed and sealed in aluminum pans and lids. The modes of running are

described:

• The first mode was melting point measurement for which a Heat/Cool/Heat cycle

was applied. The samples were equilibrated at 100 °C for 2 to 5 minutes to melt all

71

crystals, samples were cooled at 5 °C per minutes down to -80 °C, then they were heated

from -80 °C to 100 °C at 10 °C per minutes. Tm and melting enthalpy values which were

calculated with integration of heat flow curve were obtained. These melting enthalpy

values were used to determine percentage crystallinity.

• The next mode was for glass transition temperature (Tg) measurement. For this

measurement three different procedures were used. The first procedure was a rapid

Heat/Cool/Heat cycle. The samples were equilibrated at 100 °C for 2 to 5 minutes to

remove all crystal and thermal histories, the samples were rapidly cooled down to -80

°C, and after reaching this temperature, samples were heated up to 100 °C at 20 °C per

minute. The second method was Modulated DSC runs in which the rate of heating was

10 °C per minute with ±0.5°C per minute oscillations.

• The last mode of DSC running was step crystallization (SC) fractionation method

(as described in chapter 1, section 1.7.2). In this mode the experiment was run in

heat/cool/heat cycle. The sample was equilibrated at 100°C for 2 min, and was then

cooled stepwise. Each step temperature had -4 °C decline and was held for at least 30

minutes. The temperature was decreased until all crystalline regions were formed. The

sample was then heated up to 100 °C at 5 °C per minute.

2.7.2 Fourier Transform Infrared (FT-IR)

FTIR-ATR and transmission FTIR were the two different types of FTIR

experiments that were used.

• Transmission FTIR was run in a Nicolet Nexus spectrometer with the sample as a

thin film between two KBr discs. A thin film was formed with polymer solution and the

sample was run for 16 scans with 4cm-1 resolution. Background was run in the same

condition with the clean KBr discs.

• FTIR-ATR experiment was run in a Nicolet Nexus spectrometer which was

equipped with a Diamond ATR accessory. The spectral region was from 4000 to 525

cm-1 with 4cm-1 resolution. To obtain a satisfactory level of signal to noise all samples

were run for 64 scans. Background was run in the same setting as the sample setting.

72

2.7.3 FT-Raman Spectroscopy

A Perkin-Elmer system 2000 NIR FT-Raman spectrometer equipped with Nd-

YAG laser source with λ=1064 nm wave length for excitation and InGaAs photoelectric

detector. The samples were run for 16 or 32 scans.

2.7.4 Gel Permeation Chromatography (GPC)

2.7.4.1 Analytical GPC

Size exclusion separation was performed on a GPC Waters Breeze system model

151 with an isocratic HPLC pump and eluted fractions were detected with refractive

index detector Waters model 2414. Three columns Phenomenex, phenogel (5μ - 50 Å,

5μ - 103 Å and 5μ - 104 Å) were used for size exclusion separation. The mobile phase

was THF with 1 ml/min. flow rate at 30 °C. A 200 μl sample having a concentration of 5

mg/ml in THF was injected into the GPC instrument after filtration with 0.4 μ Teflon

syringe-type filter.

2.7.4.2 Preparative GPC

For large scale silicone copolymer separation an Agilent 1200 series Preparative

pump HPLC/GPC with UV detector and fraction collector was employed. The flow rate

was 5 ml/min. in THF as mobile phase at room temperature, 900 μl sample with a

concentration of 75 mg/ml in THF was injected. Separation was done with a

Phenomenex preparative column and fractions were collected based on time determined

from analytical GPC.

2.7.5 Dynamic Mechanical Test (DMTA)

Dynamic mechanical tests were performed with Mettler Toledo

DMA/SDTA861e instrument. The test was run in tensile (sample shape was bar

2×4×10.5mm) and compression (cylindrical shape) modes at 5 Hz from -90 to 50 °C

with a temperature ramp of 2 °C/min (using liquid nitrogen as cooling system). The

settings for each sample were obtained with an isothermal (25 °C) run.

73

2.7.6 Nuclear Magnetic Resonance (NMR)

A Bruker 400 MHz spectrometer with a broadband liquid probe was used. In this

research 1H NMR, 13C NMR and 2D NMR was performed on samples in liquid (CDCl3

and D2O) and gel (swollen in CDCl3) states. A Varian 400 MHz with solid state probe

with 4mm rotor was also used. Solid state NMR spectra were collected for 29Si nuclei.

1. In liquid state, 1H NMR, 13C NMR and 2D NMR depends on polymer molecular

weight (400 to 10000Da) so from 5 to 50 mg sample was dissolved in CDCl3 and

filtered.

2. In gel 1H NMR, polymer was cut into small strips, and immersed in CDCl3

(around 10% wt./wt.). The NMR experiment was run with 32 scans.

3. In 29Si solid state NMR, the ground polymer sample was loaded into the rotor.

Magic angle spinning at 3500Hz with 1H decoupling and cross polarization was

employed. The NMR experiment was run for 25500 scans.

2.7.7 Thermogravimetric Analysis (TGA)

To measure the percentage of silsesquioxane groups in the PEG networks, small

quantities of the dry networks (10 mg) were put in a platinum pan for analysis on a TA

Instrument (TGA Q500) under a flow of nitrogen up to 450oC at 5oC/min. heating rate

and then under oxygen up to 1000oC at the same rate.

References

1. Lin, J., Siddiqui, J. A. and Ottenbrite, R. M., Surface Modification of Inorganic Oxide Particles with Silane Coupling agent and Organic dyes. Polym. Adv. Technol., 2001. 12: p. 285-292.

2. Allmer, K., et al., Surface modification of polymers. V. Biomaterial applications. Journal of Polymer Science Part A: Polymer Chemistry, 1990. 28(1).

3. Cruise, G.M., Hegre, O. D., Scharp, D. S. and Hubbell, J. A., A Sensitivity Study of the Key Parameters in the Interfacial Photopolymerization of Poly(ethylene glycol) Diacrylate upon Porcine Islets. Biotechnology and bioengineering, 1998. 57(6): p. 655-665.

74

Chapter 3: Synthesis of Novel poly (ethylene

glycol) Based Networks with Formation of in

Situ Silsesquioxane Crosslinkers

3.1 Introduction

As mentioned in chapter one, section 1.4.2, for synthesis of networks, the

hydroxyl end groups of PEG need to be changed to active chemical groups such as

diacrylate- or bis(triethoxy silyl)-PEG (PEG precursors). In this chapter, PEG network

formation through Si-O-Si linkages will be discussed. There are several possible

synthetic routes to form these Si-O-Si linkages. The first possible synthesis strategy is a

direct reaction in absolute dry conditions between either bis(triethoxy silyl)-PEG and

silica or functionalized silica and PEG. In this method silica acts as a crosslinker to form

organic-inorganic reinforced PEG-based networks. The other possible synthesis strategy

is sol-gel reaction with bis(triethoxy silyl)-PEG precursor either with or without

additional TEOS.

As mentioned in chapter one, section 1.3.1.1, network swelling and de-swelling

and properties are related to crosslink structures (Si-O-Si linkage structures). In this

chapter a novel method of synthesis will be developed to control networks properties

with sol-gel reaction conditions. To better understand the structures of in situ

silsesquioxane crosslinker and PEG networks from different methods of synthesis, the

thermal behaviour of dry network as well as 29Si solid state NMR results will be

investigated in detail. Direct imaging of the silica domains is not possible because they

are present at low concentration (5.5 wt % by TGA) and are beyond the resolution of

electron microscopy. The issue of whether the silsesquioxane may be regarded as a

phase separated system or the network is held together through silsesquioxane units is

discussed later.

75

3.2 Synthesis, Results and Discussion of Network formation

3.2.1 Synthesis of Bis(trialkoxy silyl)-PEG Precursor

As mentioned in chapter one, section 1.4.2.1, and chapter two, section 2.2, there

are three methods to synthesise bis(trialkoxy silyl) PEG:

3.2.1.1 Reaction between 3-glycidoxypropyl trimethoxylsilane (GPS) and PEG

The first step is synthesis of anion groups at both ends of PEG (equation 1.11).

The critical point in this synthesis is the amount of sodium hydride (NaH). Insufficient

NaH can leave some hydroxyl groups which are inactive, however, too much NaH can

react with epoxy ring groups in silane in the next step, and deactivate GPS. This is the

one disadvantage of this method. Due to the high activity of dianion PEG groups, the

reaction can be reversed with exposure to moisture, so it is difficult to determine the

reaction yield.

The second step is the reaction between the dianion of PEG and the epoxy group

of the silane in absolutely dry conditions (equation 1.12). For monitoring the reaction, 1H NMR has been applied to PEG, GPS and bis(trimethoxy silyl)-PEG. The 1H NMR of

PEG in CDCl3 is shown in Figure 3. 1. Peaks from 3.6 to 3.8 ppm are for protons in the

backbone, the peak around 2.5 ppm is hydrogen in the hydroxyl groups at end of PEG.

Figure 3. 2 is 1H NMR spectrum of (GPS) in which peaks at 2.6, 2.8 and 3.2 ppm are for

three hydrogens in epoxy ring, and that at 3.6 ppm is for methyl group hydrogen in tri

methoxyl groups. The peaks at 0.7, 1.7 and 3.5 ppm are for protons in first, second and

third carbons adjoining silicon [1].

As shown in the 1H NMR spectrum of functionalized PEG Figure 3. 3, the

proton peaks of epoxy in GPS (peaks at 2.6, 2.8 and 3.2 ppm) and proton peak of

hydroxyl group in PEG (2.5 ppm) have disappeared indicating that reaction has taken

place.

As mentioned before, this method of synthesis is sensitive to amount of NaH

either under or higher than the stoichiometric ratio. For tackling this issue the method of

synthesis was changed to explore different ways of reaction between organosilanes of

different structure and hydroxyl end groups of PEG.

76

Figure 3. 1. 1H NMR spectrum of PEG in CDCl3

Figure 3. 2. 1H NMR spectrum of 3-glycidoxypropyl trimethoxylsilane (GPS).

77

Figure 3. 3. 1H NMR of bis(trimethoxy silyl propyl)-PEG with GPS in CDCl3,

compared to PEG and GPS.

3.2.1.2 Reaction between 3-aminopropyltriethoxysilane (APTES) and PEG

In this reaction amine group at end of (APTES) reacts with dicarboxylic acid

functionalized PEG to produce amide linkage group between silane and PEG ends.

As discussed in chapter one, section 1.4.2.1.2, and chapter two, section 2.2, the

first step in this reaction is synthesis of carboxylic acid-terminated PEG by reaction

between succinic anhydride and PEG with (DMAP) as a catalyst which there is no by-

product in this reaction as shown in equation 1.16 [2].

After completion of the reaction, the extra succinic anhydride and catalyst must

be removed with acidic water and DCM (as explained in chapter two section 2.2). The

final product can be tested with 1H NMR to check conversion and purity of dicarboxylic

acid-terminated PEG as shown:

78

Figure 3. 4. 1H NMR spectrum of dicarboxylic acid-terminated PEG.

In the 1H NMR spectrum Figure 3. 4, protons (8H) between two carboxyl groups

at both ends of polymer chains appear at 2.6 ppm, and protons (4H) of PEG that are

located next to carboxyl group in each side appear at 4.25 ppm. Since succinic

anhydride protons are at 3.0 ppm the 1H NMR spectrum proves the purification was

completely done (based on 1H NMR sensitivity) [3].

The next step is reaction between dicarboxylic acid-terminated PEG and

(APTES) in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)

and complex of (DMAP) and p-toluenesulfonic acid (PTSA) as catalyst (equation 1.17).

This reaction generates urea (from EDC) as by-product. These by-products and complex

catalyst residues are impurities that can affect the next step of reaction (either silica

surface modification reaction or sol-gel reaction). The problem of purification is the

sensitivity of silanols at both end of dicarboxylic acid- terminated PEG. To tackle this

issue, instead of amide linkage reaction, the urethane linkage reaction method was used.

79

3.2.1.3 Reaction between 3-(triethoxy silyl)propyl isocyanate and PEG

This method of synthesis has been used for all bis(triethoxy silyl propyl

urethane) PEG precursor in this research, due to there being no by-product and this

method needs only solvent evaporation and catalyst sublimation.

As discussed in chapter one, section 1.4.2.1.3 and chapter two, section 2.2,

reaction between 3-(triethoxysilyl)propyl isocyanate as an organosilane source and PEG

occurs in the presence of tertiary amine catalyst under dry and inert atmosphere. The

different mechanisms with different catalysts were discussed in section 1.4.2.1.3. By

reason of the low efficiency of polymer end-group reaction, excess of silane needs to be

applied, however, during catalyst sublimation under high vacuum the fraction of

unreacted silane can be removed from the final product. However, residual unreacted 3-

(triethoxysilyl) propyl isocyanate reacts with silane group at polymer ends to help to

form in situ silsesquioxane crosslink during sol-gel reaction.

The reason for the over-stoichiometric ratio of organosilane is the very high

molecular weight of the polymer and thus the low molar concentration of end-groups.

The reaction is followed by FTIR and the silane end group is tested with 29Si

Solid State NMR. In Figure 3. 5, FT-IR shows a spectrum of mixture of PEG and 3-

(Triethoxysilyl) propyl isocyanate and of bis(triethoxy silyl propyl urethane) PEG. The

stretching band of the unreacted NCO (isocyanate) appears at 2270 cm-1 and after the

reaction has taken place, the carbonyl for urethane (C=O stretching in urethane) appears

at 1740 to 1700 cm-1 [4] and the –NH bend of the urethane occurs at around 1530 cm-1.

13C NMR demonstrates conversion of starting material to precursor by the

disappearance of signals at 72.5 ppm (OCH2CH2OH) and 61.5 ppm (OCH2CH2OH) and

appearance of signals at 156.2 ppm (C=O in the urethane bond), at 69.5 ppm

(OCH2CH2OCONH)and 63.6 ppm (OCH2CH2OCONH). Assignments were confirmed

with 2D proton-carbon HSQC.

29Si Solid State NMR spectrum of bis(triethoxy silyl propyl urethane) PEG

shows T0 (-CH2Si(OC2H5)3) (Figure 3. 6). It shows there is no T1 to T3 (T1, T2 and T3 in 29Si Solid

80

Figure 3. 5. FTIR spectrum of bis(triethoxy silyl propyl urethane)-PEG (lower

black line) compared to that of the reagents (upper red line) before reaction.

Figure 3. 6. 29Si Solid State NMR spectrum of bis(triethoxy silyl propyl urethane)-

PEG showing band at -46 ppm attributed to T0 (-CH2Si(OC2H5)3).

81

State NMR are -50, -59 and -64 ppm, respectively) which confirms the bis(triethoxy

silyl propyl urethane) PEG is a precursor without any crosslinking reaction. The reason

that the sol-gel reaction has not started is because the precursor is stored under argon in

a completely dry condition to prevent any hydrolysis reaction which would be followed

by a condensation reaction.

3.2.2 Synthesis of Networks by Reaction between Hydrophilic Silica Surface and

Bis(triethoxy silyl propyl urethane)-PEG in Dry Conditions (The First

Possible Synthesis Strategy)

Silanols on the surface of silica can directly react with alkoxide groups at both

ends of bis(triethoxy silyl propyl urethane) PEG with alcohol condensation reaction

(equation 1.46) without any hydrolysis reaction in the absence of water ie. under

absolute dry conditions (as was discussed in section 1.6.2). This surface reaction which

makes Si-O-Si bonds at the interface of silica and PEG can potentially make three

dimensional networks in which silica acts as the crosslinker element. The advantage of

these types of networks is that there has been direct synthesis of a nano-silica composite

with an active filler having a covalent bond between silica and polymer chains.

These types of reaction can be designed in two major ways: the first method is

synthesis of bis(triethoxy silyl propyl urethane)-PEG and reaction with silanols on the

surface of silica. The second method is functionalizing the surface of silica with an

organosilane, followed by reaction between the organic tail of the organosilane on the

surface of silica and end groups of PEG (either hydroxyl groups or other active groups

such as amine or epoxy).

If both of these methods work, and there is a sufficient number of three-

dimensional Si-O-Si bonds produced during reaction, the viscosity of this suspension

(silica, polymer and solvent) must increase and ultimately the suspension change to a

crosslinked network. However, as described in the following section, in both methods of

synthesis networks were not produced. For finding out the reasons behind these

unsuccessful synthesis methods, several studies were performed.

82

3.2.2.1 Reaction between Hybrid Silica and PEG with Epoxy End Groups

In the first step amino-functionalized hybrid silica was synthesized, following

the method of synthesis and purification as described in chapter two, section 2.4.1.3.

The silica after soxhlet extraction with tetrahydrofuran (THF) was examined with 29Si

Solid State NMR. The reason for the synthesis of amino-functionalized hybrid silica was

to achieve a controlled number of primary amine groups on the surface of silica.

Increasing the number of active groups can raise the number of attached polymer chains

on the surface of silica without surface modification. This hybrid silica can be used as a

model to show the effect of silica as crosslinker. The 29Si Solid State NMR spectrum is

shown:

Figure 3. 7. 29Si Solid State NMR of amino-functionalized hybrid silica. Silica

structures corresponding to T2, T3, Q3 and Q4 are seen at -59, -68, -102 and -110

ppm, respectively.

The 29Si NMR spectrum in Figure 3. 7 clearly shows the hybrid silica synthesis

was successfully done and there are mostly T3 species from 3-

aminopropyltriethoxysilane (APTES). It also shows Q4 and Q3 silicon species dominate

and there is not very much Q1 and Q2 which means the silica structures are dense. The

83

synthesis occurred in the presence of water and HCl (sol-gel reaction), so as a result,

APTES can react with itself as well as with TEOS. There is also the possibility APTES

reacted together and made very small particles with linear or cage structures, which

were washed away during the soxhlet extraction with THF.

In the next step of the reaction di-epoxy PEG (1000 Da) was added to a

suspension of the hybrid silica in the presence of ethanol as a catalyst. In this reaction,

the viscosity did not increase so it was concluded that the suspension was not changed to

a three-dimensional network.

3.2.2.2 Model Reaction by Applying Organosilanes with Different Organic

Groups

Based on the random coil theory, the ends of polymer chains most of the time

stay within a certain distance which is far shorter than the fully stretched polymer chain

length (contour length). The end-of-chain reaction is controlled by diffusion which is

limited by the polymer coil. When one end of polymer chain reacts with surface of

hydrophilic silica, the chain chemically binds to silica surface and the rest of the chain

cannot move freely in the solution. The polymer chain covers the area around the bond

on the surface (shown schematically in Figure 3. 8).

Figure 3. 8. Attached polymer random coil around silica particle.

84

This coverage can be enhanced if the backbone of the chain can make hydrogen

bonds with silanols (Figure 3. 9) [5]. All these phenomena can cause difficulties in the

complete interface reaction. However, the yield of silica surface functionalization

reaction with an organosilane with very short organic tail is rather low. This is discussed

below and has been proven by 29Si NMR.

Figure 3. 9. Hydrogen bonding between silanols on the surface of silica and

backbone of PEG.

To explore the effect of the organic tail of silane on the reaction, several

different silanes with different chemistry and length of the organic tails were used.

Several types of triethoxy silyl propyl urethane-PEO with one side methyl-terminated

and with different molecular weights were synthesized. (This reaction is the same as

urethane linkage reaction which was discussed in section 3.2.1.3).

All these reactions were done under the same conditions, except for triethoxy

silyl propyl urethane-PEO2000 in which the solvent was changed from toluene to DCM

(chapter two, section 2.1.1). This change was done due to hydrogen bonding effects on

the functionalization reactions. Toluene is not a very good solvent for PEG, but DCM is

a very good solvent which means the radius of gyration (Rg) of PEG in toluene

compared to DCM solvents is smaller, since interactions between polymer and solvent

85

can change the radius of gyration (Rg). The interaction of solvent and PEO can also

change interaction between PEO and silanol groups on the surface of silica. In other

words, DCM can reduce the hydrogen bonding which is shown in Figure 3. 9. A

reflection of this solvent change is the change in the yield of functionalization in both

DCM1 and 2 silica where were explained in chapter two, section 2.1.1.

SiOH3CO

O

H3C

H3C

CH3

SiO

O

O

CH2

H3C

H3C

H3C

SiO

O

O

H3C

H3C

H3C

OOCH3

n

5

SiO

O

O

H3C

H3C

H3C

CHN O

OCH3O

n=14 and 45

Triethoxyvinylsilane

Trimethoxy(propyl)silane

TriethoxyPEOsilane

TriethoxyPEOsilane (urethane linkage)

TEA

Tolueneor

DCMSi

OO

Si O Si C

SiO

RO

Alcohol

Silica

Product

(3.1)

3.2.2.2.1 Characterization of Functionalized Silica with Different Silanes

For illustration of the effects of polymeric tails of organosilanes,

thermogravimetric analysis (TGA) and 29Si Solid State NMR were applied to investigate

the effects of changes in the reactions. The chemical linkages between silica surface and

silane can be examined with 29Si Solid State NMR and the amount and number of

linkage can be measured with TGA.

Figure 3. 10 illustrates the weight changes with temperature for different organic

tails in organosilanes. If the weight loss is expressed in terms of mole loss, it can

represent average number of molecules attached per 100 g of different types of

86

functionalized silica. In Figure 3. 11 this is clearly shown since the moles lost increase

with decrease of organic tail length of organosilane as discussed in section 1.5.2. When

this tail has interaction with the surface of silica, it hinders the access of the chain end to

the surface and react with the surface. The other factor that can control the number of

chains attached to the surface of silica is the viscosity.

Figure 3. 10. Thermogravimetric analysis (TGA) results for different

functionalized silica.

When several chains are attached next to each other and to the surface of the

same silica particle, the organic chains with greatest length have more entanglements

which cause the viscosity to increase. This viscosity can change with different solvents,

and ultimately can change the number of anchored chains; however, it cannot be very

effective near silica surface to increase this number. This is because the flexibility of

chains that are attached to surface of silica decreases due to covalent bonding between

87

silane part of chains and surface of silica. As a result, diffusion rate of chain ends near

the surface of silica decreases dramatically (as shown schematically in Figure 3. 8).

Figure 3. 11. Moles of different silanes that are attached to 100 g functionalized

silica when treated by different silanes.

For testing this viscosity and diffusion controlling effects on reaction between

silica and triethoxy silyl propyl urethane-PEO 2000 reactions DCM 1 and DCM2 were

examined. Both DCM1 and DCM 2 syntheses were done in DCM as solvent (chapter

two, section 2.1.1 and shown schematically in Figure 3. 12 a and b). However,

differences between these two methods are in the way of adding triethoxy silyl propyl

urethane-PEO2000 to the reaction flask which were explained in chapter two section

2.1.1. In DCM 1 method all reagents (dried silica, dried DCM, tertiary amine and

triethoxy silyl propyl urethane-PEO2000) were introduced to the flask under argon. In

contrast, in DCM 2 method all reagents except triethoxy silyl propyl urethane-PEO2000

were placed into a flask in absolute dry condition under argon, triethoxy silyl propyl

urethane -PEO2000 solution in DCM was added dropwise to the suspension with a

pressurized dropwise funnel during 4 hours. The reason these two methods of

88

experiment were done is to minimize hydrogen bonding and interactions between silica

surface and triethoxy silyl propyl urethane-PEO2000 in the very early stage of the

reaction in the DCM 2 method (Figure 3. 12 b) When the concentration of triethoxy silyl

propyl urethane-PEO2000 is lower, the silane end of the chain diffuses easier compared

to when the concentration is higher. The reaction is also controlled by entanglement

between PEO chains. The number of entangments which hinders diffusion increases

with polymer concentration and the chain ends have a lower probeblity to reach to an

Figure 3. 12. (a) Schematic highlighting the diffusion limitations in DCM1 model.

(b) Schematic of DCM 2 model and reaction between surface and triethoxy silyl

propyl urethane-PEO2000.

active silanol site on the silica surface. The other factor is hydrogen bonding between

silanol and PEO backbone at high concentration of polymer. At lower concentration

89

hydrogen bonding takes place, and silane end groups can reach to free silanol easier and

condensation occurs.

Figure 3. 13. 29Si Solid State NMR (CP) for (a) Silica A300, propyl-Silica and vinyl-

Silica (b) PEO, PEO 750, PEO 2000 DCM1 and PEO DCM 2 Silica.

90

These effects can be confirmed with 29Si Solid State NMR to check the degree of

substitution (ie.T for silanes and Q for bulk) of surface of silica. 29Si Solid State NMR

experiments were done with cross polarization [6].

As a result, the intensity of peaks not only depends on silicon concentration, but

also depends on the contact times which are different between Q1, Q2, Q3, Q4, T1, T2 and

T3 (chapter one, section 1.6.2.1 and section 1.6.2.2). That is why in this section for

comparing reaction yield of different silanes, Q2 to Q4 species are considered not T

species due to differences in hydrogen atoms around T species which depend on type of

silane. However the environments of Q species are only hydroxyl.

Neat silica A300 29Si NMR spectrum shows Q2 to Q4 peaks [7-9]. During silica

surface functionalization reaction with silane, Q2 species change to Q3 and surface Q3

can change to Q4.

As shown in Figure 3. 13 in both vinylsilane and propylsilane the Q2 peak

disappeared, and the ratio of Q4 to Q3 in both silanes increased which proves reaction

occurred between alkoxide in silane and silanol on the surface of silica. Also the ratio in

vinyl-silica is higher than ratio in propyl-silica, which means the number of vinyl groups

which were reacted with silica is higher than number of propyl groups on the surface of

silica. These results were observed in in the earlier TGA results (Figure 3. 10).

The remaining results on silane with different lengths of PEO in Figure 3. 13

show that the number of silane groups attached decreases with increase in length of the

PEO organic tails. The maximum functionalization occurred in PEO-silica where the Q4

peak is quite obvious. In PEO2000 silane DCM1 and DCM 2, Q4 peaks are very broad

and also Q2 peaks did not disappear completely, but the ratio of Q4 to Q3 in DCM 2 is

higher than is the ratio in DCM 1. Also the ratio for Q2 peak in DCM 2 is smaller than

the ratio for this peak in DCM 1. These results illustrate the number of anchoring silane

groups in DCM 2 (which is made by the dropwise adding method) is higher than is the

number of anchoring silane groups in DCM 1.

These results can be used as a simplified model for analysis of the possibility to

synthesise networks with silica as a crosslinker in the absence of water molecules (the

first possible synthesis strategy of a network). The similarity of synthesis of networks

91

with silica crosslinker with functionalized silica is the same method of reaction which

must be applied for both syntheses. However, the difference in network synthesis is that

in the model, only one end is capped with silane (ie. triethoxy silyl propyl urethane-

PEO) as active site for reaction instead of both ends (bis(triethoxy silyl propyl

urethane)-PEG) which are capped in the network precursor.

The probability of synthesis network in dry method with silica as crosslinker is

very low due to following discussion:

• Firstly, during development of a three dimensional structure, viscosity

increases rapidly and the accessibility of silane to the surface of silica

becomes difficult.

• Secondly, when one side of precursor reacts with the surface of silica the

movement of the other silane at the other end of chain is restricted to a

sphere with the reacted silica center and end-to-end distance of the

precursor as a radius. This drops the rate of reaction dramatically.

• Thirdly, the yield of reaction between silica and silane even in a very

small organosilane molecule such as vinyl-silane is very low. The low

yield is seen by 29Si NMR spectrum which shows the existence of silanol

on the surface of silica after completion of the functionalization reaction.

Finally, the TGA and 29Si NMR results show the number of anchored chains on

the surface of silica decreased with increase in length of the polymer chain. This is due

to the number of entanglements and viscosity increase as well as interaction between

organic chains in silane and silica surface.

This means it is almost impossible to synthesise networks only with silica

crosslinker in dry condition (the first possible synthesis strategy of network). For

addressing this limitation, sol-gel reaction is another option where reaction can occur on

the surface of silica as well as between end group silanes through hydrolysis and

condensation reaction (as was discussed in chapter one, section 1.5.2).

92

3.2.3 Synthesis of Network with Sol-gel Reactions (The Second Possible Synthesis

Strategy)

As was discussed in the previous section, the sol-gel reaction can be a good

option for synthesis of novel, chemically crosslinked networks with formation of Si-O-

Si bonds. The novelty and advantage of this synthesis method is the possibility of

controlling crosslink structures which ultimately can control the final network structure

and properties. The other advantage is the existence of active sites for chemical bonding

between polymer chains and the surface of silica as an active filler in composite

networks.

As was discussed in chapter one, section 1.5.2, several parameters such as pH,

water, heat and solvent can control silica formation and silica structures. These

parameters are able to control formation of silsesquioxane structures at the end of

polymer chains such as linear trimer, cyclic trimer and cyclic tetramer silsesquioxane

structures [8, 10].

3.2.3.1 Synthesis of in Situ Silsesquioxane Structures as Crosslinker and Effects

of Silsesquioxane Crosslinker Structures on Network Properties

The networks which are synthesized with sol-gel reactions can be analysed with 29Si Solid State NMR to reveal the nature of the Si-O-Si bonds. The other technique

which can be applied is Differential Scanning Calorimetry (DSC) to examine crystal

structures, crystal transition temperature, and in some cases glass transition temperature

(Tg). It should be noted that the PEG segment of network is the only segment that can be

packed in crystalline regions. The third technique is dynamic mechanical thermal

analysis (DMTA) which can detect changes in amorphous and crystalline structures of

PEG by indicating changes in temperatures and intensity of the α-transition and α’-

transition temperatures.

Polymer chain structures are related to the monomer functionality. TEOS is a

tetrafunctional (f=4) monomer, because each alkoxide with or without hydrolysis is a

functional group. Linear polymerization needs two functional groups in monomer, more

than two functional groups can produce three dimensional structures [11]. This is the

reason that crosslinking agents have at least three functional groups.

93

In bis(triethoxy silyl propyl urethane)-PEG, which is the precursor, a total of 6

functional groups are available at both ends (equation 3.2).

As discussed in chapter one, section 1.5.2, based on reaction conditions and type

of catalyst, different numbers of functional groups react with each other. The number of

reacted groups can change the polymer chain situation from dangling chain (T0) to fully

reacted silane (T3) [8, 10].

OSi N

H

CO

O

O

OO

OC

NH

O

SiO

O

O

n-1

(3.2)

This variety of structures is shown in chapter one, section 1.4.3.1 in equation

1.26 b, and in particular the mesh size can be altered with crosslink structure.

The alteration of the crosslinking structure (the in situ silsesquioxane crosslink)

is an advantage of this method of reaction. If this method is compared with a

conventional method such as free radical polymerization of diacrylate PEG, there are

two major differences. The first one is the number of available functional groups which

in the silane method is six and in the conventional method is three to four. The second

which is the most important advantage is that the sol-gel reaction is controllable and it

can be tailored with reaction conditions. This control of crosslink structure is very

important when a gel must separate swelling agents with different sizes such as proteins

or achieve a controlled release rate of different solutes from a gel.

3.2.3.1.1 Structure analysis by Differential Scanning Calorimetry (DSC)

DSC is a routine and sensitive method to measure transitions of polymers as a

function of temperature through the changes in heat capacity. As the method of network

synthesis in this study produces subtle changes in network structure, it is necessary to

determine if DSC has sufficient sensitivity for characterization of these types of

network.

94

Figure 3. 14. Crosslinked network with dangling chains.

For this determination, dangling chains were systematically added into networks

by adding different percentage of triethoxy silyl propyl urethane-PEO (0%:

PEG2000SWD0, 1%: PEG2000SWD1, 5%: PEG2000SWD5, 10%: PEG2000SWD10,

15%: PEG2000SWD15 and 20%: PEG2000SWD20) during the synthesis of networks

as was described in chapter two, section 2.4.2. The size of triethoxy silyl propyl

urethane-PEO was 2000 Da which is the same length as PEG chains in the network.

This was chosen since when the networks and dangling chains are similar, the

crystalline structures are controlled only by the dangling chains portion. The method of

synthesis was exactly the same for all networks to eliminate all unknown effects. In

Figure 3. 14 the crosslinked network is shown in the amorphous state. All dry networks

were examined by 29Si Solid State NMR, DSC and swelling measurements in water at

equilibrium.

Generally, randomly crosslinked polymer chains cannot pack in large crystalline

domains, due to irregularity in the backbone which is caused by the crosslink branch

points. The other factor that suppresses crystallinity is the decrease in backbone

flexibility because of crosslinking [12] (as mentioned in chapter one, section 1.7.1.2).

However, in PEG, crosslinking occurs only at the ends of chains, so the chain length

between two crosslink junctions (which in PEG is directly related to the molecular

95

weight) may be long enough to pack in crystalline domains. As an example, crosslinked

PEG with molecular mass 400 Da cannot pack in a crystalline domain, but under the

same conditions for crosslinking in PEG with 2000 Da, the chains can crystallize.

However, the degrees of crystallinity with and without crosslinking in PEG with 2000

Da are not the same (which will be examined by DSC later in this chapter).

When a polymer with free ends is packed in a crystalline domain, both ends can

get close more easily during the crystallization process compared to a crosslinked

polymer such as the PEG network. In crosslinked PEG, end of chains are attached

together by crosslinking junctions. During the crystallization process these junctions

need to move closer together due to chain folded model in crystalline regions (as

mentioned in chapter one section 1.7.1.2). However this movement is very difficult in

three dimensional networks, because the junctions have to move in three dimensions

when all PEG chains are attached in random directions around the junctions. This

random chain arrangement develops stress on the PEG chains during crystallization

process due to chain packing and junction movement. These two opposite phenomena

work against each other to hinder the crystallization process. As a result, the size and

structures of crystal cells can change compared to neat PEG 2000 Da without any

crosslinking (as will be explained by DSC runs later in this chapter). Crosslinked PEG

undergoes a strain crystallization process which changes the crystalline size and

structure [13]. This can be observed in a DSC experiment as a shift in the crystal

transition temperature (which, as mentioned in chapter one section 1.7.1.2 is a first order

transition and is the temperature at which the crystalline portion of the polymer changes

to amorphous).

By introducing dangling chains to crosslinked networks the crystal transition

temperature and shape of endothermic peak can change. This dangling chain experiment

can show the sensitivity of DSC measurement in PEG based networks.

The effect of PEO 2000 dangling chain added to silane crosslinked PEG

networks is shown in Figure 3. 15:

96

Figure 3. 15. DSC scans showing the effect of different percentage of PEO2000

dangling chain on the crystal transition in PEG 2000 networks made by a sol-gel

reaction (Step crystallization method with 5°C per minute heat rate).

The DSC results show that as the ratio of dangling chains changes from 0% to

20% (from PEG2000SWD0 to PEG2000SWD20) the peak shift to higher temperature.

This increase in crystal transition temperature indicates an increase in the crystal size (as

discussed in chapter one section 1.7.1.2). This is because the increase in the number of

free chain ends make the crystallization process easier. The results also show the

sensitivity of DSC method in PEG networks since there is an increase in transition

temperature even with addition of 1% dangling chains.

Further information on the networks structures in the crosslinked area were

obtained with 29Si NMR.

97

Figure 3. 16. 29Si Solid State NMR of PEG 2000 networks with different

percentages of PEO 2000 dangling chains.

The results of 29Si NMR illustrate two small peaks in 0% and 1% PEO 2000

dangling chain networks which is for T1 environment of silicon. These T1 silicon

structures can be caused by either chain extension reaction (when two silane groups

react together) or end groups in T2 and T3 structures. All possibilities are shown in

equation 3.3 where only the structure in T1-T1 represents chain extension, and T1-T2 and

T1-T3 are a type of crosslink structure.

(3.3)

If chain extension occurs, the length of PEG chain increases and this can change

the crystal transition temperature to higher temperature, whereas the other crosslinking

structures (T1 as end groups, T2 and T3 species) shift the crystal transition temperature to

lower temperature, as mentioned earlier in this section, due to crystallization under

stress.

98

For almost all percentages of PEO2000 dangling chains in PEG 2000 networks,

peaks in T3 species are very similar, and there are no significant differences in this

region. However, in T2 species, the peaks become broader with increasing PEO2000

dangling chains from -57 to -54 ppm, but from -62 to -60 ppm the bands are the same

shape. It may be the effect of a decrease in concentration of silane with increase in the

PEO 2000 dangling chain species, but the rest of agents are kept constant. The small

shoulder from -57 to -54 ppm in the T2 region is not very large when compared to total

T2 species. At this stage it is difficult to discuss in more detail the types of neighboring

silicon structures. The possible structures for T2 are T1-T2-T1, T1-T2-T2, T1-T2-T3, T2-T2-

T2, T2-T2-T3 and T3-T2-T3 (To these structures cyclic structures must also be added).

Although crystalline structures can change with these structures of T2, the hump from -

57 to -54 ppm as mentioned earlier is very small compared to all T2 that is reasonably

constant in rest of the region of T2.

The spectra show there is no peak at -46 ppm which is for T0 structure with

unreacted chain ends. This means all silane-terminated groups were changed to Si-O-Si.

Overall, the effects of differences in all T1, T2 and T3 structures on the crystalline

structures compared to the effects of dangling chains can be less. If all results in both

0% and 1% PEO2000 dangling chain networks are compared, 29Si NMR results in both

networks are almost identical (Figure 3. 16), however, fractionation DSC results for

both networks show quite remarkable difference in crystal transition temperature (Figure

3. 15).

The other experiment which can illustrate the effects of dangling chains on

crosslinked networks is the swelling measurement in water. Figure 3. 17 shows the

percentage of swelling against percentage of dangling chains. Although the differences

in swelling percentage between the lowest (PEG2000SWD0) and highest

(PEG2000SWD20) are not a large amount, the trend of swelling percentage shows a

continuous increase from 0% to 20% of dangling chains. This is consistent with a

decrease in the density of the network in crosslinked region when the percentage of

dangling chains increases. This causes easier movement in crosslinked regions, when

fewer chains are constrained.

99

Figure 3. 17. Effects of percentage of dangling chain on swelling percentage. (Note

the vertical scale in this diagram does not start from zero).

To determine the unreacted polymer chains, the sol fraction was measured by

immersing the hydrogels in water for several days, then percentage weight lost was

calculated by a gravimetric method and is shown in Figure 3. 18. This graph shows a

very low amount of unreacted polymer chains are in these hydrogels as sol fraction, and

around 99% of polymer chains have attached together during crosslinking process. In

other words, almost all silane groups (T0) during sol-gel reaction changed to one type of

Si-O-Si (T1, T2 and T3). These results confirmed the 29Si NMR results in Figure 3. 16

which show that no silane exist (T0) remains.

100

Figure 3. 18. Percentage of sol fraction in hydrogels with different amount of

dangling chain.

3.2.3.1.2 Effects of Amount of Acidic Water on the Sol-gel Reaction for Network

Formation

In chapter one, section 1.5.2 it was noted that sol-gel reactions in acid-catalyzed

hydrolysis reactions are first-order in [H2O] [8]. So the hydrolysis reaction can be

promoted with an increase in water concentration. The sol-gel reaction also depends on

catalyst concentration which is first order as well [8]. However, after a certain level of

water addition the gelation time can increase rapidly, because of a decreasing

concentration of Si ([Si]) and the structure as well as the condensation rate can change.

Silsesquioxane structures depend on the competition between hydrolysis and

condensation reaction rate. As mentioned in equation 1.43 in chapter one, the rate of the

condensation reaction is first-order in proton [H+] and second-order in silanol

concentration. In this section, the effect of these concentrations on network structures

will be examined by changing the amount of acidic water added. The goal is to see the

way in which the network properties such as crosslink structures, crystalline structures

and swelling at equilibrium can be controlled.

101

The reaction conditions, as mentioned in chapter two section 2.4.2.1, for all

samples were the same, only different amount of acidic water (0.1M HCl) were added to

each sample (50 μl: PEG2000SW1 , 100 μl: PEG2000SW2, 150 μl: PEG2000SW3 and

200 μl: PEG2000SW4).

The four samples that were synthesized are shown in Figure 3. 19 in which

changes in the transparency of the samples are obvious. These transparency changes are

due to crystalline effects where smaller crystalline regions cannot scatter visible light,

but when the crystallite size gets bigger than specific dimension, visible light started to

be scattered. As a result, the samples get opaque with increasing the size of these

crystallites. This phenomenon was further studied by DSC in Figure 3. 20.

Figure 3. 19. Photos of networks at around 22 °C (room temperature) which were

made by sol-gel reaction with different amounts of 0.1M HCl. Note the increasing

opacity with amount of acidic water used in the synthesis.

In Figure 3. 20 step crystallization DSC results are shown. The crystal transition

temperatures increase with rising amount of 0.1M HCl. In these results the difference is

very obvious between samples PEG2000SW1 and PEG2000SW2. This is because

[water] increases (the reaction is first-order in water concentration) and the solution pH

is decreased with each addition of extra water. As mentioned in chapter one, section

1.5.2, in situ silsesquioxane structure can be altered by rate of hydrolysis and

condensation reaction. The combination of these two major changes causes nearly 7 °C

shift in transition temperature.

102

Figure 3. 20. Fractionation DSC results of samples formed with an increasing

amount of water with 0.1M HCl in networks with PEG2000.

The rest of the results illustrate a smaller increase in the crystal transition

temperatures, when the amounts of acidic water increase. This follows from the fact that

Mc (molecular weight between two crosslinking junctions) in all the networks is exactly

same, but the only parameter that can control these crystal transition temperatures is

structure of crosslink.

Mechanical Thermal Analysis (DMTA) technique. The changes in the tan δ

curve both in α-transition and α’-transition region arise from second-order transitions

which are different from those obtained with the step crystallization method in DSC.

However the large change in storage modulus (E’) results can be considered to arise

from the first order (melting) transition, the same as DSC results (this was discussed in

chapter one, section 1.8).

Figure 3. 21 shows tan δ and E’ against temperature, and in E’ only the crystal

transition temperature area was shown. The DMTA test was done in compression mode

103

of deformation. The results show that tan δ in PEG2000SW1 has the lowest glass

transition temperature (Tg). Note that in this chapter the maximum in tan δ is consider as

Tg but it may also be defined as the onset point of rapid change in tan δ. By increasing

the amount of acidic water from sample PEG2000SW1 to sample PEG2000SW4, the

maximum of tan δ shifts to higher temperature. Also the tan δ results in samples

PEG2000SW3 and PEG2000SW4 are very close together.

Figure 3. 21. Dynamic Mechanical Thermal Analysis (DMTA) plots of tan δ and E’

against temperature with change of amount of 0.1M HCl in networks with

PEG2000.

The α’-transition in dry PEG2000SW1 appears at the lowest temperature and is

rather broad and ill-defined. The α’-transition shifts to higher temperature with an

increase in the amount of the acidic water. In PEG2000SW2, two humps are obvious

where the first is broader and smaller than the other one which is at a higher temperature

and sharper. These two humps represent two different transitions. This result is

104

consistent with the DSC results in Figure 3. 20, where this sample shows an

endothermic peak at 21.5oC. Storage modulus (E’) in this sample which is broad over a

large temperature range is lower compared to other networks. This trend was also seen

in the earlier DSC data. The α’-transition peaks in PEG2000SW3 and PEG2000SW4 are

sharper and shift to higher temperatures, however, the peaks are very close together.

The storage modulus in samples from PEG2000SW1 to PEG2000SW4 has the

same trend in tan δ (both Tg and α’-transition) and DSC that shows that the crystal

transition temperatures increase. It must be noted that the measurement of E’ is

extremely sensitive to sample preparation and mode of deformation.

The results from DSC (the crystal transition temperature) and DMTA (Tg, α’-

transition and modulus change versus temperature) are reasonably matched together.

They show crystallinity increases with increased amount of 0.1M HCl during synthesis.

The DSC result is very obvious, but the DMTA results need to be elaborated. The α-

transition which indicates the glass transition temperature depends on degree of

crosslinking, crystallinity, fillers and additives (as mentioned in chapter one section 1.8)

[14, 15]. The definition of Tg (α-transition) is the temperature that several repeating

units of backbone of polymer chain (around 20 to 25 units) start vibration and

movement. Anything such as crystalline regions, crosslinks or filler which can hinder

this movement causes shift in Tg to higher temperature. (This was explained in chapter

one section 1.7.1.1 and will be discussed in the next chapter).

In the PEG network the crystalline blocks may act as physical crosslinks. In

Figure 3. 21 the results can change when both of these variables (crystallinity and

crosslinking) are changing due to change in crosslinking structures. However,

crystallinity has a higher effect on the glass transition temperature compared to

crosslinking [15].

Increase of crystallinity leads to a decrease in the amorphous fraction which

shifts Tg to higher temperature [12, 16]. The glass transition temperature in these types

of networks is controlled by amorphous chains which are confined between crystalline

regions and between crosslinks [14, 15]. In this method of network production, when the

105

crosslink structure (all of the structures T1, T2 and T3) becomes dense, the fraction of

crystallinity decreases (as explained by 29Si Solid State NMR).

The results which were obtained by DSC and DMTA techniques must be

compared with 29Si NMR to show the effects of crosslink structures on crystallinity, and

ultimately illustrate the effects of conditions of reaction on network structures. Figure 3.

22 shows changes of Si-O-Si species with change in the conditions of reaction. The

NMR spectra in networks from PEG2000SW1 to PEG2000SW4 show T1 at chemical

shifts of -50 ppm, T2 from -63 to -53 ppm and T3 from -73 to -64 ppm.

Figure 3. 22. 29Si Solid State NMR spectra in networks that were synthesized with

different amount of 0.1M HCl.

In PEG2000SW1, T3 structures are very obvious that are the highest

concentration of T species. These T3 species make very dense three-dimensional

networks, as a result, polymer chains during crystallization process can experience very

high strain, because ends of each chain in these networks were chemically attached

together through the Si-O-Si linkage. During the crystallization process amorphous

chains which can freely move due to random and less ordered structures must be packed

in a very high order crystalline domain with very restricted movement. Also during this

crystallization and packing process, the polymer chain dimensions are shrunk. As

106

mentioned in the previous section, this shrinkage in crosslinked networks leads to

displacement of crosslink region in a direction such that both end of polymer chain get

closer together. When the crosslink structure has higher density T3 structures with the

higher number of attached polymer chains in each crosslinking particle, dislocation of

crosslink cannot easily occur, and it develops a strain on polymer chains during packing.

Formation of crystalline structures under strain is rather difficult and causes crystalline

blocks of small size to be formed which lowers the crystal transition temperature. This

mechanism, when the number of silicon atom per crosslinking particle increases, can

hinder crystallization process easier compared to when there is a lower number of

silicon atoms per particle However in T2 crosslink structures, three dimensional

networks in most cases can have lower density compared to T3 structures. In these

structures (T2 structures) the number of attached polymer chains in each individual

crosslink area is lower, which causes easier movement during crystallization process

compared to all T3 species. Thus it is difficult to have pure T2 structures or T3 structures.

For particle formation it is necessary that T3 structures are formed since it is impossible

to produce particles with pure T2 structures. However, T2 structures are sufficient to

produce three-dimensional networks (Figure 3. 23). When T2 structures are formed more

than T3 structures, the neighboring groups around T3 structures are more T2 or in some

cases T1 (as end groups). These neighboring changes causes shift in T3 structures peak

in 29Si Solid State NMR [8, 17].

The other T structures are T1 that produce chain extension. This structure can

promote crystallization due to chain extension and the increased length of polymer

chain. At the end, structures of the in situ silsesquioxane in configurations T1, T2 and T3

can be formed (Figure 3. 23 a and 3. 23 b).

107

Figure 3. 23. T1, T2 and T3 structures in crosslink area and particles with attached

polymer chains. Oxygen, silicon and hydroxyl are not shown.

Figure 3. 22 shows 29Si Solid State NMR spectra for PEG2000SW1,

PEG2000SW2, PEG2000SW3 and PEG2000SW4. By increasing the amount 0.1M HCl,

T3 (-73 to -64 ppm) decreases and shifts. The results show the number of T3 structures

which are from high density Si-O-Si particles decreases and shifts to the other T3

structures and T2 structures that are of lower density. The T3 structures in PEG2000SW1

shows maximum peak at -68 ppm, in PEG2000SW2 two overlapped peaks appear (-68

and -66 ppm) and in PEG2000SW3 and PEG2000SW4 samples the maximum in peak

appear at -66 ppm. This shift in 29Si NMR from around -68 to -66ppm in T3 structures

shows sensitivity of these structures at crosslink points to amount of acidic water (0.1M

108

HCl). In PEG2000SW2 sample the T3 structure appears to have features of both the In

PEG2000SW1 and In PEG2000SW3 samples resulting in overlapping peaks between -

68 and -66ppm.

In T2 structures (-63 to -53 ppm), peaks apparently become broader with

increased amount of water. This is because a small peak appears around -55 ppm that

starts as a shoulder of the main peak. With an increase in the amount of 0.1M HCl added

during synthesis, the shoulder gets bigger and changes to a partially resolved peak in

networks synthesized with 150 and 200 μl 0.1M HCl. These results illustrate T2

structural variations (T2 species which, as mentioned earlier in this section, are related to

the neighboring silicon atoms structures that can be T1, T2 and T3 or T2 cyclic structures

as shown in Figure 3. 23 a) when the amount of 0.1M HCl is changed. This change

when compared to DSC and DMTA results may show the structure changes from high

density T2 (where the neighboring silicon atoms must mainly be T3) to lower density T2

structures with less T3 and more T2 neighboring silicon atoms. This idea can be clarified

better by considering 29Si NMR results (Figure 3. 22) for the T3 and T2 peaks together.

When T3 peak decreases and shifts to other T3 structures, the shoulder at -55ppm (due to

T2 structures) increases with the amount of 0.1M HCl added. There are two possibilities

for formation of T1 structures which appear either during chain extension (only two

silane react together and make Si-O-Si) or at the end of T2 and T3 structures as end

groups. In 29Si Solid State NMR a peak around -51 to -49 ppm shows T1 structures

which are believed to be at the edge of T2 and T3 structures as end groups (Figure 3. 23 a

and b).

To determine if structures were formed with silane-terminated dangling chains, 29Si Solid State NMR may also be used (Figure 3. 24). When a silane group does not

react with other silane groups during sol-gel reaction, it stays as T0 structure as a

dangling chain (as mentioned in section 3.2.3.1.1) or unreacted (dead) chain. This T0

structure can be detected by 29Si Solid State NMR by comparison with the parent silane.

In bis(triethoxy silyl propyl urethane)-PEG precursor, T0 is the unreacted silicon

structure which in 29Si NMR gives a sharp band around -46 ppm (Figure 3. 6). This is

also shown along with the network spectra in Figure 3. 24. It is seen that there is no

significant T0 peak in networks after sol-gel reaction. This means all silane groups were

109

reacted and changed to Si-O-Si linkage groups which can be either T1, T2 or T3 silicon

structures.


different amount of acidic water of pH 1 and bis(triethoxy silyl propyl urethane)

PEG.

The other measurement that shows the differences in the network structures is

the water swelling at equilibrium. As mentioned in chapter 1, section 1.3.3, gels keep

swelling until chemical potential of swelling agent inside and outside of gels become

equal which is the equilibrium point for a specific swelling agent. At equilibrium the

osmotic pressures inside and outside (in solution) of the gels are equal. The amount of

swelling at equilibrium can be controlled by the crosslink structures. This is because

when the crosslink structure becomes high density (such as higher in T3) crosslink

cannot move easily compared to low density of crosslink. (This is analogous to

crystalline structures which need displacement). As a result, the networks with high T3

(high density crosslink structures) develop higher osmotic pressure inside the networks

at a lower extent of swelling, compared to networks with lower density of crosslink

structures which have mostly T2 structures.

110

0

50

100

150

200

250

300

350

PEG2000SW1 PEG2000SW2 PEG2000SW3 PEG2000SW4

% o

f Sw

ellin

g

Figure 3. 25. Swelling of hydrogels (synthesized with different amounts of 0.1M

HCl) when immersed in pure water.

Based on rubber elasticity theory this deformation in networks with T3 crosslink

structures causes a higher recovery force to return the swollen networks to the un-

stretched condition (ie. The condition before swelling). As shown in Figure 3. 26, the

polymer chain in a crosslinked network acts as an entropic spring; during deformation,

the entropy is changed due to the reduced number of available conformations so the

chain can develop a restoring force which tries to return the polymer network to an

equilibrium state)

Figure 3. 26. Changing the number of conformations of a polymer chain during

stretching.

This explanation is obvious in Figure 3. 25 which shows that the lowest

percentage of water absorption occurs in PEG2000SW1 hydrogel. This hydrogel shows

the highest concentration of T3 species compared to the other three hydrogels (Figure 3.

111

22). With increased number of T2 structures, the percentage of water at equilibrium

swelling increased (PEG2000SW2, PEG2000SW3 and PEG2000SW4).

This trend in equilibrium swelling results shown in Figure 3. 25 are further

evidence of the effect of the amount of acidic water during synthesis on these types of

network structure. Significantly, in this method of synthesis (based on the level of acidic

water), the structures of crosslink and ultimately, mesh size and crystallinity in networks

can be controlled whereas in conventional method of synthesis such as acrylate-PEG

based networks this alteration in mesh size and crystallinity is more difficult.

As shown in Table 3. 1, mesh sizes and molecular weights between two

crosslink junctions (Mc) have remarkable differences between theoretical (I) and

calculated (II) values (equation 3.4) [18]. The Mc and mesh size are calculated based on

Flory-Rehner (Peppas-Merrill) theory [19] and model.

( ) 22, 2, 2,

1

2,1 32,

ln 11 2

2

s s s

scs

VM M

ν ν ν χν

νν

⎡ ⎤− + +⎣ ⎦= −

⎡ ⎤−⎢ ⎥

⎣ ⎦

(3.4)

where 2,sν is volume fraction of polymer in swollen gel, ν is the specific volume

fraction of the polymer, χ is polymer-solvent interaction parameter, V1 is the molar

volume of swelling agent and M is molecular weight of polymer chains before

crosslinking. The mesh size (ξ) is calculated from equation 1.4 at equilibrium swelling.

Table 3. 1. Molecular weight between two crosslink junctions I: theoretical and II:

calculated. Mesh size is based on Mc values in hydrogels (synthesized with different

amounts of 0.1M HCl) when immersed in pure water

I II

Mc(theor)

(g/mol) Mesh Size

(Å) Calculated Mc (g/mol)

Mesh Size (Å)

PEG2000SW1 2000 39.8 297 15.4 PEG2000SW2 2000 43.1 389 18.6 PEG2000SW3 2000 44.0 439 20.2 PEG2000SW4 2000 44.0 442 20.4

112

There are several possible explanations for Mc differences between calculated

and theoretical values. Based on Flory- Rehner theory Mc can be calculated from rubber

elasticity theory. In rubber elasticity theory the crosslink structure is homogenous, and

related to the entropy change arising from deformation of network [20]. However, in

situ silsesquioxane PEG networks have non-homogenous crosslink structure due to

chain-end crosslinking reaction (silane part of chains) which causes deviation in the

calculation. The other possibility, according to Hennink and colleagues [21, 22], is an

entanglement effect on the swollen network which gives an intramolecular crosslinks

compared to intermolecular (chemical) crosslinks. Another possibility is that the water

does not totally destroy the structure of the crystalline domains so there are virtual

crosslinks in the system. Consequently, intramolecular crosslinks reduce the calculated

Mc values to less than the theoretical value from the PEG chain length [20]. Moreover,

bis(triethoxy silyl propyl urethane)-PEG precursor has a functionality of 6 compared to

a functionality of 4 used in the Flory- Rehner theory. Hennink [21] mentioned the

crosslink structures cause difference in Mc between calculated and theoretical methods,

because the percentage of swelling depends on the crosslink structures as described in

this section (Figure 3. 25). The other assumption in the Flory-Rehner model is

independency of χ from 2,sν , whereas, the literature [20-22] mention the polymer-

solvent interaction parameter is a function of volume fraction of polymer.

In Figure 3. 27 is shown the sol fraction percentage in PEG2000SW1,

PEG2000SW2, PEG2000SW3 and PEG2000SW4 hydrogels. The low values show the

hydrogels are very stable in water for several days at 40 °C and it is concluded that

almost all of the bis(triethoxy silyl propyl urethane)-PEG precursor was reacted and

changed to linkage (Si-O-Si) of structure T1 to T3.

In the rest of this chapter the effect of different parameters such as concentration

of HCl will be investigated.

113

00.20.40.60.8

11.21.41.61.8


% o

f Sol

Fra

ctio

n

Figure 3. 27. Percentage of sol fraction in hydrogels synthesized with different

amounts of acidic water (0.1M HCl).

3.2.3.1.3 Effects of Different Concentration of Hydrochloric Acid Solution on Sol-

gel Reaction in the PEG 2000 Network

In this section the effect of changing HCl solution concentration on the structures

of crosslinks will be studied. As mentioned in chapter one, section 1.5.2.1, the

concentration of acid as a catalyst has very critical effects on the Si-O-Si synthesis

which can change structures in both Q and T types of silica [8, 10]. The pH changes can

affect both hydrolysis and condensation reactions. The acid-catalyzed hydrolysis and

condensation reactions are first-order in acid concentration. To eliminate the effects of

volume change, in these experiments only concentration of added HCl was changed (ie

the volumes of hydrochloric acid solution were kept constant). All other conditions such

as, temperature and initial water and methanol volume were exactly similar for all

samples.


samples were the same, only different concentration of HCl were added to each sample

(0.001M HCl: PEG2000SH1, 0.01M HCl: PEG2000SH2, 0.05M HCl: PEG2000SH3

and 0.2M HCl: PEG2000SH4).

114

For all the samples, DSC with step crystallization method was applied to

determine the crystal transition temperatures against the acid concentration values used

for synthesis. In Figure 3. 28 the results are presented and the crystal transition

temperatures increase with rising HCl concentration with only the 0.001 M the sample

not following this trend by showing the highest transition temperature. One possible

explanation can be the existence of dangling chains (which was extensively discussed in

section 3.2.3.1.1) and the other reason can be chain extension through the condensation

reaction. To examine this idea, 29Si Solid State NMR was applied to check the existence

of T0 and T1 structures.

Figure 3. 28. DSC results with change in HCl concentrations from 0.001 to 0.2 M in

networks with PEG2000.

The results at Figure 3. 29 show that relative intensity in T3 (-73 to -64 ppm)

structures in sample PEG2000SH4 are higher than other three networks which were

synthesized by a lower concentration of HCl. However, both the literature [8, 10] and

115

the DSC results show the NMR relative intensity of T3 structures in network with 0.2 M

HCl must be lower than other three networks. However, T2 structures illustrate very

good agreement with both literature and the DSC results in all samples which were

synthesized (0.01, 0.05 and 0.2 M HCl). Results in DSC and NMR in network 0.001 M

HCl (PEG2000SH1) are completely different compared to the other three networks.


different HCl concentration from 0.001M (PEG2000SH1) to 0.2 M HCl

(PEG2000SH4).

As shown earlier in Figure 3. 15, the crystal transition temperature can be

controlled by the number of dangling chains (from around 1%) which exist in networks

and crosslinked polymers. In Figure 3. 29, in PEG2000SH1, two peaks around -51 to -

49 ppm which show T1 structures and -46 ppm that shows T0 structure are obvious. The

T0 structure implies the existence of dangling chains in this network which explains the

observed shift in the crystal transition temperature to higher temperature. (This was

confirmed earlier by the dangling chains experiment in section 3.2.3.1.1). However, it is

hard to say the whether the presence of T1 structures indicates chain extension or not.

The magnitudes of the peaks in T2 and T3 in the 29Si NMR spectrum for

PEG2000SH1 sample indicate that the number of silicon species with T3 structures is

116

higher than T2 structures. Consequently, the final properties and structures in this

network as supported by the DSC result are mainly controlled by T0 and possibly by T1

structures rather than T3 or T2. This result illustrates that detailed interpretation of T2

and T3 structures need more information about all neighboring groups, because these

cause three dimensional changes in networks. As an example, T2 structure in T1–T2–T1

produces a lower density crosslink network than a T2 structure in T3-T2-T3. These

differences are potentially detectable with 29Si NMR (especially in liquid NMR) [8],

however, this needs a higher concentration of silicon atoms in the sample. In this study,

further peak interpretation was not possible due to the very low concentration of silicon

atoms. Consequently this study has mainly been done on Q structures rather than T

structures. To address this limitation, different methods of experiment have been

employed such as step crystallization DSC and equilibrium swelling measurements in

water.

If all the results in DSC and 29Si Solid State NMR are compared, it is obvious

that the crystallinity can be altered with T structures and distributions of T structures.

This does not mean all T structures have the same influence on the sample structure.

Based on these results, T3 structures do not have a great effect on crystallinity and

network structures compared to T2 and T1 structures. As mentioned in section 3.2.3.1.2

in T2 region of the NMR, those structures which are associated with the peak from -57

to -53 ppm are more indicative of the network structures. Even though this peak cannot

be unambiguously assigned, there are systematic changes in both swelling

measurements and DSC that accompany it, consistent with changes in network structure.

However the remaining T2 region (-63 to -57 ppm) in all networks are very similar and

indicate less effect on crosslinking structures. (This idea needs to be tested by different

techniques such as 29Si Liquid and Solid State NMR and MALDI-TOF-MS in different

types of precursors). This idea can be supported by results of DSC, DMTA and 29Si

Solid State NMR in Figure 3. 20, Figure 3. 21, Figure 3. 22 and Figure 3. 23 in previous

section (section 3.2.3.1.2) and the results of DSC and 29Si Solid State NMR in Figure 3.

28 and Figure 3. 29. In the T2 region, the 29Si NMR peaks from -63 to -60 ppm are very

similar in all the network samples, whereas the networks undergo major changes in

structure, when peaks from -57 to -53 ppm show changes. This region of the T2 peak

117

may be associated with low density crosslink structures where the neighboring groups

are T2 or T1 species rather than be very high density T3 species.

In Figure 3. 29 in PEG2000SH4 which was made with 0.2 M [HCl], although the

peak in T3 region is very intense and sharp, the DSC results in this network show a

higher crystal transition temperature which shows the trend of the transition temperature

which shift to higher temperature when amount of acidic water (previous section) or

concentration of [HCl] increase. In this network, the T2 structures in 29Si NMR region

from -57 to -53 ppm are very weak and appear as a weak shoulder. This result shows the

region from -57 to -53 ppm is more useful in characterizing the network and network

structures compared to the peak from -73 to -64 ppm that arise from T3 structures.

The other possible explanation, as mentioned in chapter 1, section 1.5.2.1.6, is

the rate of condensation dependency on pH of solution. Basically, in a normal sol-gel

reaction in TEOS both the hydrolysis and condensation show a minimum around pH 7,

however, in a sol-gel reaction with organo-silanes the condensation rate undergoes a

minimum at lower pH (acidic solition). In these types of silane the hydrolysis shows a

minimum around pH 7. The reason that condensation in an organo-silane takes place at

lower pH is effect of organic tail that is generally an electron donor group and changes

the charge on silicon atom to being partially negative. The minimum condensation

reaction rate depends on the alkyl group. This is another factor that needs to be taken

into account that can change the in situ silsesquioxane structures. However, the rate of

sol-gel reaction is only controlled by the part of reaction which has the lowest rate.

To check the network structure, swelling measurements in water have been done

and show that the DSC results are very sensitive to crosslink structures and match with

swelling measurement results. Figure 3. 30 shows the percentage swelling in water of

networks versus concentration of hydrochloric acid used in synthesis. In three samples,

PEG2000SH2, PEG2000SH3 and PEG2000SH4, the percentage swelling in water

increases systematically.

The interesting result is for PEG2000SH1 hydrogel which has a slightly higher

percentage of water swelling compared to PEG2000SH2. This is because when pH is

around 7 the rate of hydrolysis is very low [8, 10, 23] and the sol-gel reaction needs

118

longer time for hydrolysis. To minimize possible side reactions all reaction conditions

including time and temperature were kept constant for all four samples. If this result is

compared to swelling results in Figure 3. 17, it is possible that the PEG2000SH1

hydrogel which was synthesized with 0.001 M HCl shows effects of either dangling or

unreacted chains. In hydrogels synthesized with dangling chains, the swelling

percentage increases when dangling chains percentage increases (Figure 3. 17). The

result of 29Si NMR in Figure 3. 29 shows PEG2000SH1 hydrogel has dangling chains,

however, PEG2000SH2 does not have any T0 structure. This suggests that the existence

of these dangling chains caused increase percentage swelling due to decreased bonding

between crosslink junctions. The results in Figure 3. 30 also show higher percentage

swelling in sample PEG2000SH4 compared to PEG2000SH3 which correlates with their

respective crystal transition temperatures. Also the network behaviour has less

sensitivity to T3 structures (Figure 3. 29), but is sensitive to some part of T2 structures (-

57 to -53 ppm).

These results show that when acid concentration increases during synthesis, both

the crystal transition temperature shifts to higher temperature and the percentage of

swelling in water increases. The other outcome in this part of study is related to 29Si

solid state NMR identification of network sensitivity to T1, T2 and T3 structures. The

NMR results show swelling and crystallinity of networks are more sensitive to T1 and

some part of T2 compared to T3.

In PEG2000SH1 sample, based on 29Si NMR result, the reaction is not complete

and unreacted chains are seen. As mentioned in chapter one, section 1.5.2.1.2, the rate of

hydrolysis reaction around pH 7 is very slow, however the rate of the condensation

reaction in this region of pH is very fast due to the effect of alkyl groups on the

condensation reaction rate. In other words, the T0 structure in Figure 3. 29 can disappear

when the reaction completely takes place in wet conditions.

119

0

50

100

150

200

250

300

PEG2000SH1 PEG2000SH2 PEG2000SH3 PEG2000SH4

% o

f Sw

ellin

g

Figure 3. 30. Percentage swelling in water of hydrogels which were synthesized

with 0.001, 0.01, 0.05 and 0.2 M HCl (PEG2000SH1, 2, 3 and 4). Average error

bars are considered from section 3.2.3.1.2, Figure 3. 25.

As a result, changes to reaction time may change both swelling percentage and

the crystal transition temperature (Figure 3. 28 and Figure 3. 30).

The sol fraction results in Figure 3. 31 reflect the structural stability as well as

percentage of unreacted materials during sol-gel reaction. PEG2000SH1 hydrogel has a

high sol fraction percentage. This result suggests that the T0 structure belongs to both

dangling chains and dead chains. Dangling chain cannot be washed away with water as

shown in Figure 3. 18 in which hydrogels with dangling chains were synthesized. In

dangling chains one side of the chains chemically attach to other polymer chains in the

network, whereas dead chains stay in the network as an impurity and make no effective

contribution to the network properties. The dead polymer chain can easily be washed

away. When the results in Figure 3. 27 and Figure 3. 31 are compared, it is seen that

networks synthesized with different amount of 0.1M HCl have higher stability structures

120

compared to networks in Figure 3. 31. This may be caused by the rate of hydrolysis

during sol-gel reaction (hydrogel synthesis) which depends on pH of solution.

0

1

2

3

4

5

6

7

8

9


% o

f Sol

Fra

ctio

n

Figure 3. 31. Percentage of sol fraction in hydrogels which were synthesized with

0.001, 0.01, 0.05 and 0.2 M HCl (PEG2000SH1, 2, 3 and 4).

In thermal properties of PEG 2000 networks, the difference between the crystal

transition temperatures compared to PEG 2000 as received (ie not crosslinked and not

functionalized, being only hydroxyl-terminated) are significant.

121

Figure 3. 32. Changes in the crystal transition temperature of PEG 2000 and its

crosslinked networks prepared at different [HCl].

As the DSC traces in Figure 3. 32 demonstrate the crystal transition temperature

shifts to lower temperature as the crosslink structures become tighter due to change in

either amount of acidic water (0.1M HCl) or acid concentration used in their

preparation. This shift can be around 32 °C in PEG 2000 for which the molecular weight

between two junctions is sufficient long to be packed in crystalline region, but

crosslinking can still hinder crystallization in such a long chain (as discussed earlier in

section 3.2.3.1.1).


gel Reaction in the PEG 400 Networks

Polymer chain length between two crosslink junctions is another factor that

affects the final properties of networks such as ultimate swelling. To study this effect,

PEG 400 was selected to prepare a very short chain length network precursor. The

122

bis(triethoxy silyl propyl urethane)-PEG 400 precursor (equation 3.2) was then used to

synthesize crosslinking networks by the sol-gel reaction method.

The bis(triethoxy silyl propyl urethane)-PEG 400 precursor has different

properties compared to bis(triethoxy silyl propyl urethane)-PEG 2000, arising from a

decline in solubility of bis(triethoxy silyl propyl urethane)-PEG 400 in water due to a

greater effect of silane end groups on the lower molar mass PEG 400.

Figure 3. 33. DSC results in PEG 400 and bis(triethoxy silyl propyl urethane)-PEG

400 precursor. a) Heating rate 10 °C per min. b) Heating rate 20 °C per min.

Bis(triethoxy silyl propyl urethane)-PEG 400 shows different thermal properties

in DSC experiments compared to the parent PEG 400 which is shown in Figure 3. 33 a

and b. The results show the bis(triethoxy silyl propyl urethane)-PEG 400 polymer

cannot undergo crystallization compared to pure PEG 400 which clearly can crystallize.

For verification of these results, the experiments were run at two different cooling and

heating rates. In Figure 3. 33 a, the rate of cooling was 5 °C per min. and heating was

10 °C per min. and for Figure 3. 33 b the cooling and heating rates were 10 and 20 °C

per min, respectively. Both experiments show crystallization was totally suppressed by

the addition of silane to PEG 400.

123

The reaction conditions in crosslinked PEG 400 synthesis, as mentioned in

chapter two section 2.4.2.1, for all samples were the same, only different concentration

of HCl were added to each sample (0.001M HCl: PEG400SH1, 0.01M HCl:

PEG400SH2, 0.05M HCl: PEG400SH3 and 0.2M HCl: PEG400SH4).

The main issue in these syntheses was phase separation between water and

polymer. Neat PEG with different chain length is water soluble at room temperature

(with hydrogen bonding being the mechanism of solubility). In PEG 400 the solubility

drops drastically after changing to bis(triethoxy silyl propyl urethane)-PEG. This is

because of the effect of silane groups which are not highly water soluble. However, in

bis(triethoxy silyl propyl urethane)-PEG 2000, because the polyether has sufficient

chain length, water solubility does not decrease significantly. As mentioned in chapter

one, section 1.5.2, water solubility is one of the most important parameters that can

control silsesquioxane structures.

In situ silsesquioxane PEG 400 networks do not show any crystal transition

temperature, because the chains between two crosslink junctions are too short to be

packed in a crystalline region. The resulting structure is fully amorphous and the glass

transition temperature is detectable with DSC, even though the glass transition

temperature in networks from PEG 2000 (in situ silsesquioxane) cannot be measured

with DSC and it was necessary to measure it with DMTA (Figure 3. 21).

From Figure 3. 34 the glass transition temperature of PEG 400 networks

(PEG400SH1, PEG400SH2, PEG400SH3 and PEG400SH4) are found to be -8.06, -

6.56, -8.07 and -10.08 °C, respectively. The DSC results do not show any trend with

different acid concentrations. If in situ silsesquioxane PEG 400 networks followed the

same trend as PEG 2000 networks, Tg should shift to lower temperature when

synthesized with increased acid concentrations due to a decrease in the effective

crosslink density when higher concentration of acid is used.

124

Figure 3. 34. DSC results for in situ silsesquioxane PEG 400 networks synthesized

with HCl acid concentration from 0.001 to 0.2 M (PEG400SH1, 2, 3 and 4. The

heating rate was 10 °C per min.).

In Figure 3. 35, 29Si solid state NMR of in situ silsesquioxane PEG 400 networks

show the effect of concentration on the network structures. The results do not follow any

trend and the interesting result appears in PEG400SH1 samples in which 0.001 M HCl

was used as catalyst. The T0 structure was not observed in this sample due to the longer

time of synthesis. This result confirms that around pH 7 the rate of hydrolysis reaction is

very slow and longer reaction times need to be considered.

125

Figure 3. 35. 29Si Solid State NMR spectra in crosslinked PEG 400 networks that

were synthesized with different acid concentration (from 0.001 to 0.2 M HCl).

Figure 3. 36 shows percentage of swelling of crosslinked PEG 400 in water at

equilibrium. These results also do not show any relation between concentrations of

hydrochloric acid and percentage of swelling.

As discussed earlier, the bis(triethoxy silyl propyl urethane)-PEG 400 precursor

was not soluble in water. This phase separation changes the amount of water and

concentration of hydrochloric acid in polymer solution phase. This transforms a bulk

reaction to an interfacial reaction (between water and polymer solution interface) which

can cause non-uniformity in network structure. The hydrolysis and condensation

reactions follow first-order kinetics in concentrations of both acid and water. Both rate

and mechanism of reaction change with the amount of water, which was explained in

chapter one, section 1.5.2. The silane groups near the surface where contact with water

is made, undergo faster hydrolysis and condensation reactions to make Si-O-Si linkage

bonds through the water-producing condensation mechanism. In contrast, the bulk

reaction takes place through a diffusion-controlled mechanism that can lead to alcohol-

producing condensation.

126

0

10

20

30

40

50

60


% o

f Sw

ellin

g

Figure 3. 36. Percentage of swelling in crosslinked PEG 400 networks that were

synthesized with different acid concentration (from 0.001 to 0.2 M HCl).

This difference is very obvious when the swelling results in Figure 3. 36 are

compared to swelling results in hydrogels from PEG 2000. This shows swelling at

equilibrium decreases with shortening PEG chain backbone length, owing to reaching a

fully stretched chain which causes higher elastic forces inside the network. This elastic

force increases the internal osmotic pressure rapidly and ultimately balances the

chemical potential inside and outside the swollen hydrogels at a lower amount of

absorbed water (as discussed in chapter one, section 1.3.3.

Figure 3. 37 shows the sol fraction result which confirms the reaction occurred

completely and very few chains were washed away. These results can be confirmed by 29Si NMR that shows no band at -46 ppm and thus no T0 structure in these networks

(Figure 3. 35). The 29Si NMR result show, although acidic water with different

concentration cannot be thoroughly mixed with PEG 400 precursor, there is no T0

structure and the reaction occurred completely.

Both percentage of sol fraction (Figure 3. 37) and T0 structure in 29Si NMR

results (Figure 3. 35) in PEG400SH1 confirm that around pH 7, sol-gel reaction needs

127

longer time for reaction. In contrast, in PEG2000SH1 unreacted silane groups were

observed.

0

0.1

0.2

0.3

0.4

0.5

0.6


% o

f Sol

Fra

ctio

n

Figure 3. 37. Percentage of sol fraction in crosslinked PEG 400 networks that were

synthesized with different acid concentration (from 0.001 to 0.2 M HCl).

Phase separation needs to be examined with different experimental techniques

such as dynamic light scattering to detect micelle formation and dimension. The other

factor that needs to be considered is viscosity [8]. Viscosity changes in low molecular

weight precursor become more effective on the structures compared to higher molecular

weight. This is because the number of active groups (silanol and alkoxide) per volume

in lower molecular weight reagent is higher than in a high molecular weight precursor.

During condensation reactions, the viscosity in lower molecular weight precursor

increases faster due to higher number of active groups which can make covalent

crosslink bonds, and remaining active groups face difficulty in reacting with other active

sites, ie. either silanol groups or silica oligomers. These effects can increase when the

precursor gets shorter, because the radius (contour length or the maximum distance the

chains end can move for reaction) also gets shorter. These distances are controlled by

128

polymer random coil theory which says it is unlikely that polymer chains experience a

fully stretched conformation under equilibrium conditions [12, 24, 25].

Figure 3. 38. DCS results for measuring Tg in top and bottom sections in

PEG400SH1 sample.

The other experiment which has been done to study phase separation effect on

PEG400SH1 sample network is DSC for Tg measurement in two layers (top and bottom

sections) of the same network. The results are presented in Figure 3. 38 and it may be

seen that DSC curves are slightly different in these two sections. (Tg is considered as

middle point of the curve in top layer and is -10.22 °C and in bottom layer is -8.06 °C).

The results reflect the structure differences between two sections of the same network.

This is because when phase separation occurs, the precursor precipitates and is

accumulated in bottom layer of solution which is very concentrated, while the top part is

a more dilute precursor solution. Owing to these concentration differences, the

structures and therefore Tg are different in these two layers.

129

3.2.3.1.5 Effects of Amount of Acidic Water on the Sol-gel Reaction for PEG 400

Network Structures

As mentioned before, hydrolysis and condensation reactions are related to the

amount of water and pH of solution (section 1.5.2). In section 3.2.3.1.2 networks of

PEG 2000 which were synthesized with different amount of 0.1M HCl had different

crosslink structures when the amount of acidic water was changed. In this study the PEG

molecular weight was decreased to 400 Da and the ratio of 0.1 M HCl solution and

silane was kept constant compared to PEG 2000 networks. In this way both types of

reactions could take place in similar conditions and only polymer chains length were

changed.

Figure 3. 39. DSC results (Tg) for PEG 400 networks synthesized with different

amount of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and PEG400SW4)

(The heating rate was 10 °C per min.).


samples were the same, only different amount of acidic water (0.1M HCl) were added to

130

each sample (250 μl: PEG400SW1 , 500 μl: PEG400SW2, 750 μl: PEG400SW3 and

1000 μl: PEG400SW4).

The DSC results in Figure 3. 39 show the glass transition temperature in PEG

400 networks with different amount of 0.1M HCl. The values of Tg are: PEG400SW1: -

8.21 °C, PEG400SW2: -8.74 °C, PEG400SW3: -8.19 °C and PEG400SW4: -9.76 °C

(Figure 3. 39). The glass transition temperatures do not show any trend with increasing

amount of 0.1M HCl solution.

In Figure 3. 40 29Si solid state NMR results show the networks PEG400SW1,

PEG400SW2, PEG400SW3 and PEG400SW4 have similar T2 and T3 structures, and the

intensity of T2 bands are lower than T3. These results differ from the networks

PEG2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4 (Figure 3. 22). In

those networks, the intensity of T2 structures are higher than the intensity of T3

structures. This probably arises because the bis(triethoxy silyl propyl urethane)-PEG

400 has very low water solubility compared to bis(triethoxy silyl propyl urethane) PEG

2000. However, sample PEG400SW1 has higher intensity in T2 structures compared to

T3 structures. This is quite similar to the result of sample PEG2000SW1 (for the

equivalent water and silane ratio).

The shoulders to the left sides of (T2) peaks from -56 to -54 in PEG400 networks

in all four samples are different. This difference between sample PEG400SW1 and the

other three network samples is obvious, because of shape of T2 peak which is sharper

than the other three peaks. Based on the previous results in all PEG 2000 networks,

when shoulder of the left side is smaller, the crosslink density is higher. However in

PEG 400 networks, DSC experiments are not very sensitive compared to PEG 2000

networks due to the absence of crystalline structures in PEG 400 networks. This is

because crystalline structures can change with neighboring chain structures, but Tg is

related to polymer backbone movement at each temperature. This backbone movement

can be hindered or plasticized with chains, crystalline regions or plasticizers, but the

influences of neighboring chains and groups on Tg is lower than the effects on the

crystalline structures (chapter one, section 1.7.1).

131

Figure 3. 40. 29Si Solid State NMR results for PEG 400 networks synthesized with

different amount of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and

PEG400SW4).

To overcome the lower sensitivity of glass transition temperature to the network

structure, the swelling measurement at equilibrium of the network samples in water can

be used. As is shown in Figure 3. 41, the percentage of swelling of networks

PEG400SW1, PEG400SW2, PEG400SW3 and PEG400SW4 in water at equilibrium are

almost equal.

In Figure 3. 42 are shown the sol fraction results in networks PEG400SW1,

PEG400SW2, PEG400SW3 and PEG400SW4. The results show the networks structures

were stable in water up to 45 °C.

132

0

10

20

30

40

50

60


% o

f Sw

ellin

g

Figure 3. 41. Percentage of swelling of PEG 400 networks synthesized with

different amount of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and

PEG400SW4).

0

0.5

1

1.5

2

2.5


% o

f Sol

Fra

ctio

n

Figure 3. 42. Sol fraction in PEG 400 networks synthesized with different amount

of 0.1M HCl (PEG400SW1, PEG400SW2, PEG400SW3 and PEG400SW4).

133


gel Reaction in PEG 4600 Networks

For further consideration of the effects of chain length, PEG 4600 networks were

synthesized with different concentrations of hydrochloric acid. This can illustrate the

effects of a large increase in precursor chain length on network properties.

The reaction conditions in crosslinked PEG 4600 synthesis, as mentioned in

chapter two section 2.4.2.1, for all samples were the same, only different concentration

of HCl were added to each sample (0.001M HCl: PEG4600SH1, 0.01M HCl:

PEG4600SH2, 0.05M HCl: PEG4600SH3 and 0.2M HCl: PEG4600SH4).

In Figure 3. 43 the results of step crystallization method in networks from PEG

4600 synthesized with different concentrations of hydrochloric acid show that even with

long chains, crosslink structures can change the crystalline structure of PEG 4600

networks. When chain length between two junctions increases, the effects of crosslink

structures on overall network properties diminish. As a result, polymer crystalline

structures which are include the central part of chains are closer to crystalline structures

characteristic of the same polymer when it is not crosslinked. The part of chains in

networks which adjacent or close to crosslink junctions have different crystalline

structures compared to the middle part of chains which are located distant from

crosslink junctions. The effect of the crosslink is to cause a small, defective crystalline

region in which the transition temperature is shifted or the endothermic peak is

broadened (Figure 3. 32).

DSC results in Figure 3. 43 for PEG 4600 networks show the crystal transition

temperatures are shifted to higher temperature in samples PEG4600SH1, PEG4600SH2

and PEG4600SH3 (concentration of hydrochloric acid from 0.001 to 0.05 M). These

results suggest that there are effective differences between crosslink structures in

different samples, this effect would be obvious when these temperatures are compared

to the melting point of PEG 4000 which is around 58 °C. The DSC result in

PEG4600SH4 shows two overlapping endothermic peaks, but both are lower than the

temperatures which are expected. This result in PEG 4600 network does not follow the

same trend of result in PEG2000SH4 (PEG 2000 network with 0.2 M acid).

134

Figure 3. 43. DSC results in networks with PEG4600 synthesized with HCl

concentrations from 0.001 to 0.2 M.

The DSC results are compared with results of swelling percentage in water. In

Figure 3. 44 the percentage of swelling of PEG 4600 hydrogels are shown against

concentration of acid used in synthesis.

The percentage of swelling in water at equilibrium increases with increase in

acid concentrations in PEG4600SH1, PEG4600SH2 and PEG4600SH3, but in

PEG4600SH4 the percentage swelling decreases to the lowest value of all four

hydrogels. These results are completely matched with the step crystallization DSC

results and help understand the effects of acid concentrations on network structures. As

mentioned before, the percentage swelling at equilibrium shows whether the networks

structures are loose or tight at the crosslink node as well as the crosslink density.

135

0

50

100

150

200

250

300

350

400


% o

f Sw

ellin

g

Figure 3. 44. Percentage swelling in water of hydrogels which were synthesized with


Figure 3. 45 shows 29Si solid state NMR results for these networks. The results

are not very promising and T2 structures did not show any consistent change with acid

concentration. This may be a limitation of the method due to the lower concentration of

silicon atoms and thus NMR sensitivity. One of the options is synthesis of bis(triethoxy

silyl propyl urethane)-PEG 4600 with 29Si enriched silane to increase concentration of 29Si in crosslink area. The optimum ratio of water to the amount of acid may not be the

linear ratio that was chosen when moving to higher PEG chain length.

The results in Figure 3. 45 show the acid concentrations that were employed

were probably lower than the optimum concentrations. The consequence of a lower

concentration of acid was to produce more T3 structures instead of T2 or in some

conditions T1. When acid concentration increased to 0.05 M a hump at -59 ppm, the T2

structures region, appeared. Although, DSC and swelling results exhibited consistency,

NMR results in 0.001 and 0.01 M networks were not reasonably different compared to

136

swelling results. All the results in network PEG4600SH4 was not very consistent with

other networks and requires further study to understand the reasons for the anomalous

structure.



3.2.3.1.7 Synthesis of Networks Reinforced by Nano-Silica Using Sol-gel

Reactions

All the networks that were synthesized in previous sol-gel reactions were in the

absence of deliberately added, pre-formed nano-silica. Nano-silica is routinely used as a

reinforcing agent in silicone elastomers and in this section the effects of addition of

nano-silica on the network structure and properties will be discussed. For sol-gel

reactions, the existence or formation of silanol groups (Si-OH) during hydrolysis

reactions are essential for condensation reactions. These silanol groups are available on

the surface of hydrophilic silica. As discussed earlier in chapter one, section 1.6.2,

hydrophilic silica and bis(triethoxy silyl propyl urethane)-PEG precursor can undergo

alcohol-producing condensation in the absence of water under absolute dry conditions as

well as both alcohol- and water-producing condensation reactions in the presence of

water. However, network formation in the absence of water cannot be achieved due to a

diffusion-controlled reaction mechanism. For the synthesis of networks reinforced with

137

silica, some PEG polymer chains chemically bind to the surface of silica and the rest can

make crosslink structures with sol-gel reaction. To achieve dispersion, as mentioned in

chapter two, section 2.4.2.1, neat silica was suspended in methanol and sonicated for

several minutes to an hour until the suspension became homogenous and a little hazy

(At the beginning, the suspension was completely opaque). Then bis(triethoxy silyl

propyl urethane) PEG precursor was added to suspension and again it was sonicated for

several minutes to get a clear polymer-silica suspension. In this stage silica particles

were stabilized in methanol with silica-PEG interaction due to hydrogen bonding. This

interaction helped to remove methanol from suspension without aggregation occurring.

In the further stage of reaction crosslinked structures were formed with sol-gel reaction

between either silica and precursor or precursor end groups. (The reaction was explained

in chapter two, section 2.4.2.1, in detail).

3.2.3.1.7.1 Synthesis of Reinforced Networks with Hydrophilic Silica Using a Sol-

gel Reaction

The reactions with silica in this section are very similar to reactions without

silica in networks.

The reaction conditions for synthesis of reinforced networks with PEG 2000, as

mentioned in chapter two, section 2.4.2.1, were the same for all samples, only different

percentage of silica were added to each sample (0% silica: PEG2000SWS0, 1% silica:

PEG2000SWS1, 5% silica: PEG2000SWS5, 10% silica: PEG2000SWS10 and 20%

silica: PEG2000SWS20).

The step crystallization DSC experiments in Figure 3. 46 show the crystal

transition temperature in networks for different amount of hydrophilic silica (from 0 to

20%). The maximum transition temperature occurs in the sample PEG2000SWS0 and

the minimum transition temperature appears in PEG2000SWS20. Samples

PEG2000SWS1 and PEG2000SWS5 show very similar transition temperatures.

However, in these two networks two overlapping peaks are observed which indicates

that different crystalline structures were in the samples. In PEG2000SWS10 and

PEG2000SWS20 only one broad peak was observed. All these results show effects of

silica on the crystalline structures which can be a nucleation effect (even though the size

138

of silica particles is very small) in spite of constraining effect of crosslink node (Figure

3. 47). The effects of crosslink nodes were discussed earlier in this chapter, section

3.2.3.1.1.

Figure 3. 46. Step crystallization DSC results of reinforced networks with different

percentage of silica.

In Figure 3. 47 crystalline structures in the presence and absence of crosslinking

and silica are shown. As shown in this figure, crystalline structures in crosslinked

polymer are different compared to crystalline structures in linear polymer. As shown in

Figure 3. 47 b, there is a restricted crystalline region between two crosslinking junctions

due to lower degree of freedom at chain ends where these are not able to pack into

crystalline regions. As shown in Figure 3. 47 c, polymer chains may pack in a crystalline

region with a nucleation mechanism in which silica particles act as the nucleation agent.

This alteration in crosslink structure can be examined with 29Si NMR, DSC results and

swelling measurements at equilibrium. During nucleation and crystal growth, when the

number of nucleation events increases, the size of crystalline domains decreases [26].

139

This effect can be observed in Figure 3. 46. As seen in this figure, in PEG2000SWS0

the crystal transition temperature appears at highest temperature among all reinforced

networks, and it shows the sharpest endotherm. When the fraction of silica increases

from 1% to 20% (PEG2000SWS1, PEG2000SWS5, PEG2000SWS10 and

PEG2000SWS20), the crystal transition temperatures shift to lower temperature.

Figure 3. 47. (a) ‘Ideal’ crystalline structure in linear polymer from polymer

solution. (b) Crystalline structure in crosslinked polymer. (c) Crystalline structure

in crosslinked polymer with silica.

140


different percentage of added silica

The results of 29Si solid state NMR of all PEG 2000 networks with different

percentage silica and neat silica A300 are shown in figure 3.63. As mentioned earlier in

section 3.2.2.2.1, silica has Q structures (Q1, Q2, Q3 and Q4) while in situ silsesquioxane

which is made from bis(triethoxy silyl propyl urethane)-PEG has only T structures due

to one carbon atom being adjacent to the silicon atom.

In networks without silica, T3 structures and T1 structures peaks are smaller

compared to other networks with silica. In all the networks with added silica the peaks

attributed to T3 structures and T1 structures increase. The peak in T2 structures gets

broader from PEG2000SWS0 to PEG2000SWS20. This change occurs from -57 to -54

ppm (left side shoulder in T2 structures peak). These changes in all T structures may be

attributed to the addition of hydrophilic silica which has silanol on the surface. To show

the effects of silica particles on the T structures, the reaction between the silica surface

and the precursor needs to be confirmed. In Figure 3. 48 Q structures are shown from

around -115 to -90 ppm [7-9]. If Q structures (Q2, Q3 and Q4) in silica A300 as received

are compared with Q structures in silica inside the networks, the NMR spectra show Q2

and Q3 changed to Q3 and Q4. In other words, during reaction Q2 species on the surface

changed to Q3 due to reaction between silica and bis(triethoxy silyl propyl urethane)-

141

PEG and Q3 reacted with another precursor to form a Q4 structure. This supports the

reaction between the added silica and the network so this silica can act as an active

reinforcement in the synthesis of reinforced networks.

In Figure 3. 49 the percentage swelling of reinforced hydrogels in water for

different percentage of silica is shown. A correction needs to be applied since the

hydrogels contain different amount silica and during the swelling process PEG part of

hydrogels can be swollen, but silica particles are solid and cannot absorb water. To

correct for this, the swelling results based on net PEG in hydrogels without the weight of

silica are calculated. The percentages of swelling in reinforced hydrogels are then seen

to decrease with increase in the percentage of silica. The same trend was observed in

DSC experiments in Figure 3. 46. This shows that by increasing the silica content, the

crystal transition temperature shifts to lower temperature. The reason that swelling

percentages decrease even after correction for the mass of added silica is because silica

0

50

100

150

200

250

300

PEG2000SWS0 PEG2000SWS1 PEG2000SWS5 PEG2000SWS10 PEG2000SWS20

% o

f Sw

ellin

g

With silica Without Silica

Figure 3. 49. Percentage swelling of reinforced hydrogels in water (calculation with

and without silica and average error bars from section 3.2.3.1.2, Figure 3. 25) for

different percentage of silica (from 0 to 20%).

142

increases modulus of polymer and as a result, the swelling deformation of polymer

chains needs a higher force. This force develops higher osmotic pressure (elastic force)

inside reinforced compared to non-reinforced hydrogels. This higher osmotic pressure

drops the swelling percentage at equilibrium. At equilibrium, the osmotic pressure of

water inside and outside of hydrogels become equal and at this point the rate of water

absorption and release become equal [27]. The other reason for decreasing swelling

percentage can be hydrogen bonding between A300 silica and PEG backbone in

hydrogels. The interaction between A300 silica and PEG can act as a physical

crosslinker to limit the percentage of swelling.

Results for the percentage of sol fraction show PEG 2000 hydrogels with silica are very

stable in water at 45 °C (Figure 3. 50).

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1


% o

f Sol

Fra

ctio

n

Figure 3. 50. Sol fraction in reinforced PEG2000 hydrogels that were synthesized

with different amounts of silica (from 0 to 20%).

143

3.2.3.1.7.2 Synthesis of Crosslinked PEG 400 Reinforced with Hydrophilic Silica

Using a Sol-gel Reaction

Low molecular weight PEG such as PEG 400 potentially cannot be a network

with a high swelling ability because of its high crosslink density (as mentioned in

section 3.2.3.1.5). In this section the effect of silica on the structure and swelling

properties of reinforced PEG 400 networks will be discussed.

The reaction conditions in reinforced networks PEG 400 synthesis, as mentioned

in chapter two, section 2.4.2.1, were the same for all samples, only different percentage

of silica were added to each sample (0% silica: PEG400SWS0, 1% silica:

PEG400SWS1, 5% silica: PEG400SWS5, 10% silica: PEG400SWS10 and 20% silica:

PEG400SWS20).

Figure 3. 51. DSC results (Tg) for networks from PEG 400 that were synthesized

with different amount of silica (the heating rate was 10 °C per min.).

144

In Figure 3. 51 the DSC traces and glass transition temperatures of these

networks are shown. The results do not have any clear relationship against the

percentage of silica.

The results of a 29Si NMR study of PEG 400 networks with different amount of

silica are shown in Figure 3. 52. By adding silica to PEG 400 networks during synthesis

the peak attributed to the T3 structure is smaller compared to that in PEG 400 network

without silica. The intensity of T2 becomes higher by adding silica into crosslinked

PEG400. This suggests that the added silica changed the silane-produced silica

structures (in situ silsesquioxane) from T3 to T2 and T1. This change appears in network

PEG400SWS1 which shows crosslink structures in sol-gel reaction can dramatically

change in the presence of silica.

Figure 3. 52. 29Si Solid State NMR spectra from PEG 400 networks that were

synthesized with different percentage of silica.

Swelling percentages in PEG 400 networks after adding silica dropped and

changed only slightly with silica content (Figure 3. 53) compared to PEG 2000

networks. This is because the chain lengths are too short for the swelling percentage to

145

be altered with the amount of silica added. However, silica in PEG400 networks can

decrease the percentage of swelling.

These structural changes were observed in 29Si NMR spectra in both PEG 400

and PEG 2000 networks (Figure 3. 48 and Figure 3. 52). These changes are not

completely similar in both groups of PEG 400 and 2000 networks due to lower

solubility of bis(triethoxy silyl propyl urethane)-PEG 400 and viscosity effects during

PEG 400 network synthesis.

The sol fraction results show PEG 400 networks with silica are stable in water at

45 °C and condensation reaction had taken place with reasonable yield (Figure 3. 54).

0

5

10

15

20

25

30

35

40

45

50


% o

f Sw

ellin

g

With silica Without silica

Figure 3. 53. Percentage of swelling in reinforced networks (calculation with and

without silica) versus percentage of silica.

146

0

0.5

1

1.5

2

2.5

3

3.5


% o

f Sol

Fra

ctio

n

Figure 3. 54. . Sol fraction in PEG 400 networks which were synthesized with

different amount of silica.

3.2.3.1.7.3 Synthesis of Crosslinked PEG 400 Reinforced with Hydrophilic Silica

in Sol-gel Reaction with Different Acid Concentration

The results for PEG 400 networks with different percentage of silica show the

effect of silica on the crosslink structures. To examine these effects, a fixed amount of

silica was used with different concentration of acid.

The reaction conditions in reinforced networks PEG 400 synthesis, as mentioned

in chapter two, section 2.4.2.1, for all samples were the same and fixed amount of silica

at 5%, only different concentration of HCl solution were added to each sample (0.001M

HCl: PEG400SH1S5, 0.01M HCl: PEG400SH2S5, 0.05M HCl: PEG400SH3S5 and

0.2M HCl: PEG400SH4S5).

147

Figure 3. 55. DSC results (Tg) for networks from PEG 400 with 5% silica which

were synthesized with different concentration of HCl (from 0.001M to 0.2M HCl).

The Tg results (the heating rate was 10 °C per min.) illustrate shifts with increase

of acid concentration from 0.001 to 0.2 M (from PEG400SH1S5 to PEG400SH4S5)

(Figure 3. 55).

The glass transition temperatures (middle point of DSC curve) increase with

increase in the concentration of acid (Figure 3. 55) whereas they were expected to

decrease with increase acid concentration. It is expected that when acid concentration

increases, crosslinked structures become less tight and Tg would therefore shift to lower

values. The reason for the opposite effect is unknown and it needs more investigation

with both DSC and DMTA techniques to measure the glass transition temperature

precisely.

29Si NMR results can show crosslink structure changes when concentrations of

acid increase in the presence of fixed amount of silica. In Figure 3. 56 the peak

attributed to T3 structures slightly changes and becomes two overlapping peaks with

148

decrease in the amount of acid and is particularly apparent in the samples

PEG400SH1S5 and PEG400SH2S5. T2 structures also increase with dropping acid

concentration. These changes in NMR peaks do not match the results in normal PEG

400 network which were synthesized with different concentration of acid (Figure 3. 35).

However, T1 structures appear at low acid concentration which is matched by the

mechanism and rate of hydrolysis at pH around 7. This is because the hydrolysis

reaction rate is very slow around pH 7and T1 structures can be formed at end groups of

T2 and T3 structures [8].

The 29Si NMR results confirm crosslink structures in the presence of silica are

more stable in acidic condition compared to crosslink structures in non-reinforced

networks (Figure 3. 56). In other words, during pH changes the crosslink structures

without silica change more than structures when precursor reacts with silica. According

to Brook, in acidic conditions first a chain extension reaction takes place, then grafting

to the surface of hydrophilic silica occurs [23]. Silica can stop further development of

chain extension and crosslinking processes and grafting reactions take preference as

network formation takes place. As mentioned in chapter one, section 1.5.2, condensation

reaction may take place preferentially between protonated silanols on monomers

(precursor) and end groups which cause chain extension. Replacement of electron-

providing alkoxide group with more electron-withdrawing OH and O-Si groups can

destabilize the positive charged intermediate and retard the condensation reaction in

acid-catalyzed condensation.

In other words, in low pH (acidic conditions) chain extension reactions between

precursors are the preferential reaction compared to reaction between silanol on the

surface of silica. This mechanism may become reversed in base-catalyzed condensation

reaction due to more O-Si groups stabilizing the negative charge on core silicon atom

and so enhance the reaction between precursors and silanol on the surface of silica

which is mostly Q3 (based on NMR results and nano-silica). This is because Q4 is very

unstable on the surface of silica and it has to be situated in the bulk, however, in nano-

silica Q2 and Q3 structures have higher fraction compared to Q4 due to low size and high

surface area.

149

Figure 3. 56. 29Si Solid State NMR spectra in reinforced PEG 400 networks (5%

silica) were synthesized with different concentrations of acid (HCl).

3.2.3.1.7.4 Network Formation with Base-catalyzed Hydrolysis and Condensation

Reactions

Base-catalyzed network formation was examined only for comparison with the

acid-catalyzed networks. This is because bis(triethoxy silyl propyl urethane)-PEG

precursor which reacts in acidic conditions has, in terms of color change, less

degradation compared to reaction under highly basic conditions.

As shown in Figure 3. 57, the crystal transition temperature in network that was

synthesized with NH4OH (PEG2000SW5) is the highest among all networks, sample

PEG2000SW3 is the second highest and the lowest is sample PEG2000SW1.

150

Figure 3. 57. DSC results of networks in samples PEG2000SW1, PEG2000SW3 and

PEG2000SW5 (base and acidic catalysts).

The results in 29Si Solid State NMR in Figure 3. 58 show when pH of solutions

change from strong acidic condition to mild (PEG2000SW1 and PEG2000SW3), T3

structures increase compared to T2 and T3 peak shifts toward -68 ppm. This increase in

T3 compared to T2 continues with changing acidic catalyst to base catalyst

(PEG2000SW1 and PEG2000SW5). These changes match the theory (as described at

chapter one, section 1.5.2) which explains effects of pH on in situ silsesquioxane

structures. The peak around -49 ppm is for T1 structures which can occur through chain

extension or as end groups of T2 and T3 structures. The other factor which needs to be

considered is the amount of water. The networks PEG2000SW3 and PEG2000SW5

were synthesized with the same amount of water. However in PEG2000SW1 three times

less water was added in to the precursor solution during synthesis. This lower amount of

water added can change the structures.

151

Figure 3. 58. 29Si Solid State NMR spectra in PEG 2000 networks were synthesized

with different acidic and base catalysts (PEG2000SW1, PEG2000SW3 and

PEG2000SW5).

Percentages of swelling in water at equilibrium are shown in Figure 3. 59. If

synthesis with base-catalyst has the same mechanism of crosslink formation, the

percentage of swelling in hydrogel PEG2000SW5 must have the lowest percentage of

water absorption in all these hydrogels. However, the lowest water absorption was

observed in hydrogel PEG2000SW1. Based on step crystallization results the highest

amount of water absorption must occur in PEG2000SW5 sample, because it shows the

highest crystal transition temperature. The highest percentage of swelling is in this

hydrogel, but difference between hydrogels PEG2000SW5 and PEG2000SW3 is only

small. The swelling result and the crystal transition temperature result in PEG2000SW1

are in agreement and both of the results are the lowest in values between all three

hydrogels. Based on these results from DSC, swelling measurement and 29Si NMR, it

may be that small T3 structures species were formed. This is because these T3 structures

can be smaller than T2 which make clusters of a combination of T2 and T1. As a result,

in situ silsesquioxane structures (T3) are formed by sol-gel reaction between a small

152

number of bis(triethoxy silyl propyl urethane)-PEG2000 precursors, and network

(PEG2000SW5) shows a higher crystal transition temperature and swelling percentage

in water at equilibrium [28].

0

50

100

150

200

250

300

PEG2000SW5 PEG2000SW1 PEG2000SW3

% o

f Sw

ellin

g

Figure 3. 59. Percentage of swelling in hydrogels PEG2000SW1, PEG2000SW3 and

PEG2000SW5.

Sol fraction result (Figure 3. 60) shows all three hydrogels are fairly stable in

water at 45 °C for more than two days, however, these results show the hydrogels which

were synthesized by acidic catalyst (PEG2000SW1 and PEG2000SW3) are more stable

compared to PEG2000SW5. This can possibly be caused by formation of cyclic trimers

(Si-O-Si) at relatively high pH (around pH 12), which are less stable at lower pH due to

reduced Si-O-Si bond angles and build-up of strain on the bond [8, 29]. Sol fractions

and swelling measurement have been performed at pure water with pH lower than

synthesis condition in sample PEG2000SW5.

153

0

0.5

1

1.5

2

2.5

3

PEG2000SW5 PEG2000SW1 PEG2000SW3

% o

f Sol

Fra

ctio

n

Figure 3. 60. Sol fraction in PEG 2000 hydrogels PEG2000SW1, PEG2000SW3 and

PEG2000SW5.

3.2.3.1.7.5 Network Formation with TEOS as Crosslinker

In sections 3.2.3.1, 3.2.3.1.1 and 3.2.3.1.2, crosslinking takes place through the

end groups of bis(triethoxy silyl propyl urethane)-PEG (precursor). In the presence of

hydrophilic silica, silanol on the surface of silica acts as a weak crosslinking agent to

form three-dimensional networks. There is another possibility to form in situ

silsesquioxane particles inside a PEG network (in situ silsesquioxane formation) by the

introduction of a tetrafunctional monomer such as tetraethyl orthosilicate (TEOS) to co-

react with bis(triethoxy silyl propyl urethane)-PEG precursor. Both types of silane

(TEOS and precursor) undergo sol-gel reaction and form three-dimensional networks as

well as in situ silsesquioxane particle in which the size and structure of silica particle are

related to reaction conditions (pH, water and temperature) and TEOS concentration. The

method that has been used to make PEG-silica networks by other researchers [30] is to

employ tetraethyl orthosilicate (TEOS) as a co-crosslinker which can undergo

hydrolysis and condensation reactions with silane at the end of precursor chains. (This

154

feature is the main difference between the novel method that has been developed in this

project and the previous research using bis(triethoxy silyl propyl urethane)-PEG and

TEOS sol-gel reaction). Synthesis method in samples PEG2000SH2TS,

PEG2000SH3TS, PEG4600SH2TS and PEG4600SH3TS were described in chapter two,

section 2.4.2.1.

Figure 3. 61. Step crystallization (DSC) in networks PEG2000SH2,

PEG2000SH2TS, PEG2000SH3 and PEG2000SH3TS.

155

Figure 3. 62. Step crystallization (DSC) in networks PEG4600SH2,

PEG4600SH2TS, PEG4600SH3 and PEG4600SH3TS.

As mentioned in section 2.4.2.1, around 6.5 mg TEOS was added to each

sample. The reason a very small amount of TEOS was introduced to the solutions was to

make minimal change to r (molar ratio of water to silane).

DSC step crystallization results are shown in Figure 3. 61 and Figure 3. 62 for

samples (with and without TEOS): PEG2000SH2TS, PEG2000SH3TS,

PEG4600SH2TS, PEG4600SH3TS, PEG2000SH2, PEG2000SH3, PEG4600SH2 and

PEG4600SH3. In all networks with TEOS the crystal transition temperatures slightly

156

shifted to higher temperature compared to networks without TEOS. Changes in

crosslink structures can be observed in 29Si NMR results on PEG 2000 networks (Figure

3. 63).

Figure 3. 63. 29Si Solid State NMR spectra in PEG 2000 networks that were

synthesized with 0.01M HCl (a) (PEG2000SH2 and PEG2000SH2TS) and 0.05 M

HCl (b) (PEG2000SH3 and PEG2000SH3TS) (with and without TEOS).

29Si NMR results on networks PEG2000SH2 and PEG2000SH3 exhibit left

shoulders in T2 structures (from -57 to -54 ppm), but when a very small amount of

TEOS (samples PEG2000SH2TS and PEG2000SH3TS) was added this shoulder in both

groups of networks disappeared.

The results of percentage of swelling in water at equilibrium (Figure 3. 64 and

Figure 3. 65) showed only minor changes occurred when TEOS was added to precursor

solutions. Addition of TEOS causes decrease in swelling percentages which may affect

the trend between swelling percentage and concentration of acidic catalyst ([HCl]) in

synthesis solutions. The effects [HCl] and [H2O] added need more investigation,

because addition of TEOS can change all ratios between Si and water and acid

concentrations. However, results in NMR and DSC and clearly suggest that crosslink

157

structures can change in the presence of TEOS. The results in DSC and NMR show

significant differences between with and without TEOS compared to the results in

swelling experiments. This is due to the small amount of TEOS addition (6-7 mg).

0

50

100

150

200

250

PEG2000SH2 PEG2000SH2TS PEG2000SH3 PEG2000SH3TS

% o

f Sw

ellin

g

Figure 3. 64. Percentage of swelling in hydrogels PEG2000SH2, PEG2000SH2TS,

PEG2000SH3 and PEG2000SH3TS.

0

50

100

150

200

250

300

350

400

PEG4600SH2 PEG4600SH2TS PEG4600SH3 PEG4600SH3TS

% o

f Sw

ellin

g

Figure 3. 65. Percentage of swelling in hydrogels PEG4600SH2, PEG4600SH2TS,

PEG4600SH3 and PEG4600SH3TS.

158

3.3 Summary and Final Discussion

The research that has been performed in this section mainly focused on the

formation of novel silsesquioxane structures as a type of crosslinker through a sol-gel

reaction in acidic conditions. The advantage of the silsesquioxane crosslinker is the

ability to alter and control the network structure and swelling properties with simple

changes in sol-gel reaction conditions, in spite of a constant polymer chain length (ie.

PEG of molecular weight 2000Da).

Formation of the silsesquioxane crosslinker can take place with change in the

amount of certain HCl solution or simply with change in HCl concentration. All of these

possibilities were described early in this Chapter and came from different methods of

synthesis of in situ silsesquioxane structure and alteration to the size and structure

through sol-gel reactions which led to polymer network connectivity changes (mesh

size) [1, 6-10, 23, 28-37]. As the results showed, swelling percentage as well as network

properties underwent systematic changes with the amount or concentration of HCl. This

is due to differences in the rate of reaction between hydrolysis and condensation

reactions (as discussed earlier).

The structural changes and effects have been examined through the step-

crystallization DSC (crystal transition temperatures), DMTA (α- and α’-transition

temperatures), 29Si solid state NMR (T and Q structures) and swelling measurement

(mesh size) techniques. The other advantage in this method of synthesis is the reaction

between silanol groups on the surface of a hydrophilic silica and precursors

(bis(triethoxy silyl propyl urethane)-PEG) to form a silsesquioxane crosslinker during

sol-gel reaction [23]. In this process silica acts as an active filler due to chemically

bonding to the polymer network. This surface reaction can clearly be proven by

employing 29Si solid state NMR [6, 38]. The step crystallization DSC and swelling

measurement technique have been employed to characterize the networks structures (as

the results and discussions were given earlier) [26].

Dangling chains and loose (slack) chains effects on network properties was

another aspect of this research in this chapter. Dangling chains and loose chains have

two absolutely different effects on crystalline and amorphous polymers. PEG networks

159

in both dry and swollen conditions were examined. The dry networks were analyzed

with DSC and the swollen hydrogels were studied by the percentage of swelling at

equilibrium in water. Based on 29Si solid state NMR all samples showed very close

silsesquioxane crosslinker structures and no evidence about loose chains (chain

extension reaction) were seen (to the limit of 29Si solid state NMR sensitivity). This is

one of the advantages in silsesquioxane network formation through the sol-gel reaction.

Networks with known percentage of dangling chain were synthesized by introduction of

different percentage of triethoxy silyl propyl urethane-PEG. Dry networks crosslink

structures (29Si NMR), crystalline region structures (SC-DSC) and percentage of

swelling in water in these networks were analyzed. (The results and discussion have

been given in section 3.2.3.1.2).

Water solubility of precursor is important in sol-gel method of synthesis. As

mentioned earlier (section 1.5.2 [8, 10]) both hydrolysis and condensation reactions are

first-order in [H2O] in acid-catalyzed reactions. When the precursor chain length gets

shorter, end groups, which are less water soluble compared to PEG chain, can dominate

the reaction outcome. When water solubility of the precursor decreases, the swelling

percentage of hydrogels at equilibrium becomes independent of the addition of the water

added during synthesis. This independency is because of phase separation in the water-

precursor solution. These results were examined by employing bis(triethoxy silyl propyl

urethane)-PEG 400 precursor.

Another advantage of network synthesis by the sol-gel method is the reaction may occur

over a large range of pH in aqueous solution. It is therefore possible to use this method

of synthesis for drug encapsulation in networks during crosslinking process, when the

drug is only stable in certain range of pH. The main disadvantage of sol-gel reactions is

the long time taken for complete reaction (as mentioned in chapter two, section 2.4.2.1)

compared to bis acrylate PEG network synthesis (as mentioned in chapter two, section

2.4.3).

160

References 1. Torry, S.A., Campbell, A., Cunliffe, A.V. and Tod, D.A., Kinetic Analysis of

Organosilane Hydrolysis and Condensation. Int. J. Adhes. Adhes., 2006. 26(1-2): p. 40-49.

2. Saint-Loup, R., J.-J. Robin, and B. Boutevin, Synthesis of Poly(ethylene terephthalate)-block-Poly(tetramethylene oxide) Copolymer by Direct Polyesterification of Reactive Oligomers. Macromolecular Chemistry and Physics, 2003. 204(7): p. 970-982.

3. Rutnakornpituk, M., Ngamdee, P. and Phinyocheep, P., Synthesis, characterization and properties of chitosan modified with poly(ethylene glycol)-polydimethylsiloxane amphiphilic block copolymers. Polymer, 2005. 46(23): p. 9742-9752.

4. Daniel-da-Silva, A.L., Bordado, J. C. M. and Martýń-Martýńez, J. M., Moisture Curing Kinetics of Isocyanate Ended Urethane Quasi-Prepolymers Monitored by IR Spectroscopy and DSC. J. Appl. Polym. Sci., 2008. 107: p. 700-709.

5. Derosa, R.L., Trapasso, J. A., Poly(ethylene glycol) interactions with alumina and silica powders determined via DRIFT. J. Mater. Sci., 2002. 37: p. 1079-1082.

6. Maher, J.M., Cooper, N. J., Silicon-29 NMR study of the surface of silica gel by cross polarization and magic-angle spinning. J. Am. Chem. Soc., 1980. 102: p. 7606-7607.

7. Jal, P.K., Patel, S. and Mishra, B.K., Chemical modification of silica surface by immobilization of functional groups for extractive concentration of metal ions. Talanta, 2004. 62: p. 1005–1028.

8. Brinker, C.J., Scherer, G. W., Sol-gel science, the physics and chemistry of sol-gel processing. 1989, San Diego: Academic Press.

9. Singh, R.P., Way, J. D. and Dec, S. F., Silane modified inorganic membranes: Effects of silane surface structure. Journal of Membrane Science, 2005. 259: p. 34–46.

10. Iler, R.K., The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties,and Biochemistry. 1979, New York: John Wiley and Sons.

11. Odian, G., Principles of Polymerization, ed. Fourth. 2004, Hoboken: John Wiley & Sons, Inc., Publication.

12. Sperling, L.H., Introduction to Phsycal Polymer Science. 4th ed. 2006, New Jersey: John Wiley & Sons, Inc.

13. Iza, M., et al., Hydrogels of poly(ethylene glycol): mechanical characterization and release of a model drug. Journal of Controlled Release, 1998. 52(1-2): p. 41-51.


15. Nielsen, L.E., Landel, R. F., Mechanical Properties of Polymers and Compsites. 2nd ed. 1994, New York: Marcel dekker, Inc.

16. Bicerano, J., Prediction of Polymer Properties. Second ed. 1996, New York: Marcel Dekker, Inc.

161

17. Sugahara, Y., Inoue, T. and Kuroda, K, 29Si NMR Study on Co-hydrolysis Processes in Si(OEt)4–RSi(OEt)3–EtOH–Water–HCl Systems (R=Me, Ph): Effect of R Groups. J. Mater. Chem., 1997. 7(1): p. 53-59.

18. Elbert, D., Pratt, A., Lutolf, M., Halstenberg, S. and Hubbell, J., Protein Delivery from Materials Formed by Self-Selective Conjugate Addition Reactions. J. Controlled Release, 2001. 76: p. 11-25.

19. Flory, P., Rehner, J., Statistical Mechanics of Cross-Linked Polymer Networks II. Swelling. J. Chem. Phys., 1943. 11(11): p. 521-526.

20. Patel, S., Malone, S., Cohen, C., Gillmor, J. and Colby, R., Elastic Modulus and Equilibrium Swelling of Poly(dimethylsiloxane) Networks. Macromolecules, 1992. 25(20): p. 5241-5251.

21. Hennink, W., Talsma, H., Borchert, J. De Smedt, S. and Demeester, J., Controlled Release of Proteins from Dextran Hydrogels. J. Controlled Release, 1996. 39: p. 47-55.

22. De Smedt, S., Lauwers, A., Demeester, J., Van Steenbergen, M., Hennink, W. and Roefs, S. P. F. M., Characterization of the Network Structure of Dextran Glycidyl Methacrylate Hydrogels by Studying the Rheological and Swelling Behavior. Macromolecules, 1995. 28(14): p. 5082-5088.

23. Brook, M., A., Silicon in Organic, Organometallic, and Polymer Chemistry. 2000, New York: John Wiley & Sons, Inc.

24. Halley, P.J., George, G. A., Chemorheology of Polymers, From fundamental Principles to Reactive Processing. 2009, New York: Cambridge University Press.



27. Padmavathi, N.C., Chatterji, P., Structural Characteristics and Swelling Behavior of Poly(ethylene glycol) Diacrylate Hydrogels. Macromolecules, 1996. 29: p. 1976-1979.

28. Knight, C.T.G., R.J. Balec, and S.D. Kinrade, The Structure of Silicate Anions in Aqueous Alkaline Solutions13. Angewandte Chemie International Edition, 2007. 46(43): p. 8148-8152.

29. Dent-Glasser, L.S., Lachowski, E. E., Silicate Species in Solution. Part 1. Experimental Observations. J. Chem. Soc. Dalton Trans., 1980: p. 393-399.

30. Kweon, J., Noh, S., Thermal and Thermomechanical Properties of Poly(ethylene oxide) Networks Produced with Silica and Organic Crosslinking Agents. J. Appl. Polym. Sci., 2003. 90: p. 270-277.

31. Voronkov, M.G., Mileshkevich, V. P. and Yuzhelevski, Y. A., The Siloxane Bond. 1978, New York: Consultants Bureau.

32. Swain, C.G., Esteve, R. M. and Jones, R. H., Organosilicon Chemistry: The Mechanisms of Hydrolysis of Triphenylsilyl Fluoride and Triphenylmethyl Fluoride in 50% Water-50% Acetone Solution. J. Am. Chem. Soc., 1949. 71: p. 965-971.

162

33. McNeill, K.J., DiCaprio, J. A., Walsh, D. A. and Pratt, R. F., Kinetics and Mechanism of Hydrolysis of a Silicate Triester, Tris( 2-methoxyethoxy )phen ylsilane. J. Am. Chem. Soc., 1980. 102(6): p. 1859-1865.

34. Grubb, W.T., A Rate Study of the Silanol Condensation Reaction at 25° in Alcoholic Solvents. J. Am. Chem. Soc., 1954. 76: p. 3408-3414.

35. Barbe´, C., Bartlett, J., Kong, L., Finnie, K., Lin, H. Q., Larkin, M., Calleja, S., Bush, A. and Calleja, G., Silica Particles: A Novel Drug-Delivery System. Adv. Mater., 2004. 16: p. 1959-1966.

36. Aelion, R., Loebel, A. and Eirich, F., Hydrolysis of Ethyl Silicate. J. Am. Chem. Soc., 1950. 72: p. 5705-5712.

37. Pohl, E.R., Osterholtz, F. D., Molecular Characterization of Composite Interfaces, ed. H. Ishida, Kumar, G. 1985, New York.

38. Büchele, J., Marzini, M. and Mayer, H. A., Stationary phases composed of sol–gel processed organometallic complexes functionalized with polyethylene glycol. J. Chem. Soc. Dalton Trans., 2003: p. 4107-4114.

163

Chapter 4: Study of the Interface of Silica and

Polymer in Nano-silica Reinforced Networks

4.1 Introduction

As mentioned in chapter one, section 1.6, in advanced polymer technology and

industry, polymer materials without additives and reinforcement have very limited

applications. Most recently, the performance of polymeric materials has been enhanced

by nano-composites technology.

Nano-composite technology is highly related to surface chemistry modification,

state of dispersion of nano-particles and particle loading [1]. In other words, the special

challenges in nano-composites technology are to achieve a certain level of dispersion of

the nano-particles in the polymeric matrix, a sufficient interfacial bond and maximum

nano-structural influences such as surface area [2]. To tackle the undesirable

agglomeration there are several techniques that can be used. The first is high shear force

during mixing to segregate particles and the second method is surface functionalization.

In surface functionalization, as described in chapter one, section 1.6.2 and

chapter three, section 3.2.2, the surfaces of particles are treated with coupling agents

such as organosilanes. One functional group (eg the silyl alkoxy group) of this

compatibilizer reacts with surface of nano-particles, the other organofunctional group

interacts through van der waals forces, hydrogen bonding or covalent bonding with the

polymer. Those coupling agents that can increase particle-polymer adhesion cause an

increase in mechanical properties such as Young’s modulus [3].

In this chapter the effects of silica on reinforced PEG-based networks and

interfacial influences in terms of interaction between coupling agents and the bulk PEG

networks will be discussed.

164

4.2 Reinforced Networks and Interfacial Properties

4.2.1 Requirements for the Study of Interfacial Properties of Reinforced

Networks

There are several methods for studying the effects of reinforcing agents on

polymer composites. Dynamic mechanical thermal analysis (DMTA) is the method that

was applied in this research. As mentioned in chapter one, section 1.8, the advantage of

this technique is the measurement of both modulus and tan δ at the same time. Modulus

changes can show the reinforcement effects of silica on networks over a large range of

temperature in a low deformation. Moreover, tan δ will undergo shifts in the relaxation

temperatures in composites that reflect interactions between either neat nano-silica

surface and PEG or coupling agents on the surface of silica and PEG. Step

crystallization method in DSC was employed to complement the results which were

collected with DMTA.

However the disadvantage of DMTA which makes it a difficult and sophisticated

technique to use is operational issues. The main issue is sample preparation and sample

shape. The samples need to be made in very precise geometrical shapes such as disks or

bars. The test results can be badly affected when the geometry is not precise.

For dealing with sample preparation difficulties, a UV curing method was

applied (free radical polymerization as mentioned in chapter one, section 1.5.1) and the

UV crosslinking reaction took place in a glass slides-silicone rubber mould (chapter

two, section 2.4.3).

4.2.2 Synthesis of Bis acrylate- PEG Precursor

As mentioned in chapter one, section 1.4.2.2, hydroxyl groups at both ends of

PEG need to be replaced with a UV-active functional group to achieve a fast curing

method for network synthesis. In this project bis acrylate PEG was synthesized using

acryloyl chloride and PEG reaction in absolutely dry conditions (chapter two, section

2.3) [4]. The purified bis acrylate PEG, was examined with 1H-NMR in CDCl3 to

determine both yield of esterification reaction and acrylate group existence (Figure 4. 1).

The yield of ester in all the reactions was above 97% based on PEG backbone (in most

165

reactions it was 99 to 100%), however, in some reactions the yield based on acrylate

groups was lower than 90%.

The lower percentage of acrylate functional groups in the precursor can lead to

different crosslink structure in final network products. This is because free radical

polymerizations are sensitive to monomer (bis acrylate PEG precursor) radical

formation. In Figure 4. 1 1H-NMR result for bis acrylate PEG 2000 after purification

shows the yield of acrylation substitution was 98.5% and in acrylate group was 93% [4].

In this project, precursor with yield above 90% based on acrylate group was used.

Figure 4. 1. 1H-NMR of bis acrylate PEG 2000 after purification

4.2.3 Synthesis of Networks from Bis acrylate PEG

As mentioned in chapter one, section 1.5.1, the relative rates of the initiation,

propagation and termination reactions affect network final structure [5, 6]. The other

factor that needs to be considered is viscosity rise during crosslinking reactions. When

the PEG solution changes to a very high viscosity polymer gel, due to crosslinking

progressing, the mechanism and rate of reaction starts being controlled by viscosity. In

166

this stage of crosslink reactions, both macro-radical and macro-monomer diffusion can

be hindered, so as a result, the probability of propagation reaction decreases. This

difficulty in propagation reaction causes reduction in macro-monomer consumption rate.

This effect was shown with 1H-NMR which was run for swollen gel in CDCl3. This

result shows some unreacted acrylate groups are in the swollen gel. In Figure 4. 2 1H-

NMR result of swollen gel that was crosslinked with UV and post cured in oven in inert

atmosphere is shown. The peaks from 5.8 to 6.1 ppm are for unreacted acrylate protons

which prove all acrylate has not been consumed during the crosslinking process.

Figure 4. 2. 1H-NMR in CDCl3 of the swollen gel synthesized from the bis acrylate

PEG 2000.

This unreacted acrylate (chapter one, equation 1.32) [7] appears as either a

dangling chain in network or as an unreacted macro-monomer (both ends of bis acrylate

PEG are unreacted). The analogous situation in crosslinked in situ silsesquioxane PEG

was described and examined by DSC in chapter three, section 3.2.3.1.1. As mentioned

there the dangling chain can change the hydrogels mechanical and swelling properties

167

which can be seen in percentage of swelling and crystalline structures in DSC

measurement.

The other possible formation of dangling chains can be caused by very early

termination reaction which can be formed by coupling termination reaction (as was

discussed in chapter one, section 1.5.1) between macro-radical and radical initiator, as

shown in equation 4.1. . This type of dangling chain can be observed when very high

concentration of initiator is introduced. This is because when the population of initiator

radical is very high the probability of coupling termination reactions between shorter

oligomers and initiator radicals increases dramatically.

(4.1)

This phenomenon can be enhanced when polymer concentration increases,

because diffusion rate is very slow for macro-monomer and macro-radical, but diffusion

rate is faster for initiator due to molecule size difference.

To limit the amount of acrylate dangling chain, the concentration of bis acrylate

PEG in the starting solution needs to be lower, but polymer with low concentration can

lead to lower mechanical properties due to decreased number of entanglements [8-10] in

both polymer solution and network. Thus, polymer solution must be highly concentrated

during crosslink process to get reasonable high mechanical and damping properties.

These concentration effects were tested by DMTA in this study.

According to Pilař [10] the initial concentration of monomer can change the

swelling behavior and hydrogel properties due to the change in the number of

entanglements. This is because entanglements are permanently trapped in between two

crosslinking junctions. It is impossible to disentangle them during swelling or applying

168

mechanical force or shear. The initial concentration of bis acrylate PEG (as a macro

monomer) can affect the final network properties such as percentage of swelling and tan

δ due to the number of entanglements.

Figure 4. 3. DMTA results (tan δ and E” versus temperature) in bis acrylate PEG

6000 networks with 50% (wt/wt) polymer in methanol solution and 35% (wt/wt)

polymer in methanol solution.

In Figure 4. 3, DMTA results for dry networks formed from two different

concentrations of bis acrylate PEG6000 in methanol (50% and 35% wt/wt polymer to

solvent) are shown. The concentrations of initiator in these two batches are different, so

it can lead to differences in the rate of polymerization. However, this polymerization

rate difference effect was removed by higher irradiation and post cure time duration (as

mentioned in chapter two, section 2.4.3). In this experiment bis acrylate PEG 6000 was

used instead of bis acrylate PEG 2000, because in PEG 6000 the number of

entanglements (due to its greater chain length) is higher compared to PEG2000. When

169

polymer chains become highly entangled, chains become difficult to move. In other

words, polymer viscosity is related to the number of entanglements [11] where the

number of entanglements increases when the concentration of polymer solution rises.

Therefore, tan δ which is related to viscous part of viscoelastic material changes with

entanglements. This change in tan δ is obvious in Figure 4. 3, when concentration

increases, tan δ value increases. These tan δ results can be verified by loss modulus (E”)

to show whether the tan δ change is because the storage modulus (E’) drops or loss

modulus increases.

The other experiment which can show the effect of the number of permanent

entanglements on hydrogel properties is the swelling measurement at equilibrium in

water [10]. The results in PEG6000 hydrogels synthesized from 50% and 35% (wt/wt)

polymer precursor in methanol are shown in Figure 4. 4. The results show that the

samples formed with the higher concentration of polymer precursor in methanol swell

less in water. This probably arises because at higher concentration an increased number

of entanglements are formed which can restrict chain extension during swelling. In other

words, entanglements are a physical crosslink which decreases the percentage of

swelling at equilibrium.

For this reason, it was determined that the concentration in all similar polymer

solutions needed to be kept constant, but during degassing it was possible that the

concentration changed. The other important parameter is initiator concentration which

was kept constant to eliminate the effect of initiator on the kinetic chain length of

acrylate polymerization. A post-cure process (under inert atmosphere at 55 °C

overnight) was performed for all samples under nitrogen atmosphere to reduce

unreacted acrylate group concentration by further reaction between macro-radicals and

either macro-monomer (propagation) or another macro-radical (termination).

170

500

700

900

1100

1300

1500

1700

1900

35% PEG/MeOH 50% PEG/MeOH

% o

f Sw

ellin

g

Figure 4. 4. Percentage of swelling by water of bis acrylate PEG 6000 hydrogels

which were synthesized in 50% (wt/wt) polymer solution in methanol and 35%

(wt/wt) polymer solution in methanol.

4.2.4 Results and Discussion of Properties of Reinforced Networks

PEG-based networks in the dry state have both crystalline and amorphous

regions. However, in service, hydrogels are swollen in water (or any other swelling

agent) and as a result, crystalline structures can differ in dry networks compared to

swollen hydrogels. In this research, mechanical properties and silica-network interfacial

interactions were tested in dry networks to eliminate all other swollen hydrogel effects

on properties. This is because the swollen hydrogel properties can be affected by the

percentage of swelling. In other words, the swollen hydrogel properties can change with

the amount of swelling agent and it is difficult to maintain a constant degree of

hydration during temperature ramping experiments in DSC and DMTA.

171

4.2.4.1 Effect of Silica Percentage on Dry Reinforced Networks

Networks with different percentage of silica A300 (0%: PEG2000AS0, 2%:

PEG2000AS2, 10%: PEG2000AS10 and 20%: PEG2000AS20) were synthesized as

mentioned in chapter two, section 2.4.3. The samples were tested by DMTA from -90 to

50 °C with 2 °C/min. ramping at 5 Hz (chapter two, section 2.7.5).

Figure 4. 5. DMTA result (E’ versus temperature) in reinforced bis acrylate PEG

PEG2000 networks PEG2000AS0, PEG2000AS2, PEG2000AS10 and

PEG2000AS20.

As mentioned in chapter one, section 1.6, the percentage of reinforcing agent

changes the Young’s modulus (E’) of composites. This increase in modulus is obvious

in Figure 4. 5 below and above the crystal transition temperature. Below the crystal

transition temperature networks are reinforced with both silica and crystalline blocks.

The results (Figure 4. 5) show modulus in PEG2000AS20 is the highest over the large

172

range of temperature compared to all other reinforced samples. As a result, in this

research to study the effects of silica-PEG interface on reinforced samples, 20% silica

was used, based on the results in Figure 4. 5.

4.2.4.2 Effects of Hydrogen Bonding on tan δ

As mentioned in chapter one, section 1.7.1.1, at the glass transition temperature

the polymer backbone starts moving along several carbon atoms. The chain segments in

amorphous region start undergoing movement along the backbone chains.

Polymeric materials do not have a fixed glass transition temperature, this

temperature is under the influence of the flexibility of the chains, steric hindrance, size

and nature of the side groups attached to the backbone, symmetry in the structure,

crosslinking, molecular weight, degree of crystallinity, plasticizers, fillers and impurities

[11-13].

These different movements are shown in Figure 4. 6 (a, b and c). This means that

if the surface of silica has stronger interfacial interaction with PEG backbone such as

hydrogen bonding (chapter three, Figure 3. 9) [14], this effect may be detectable with

the glass transition temperature and also tan δ curve changes.

Figure 4. 6. Vibration and rotational movement of the polymer back bone a) below

Tg, b) above Tg in pure polymer and c) above Tg when polymer chain movement is

hindered with any interaction.

To check this interfacial interaction between PEG and silanols on the surface of

silica, DMTA was run for both dry networks PEG2000AS20 with A300 silica and

network PEG2000AS20 with calcined silica (PEG2000AS20C). During calcination

process (900 °C) neighboring silanols are condensed and water is released, the surface

173

of silica after this heat treatment process has fewer silanol groups that are single silanols

(chapter one, section 1.6.2.1 and equation 1.47).

When the number of silanols decreases interfacial interactions (hydrogen

bonding) drops, as a result, rotational movement at backbone (chapter one, sections

1.7.1.1 and 1.8.1.1) [12] can be different between network with A300 silica and network

with calcined-silica. The other possible effect is introduction of moisture into a network

through silica surface. This is because water molecules hydrogen bond with silanol.

When the number of silanol groups decreases, the number of physisorbed water

molecules drops. As a result, plasticization effect on the hydrogels is related to the

number of silanol groups on the surface of silica.

Calcination process in silica was followed by thermogravimetric analysis (TGA)

in Figure 4. 7. The results show a drop below 100 °C in both A300 silica and calcined-

silica, due to the loss of water. Further, this weight decrease in A300 silica is bigger than

the decrease in calcined-silica. This is because on the surface of A300 silica the number

of silanol groups is higher than on the surface of calcined-silica so the amount of

absorbed water is greater which is obvious in Figure 4. 7. From 140 to 840 °C weight

decrease in A300 silica is around 1.25% and in calcined-silica is less than 0.25%. In

TGA test from 140 to 840 °C the number of silanol groups in A300 silica dropped 2.76

per nm2 and in calcined-silica dropped 0.55 nm2. This result shows the number of silanol

groups decreased during calcination process. Based on TGA results, physisorbed water

in A300 silica is 2.9 g per 100 g A300 silica (2.9%) and in calcined-silica is 0.94 g per

100 g calcined-silica (0.94%).

Tan δ results in dry networks PEG2000AS20 and PEG2000AS20C demonstrate

some differences in both α-transition temperature and α’-transition temperature. (These

both were discussed in chapter one, section 1.8, in dynamic mechanical analysis

section).

174

Figure 4. 7. Thermogravimetric analysis results for A300 silica and calcined-silica.

Figure 4. 8. Tan δ curves in dry networks PEG2000AS20 and PEG2000AS20C

showing the effect of calcination of silica on the α’-transition and α-transition.

175

The shift in α-transition temperatures in networks PEG2000AS20 compared to

networks PEG2000AS20C (Figure 4. 8) can be because of moisture that was introduced

to networks PEG2000AS20 which acts as a plasticizer or the effect of silanol group on

network properties.

As mentioned in dynamic mechanical analysis section in chapter 1, section 1.8,

the α’-transition is a rotational movement in backbone that starts from one side of

polymer crystal (defects [15]) and moves along it until it leaves this crystal cell [13, 15-

18]. This movement is initiated from interface of amorphous and crystalline regions,

essentially from defects or confined chains [18].

It is possible these defects appear on the interface of PEG crystalline region and

silica surface. The silica particle can start crystallization as a nucleation agent and

crystalline blocks grow from this point, so the particle is attached or very close to a

crystalline region (as shown in chapter three, Figure 3. 47 c). Rotational movement that

starts from this point in the amorphous region is then transferred to the crystalline

region. This obvious interfacial interaction may cause a shift in this transition

temperature. Both of these samples were tested by DSC in step crystallization method

(Figure 4. 9). In networks PEG2000AS20C, two overlapping peaks appear and one of

them (the smaller one) is around the crystal transition temperature in PEG2000AS20 and

the other one is at a higher temperature. Although the DSC and DMTA techniques probe

at different frequencies, and specific movements in crystalline regions cannot be

detected by DSC, a temperature shift in the DSC was observed when the silica was

calcined.

These results may have another explanation, but they clearly show that the level

of silanol on the surface of silica can have significant effects on dry network properties.

Better understanding of the interaction between a silica surface with different number of

silanol groups and PEG networks needs further investigation and application of different

analytical techniques.

176

Figure 4. 9. DSC results with step crystallization method in PEG2000AS20 and

PEG2000AS20C showing the effect of calcination.

4.2.4.3 Effects of Different Surface Chemistry of Silica on Reinforced PEG

Networks

Interfacial interaction between filler and reinforced polymer plays an important

role in better filler dispersion [19, 20] and higher mechanical properties in composites.

Dispersion takes place during suspension in methanol and a sonication process (as

mentioned in chapter two, section 2.4.3). This achieves good dispersion without any

shear force which can cause change in polydispersity index (PDI) of polymer through

shear-induced chain scission.

The storage modulus, E’ is a parameter that can be measured with DMTA. As

shown in Figure 4. 10, E’ rises when filler is introduced to reinforce networks. In the

range of temperature (15 to 45 °C) where the crystal transitions take place it is obvious

177

the effect of silica and the chemistry of silica surface have an effect on the modulus. The

modulus decrease during the crystal transition in PEG2000AS0 (non-reinforced

PEG2000 network) is higher than modulus decrease in all PEG2000 networks reinforced

with silica nano-particles with different surface treatments (PEG2000AS20,

PEG2000AP-S20 and PEG2000AV-S20 (chapter two, Table 2. 4)) in the same

temperature range. In reinforced networks above the crystal transition temperature

(where the reinforcing effects of crystalline regions are eliminated) the modulus

decrease is lower compared to non-reinforced networks due to influence of silica with

different surface chemistry. The transition in PEG2000AS20 is different from other two

samples PEG2000AP-S20 and PEG2000AV-S20. Tan δ is sensitive to interfacial

interaction between different phases in polymer blends or between filler and polymer

bulk in reinforced polymers [13].

As mentioned earlier, interfacial interaction can be altered by changing filler

surface chemistry. The surface of silica can change to totally hydrophobic by

functionalizing silica with trimethoxy(propyl)silane. Alternatively the surface of silica

may be made reactive by using triethoxyvinylsilane to react with the acrylate group in

bis acrylate PEG precursor during network UV curing process (in PEG2000AV-S20).

The maximum of tan δ in α-transition temperatures show shifts to both lower

(PEG2000AS20) and higher (PEG2000AP-S20 and PEG2000AV-S20) temperatures

compared to α-transition temperature in PEG2000AS0, and the highest peak intensity

appears in PEG2000AS0. These shift and intensity changes occur due to hindered

rotational movement in backbone (chapter 1, section 1.8.1.1) which is started at α-

transition.

The only result that is not matched with this hindering effect appears in

PEG2000AS20. In this network a plasticizing effect can be observed rather than a

“hindered movement” effect. The α-transition temperature shift to higher temperature

and lower intensity of tan δ in reinforced networks shows there is interfacial interaction

between silica surface and polymer bulk which can be altered with silica surface

chemistry, as was discussed in section 4.2.4.2. When the silanol group on the surface of

silica changes to propyl or vinyl group, silica surface properties change from

178

hydrophilic to hydrophobic and this can change the polymer properties. According to

Schadler [21] and Liu [22] the large polymer-filler interface in nano-composite

materials creates a significantly larger fraction of interfacial polymer which has different

properties from the bulk [21-23]. The portion of this interfacial polymer (or interphase)

can change with either percentage or aspect ratio of filler.

Figure 4. 10. DMTA results (E’ and tan δ) in PEG2000AS0, PEG2000AS20,

PEG2000AP-S20 and PEG2000AV-S20.

In samples PEG2000AP-S20 and PEG2000AV-S20, hydrophobic barrier

between polymer chains and silica means that it will be very difficult for the polymer

chain to build up hydrogen bonding, although it is possible that vinyl-silica particle can

make covalent bond with bis acrylate PEG2000 precursor through radical reaction

between vinyl and acrylate groups in crosslinked part of networks. However, the α-

transition temperature in tan δ curves shift to higher temperature in both samples

PEG2000AP-S20 and PEG2000AV-S20 compared to the α-transition temperature shift

179

in PEG2000AS20. The reason for these temperature shifts is unknown, because it has

been believed that hydrogen bonding dominates interactions between networks and

A300 silica, so as a result, the shift to the highest temperature would be expected to

appear in PEG2000AS20. These types of interaction need more investigation to

understand why this shift in the α-transition occurs toward lower temperature. As

mentioned in section 4.2.4.2, it is possible silanol groups carry water molecules into

network though hydrogen bonding and this causes plasticization in interfacial region.

Figure 4. 11. DMTA in multi frequency (5, 10, 25 and 50 Hz) mode of experiment

in PEG2000AS20.

The α’-transition temperature shifts show the other interesting result which has

been observed in tan δ curve in PEG networks. As mentioned in chapter 1, section 1.8,

all transitions measured in DMTA and DSC tests are second order transition except

melting which is independent of both rate of heating and frequency (ie. a first order

transition). The order of transitions can be obtained by running DMTA in multi-

180

frequency mode (applying four frequencies simultaneously). The results are shown in

figure 4.13 and it may be seen that tan δ in the α-transition shows shift to higher

temperature with higher frequency. This result can be confirmed with E’ shift at Tg and

a very similar shift can be observed in the α’-transition with frequency as well.

However, E’ at second drop (equal to melting in thermoplastic polymers) does not

undergo any shift over a range of temperature from 20 to 40 °C. This experiment

clearly proves the peak appearing after the α-transition is a real α’-transition and it is not

a pre-melting artifact.

The α’-transition results in Figure 4. 10 show different temperature shifts in

different networks. The highest temperature in the α’-transition belongs to the

unreinforced network PEG2000AS0. In PEG2000AS20, the α’-transition temperature is

at the lowest temperature. The α’-transition temperatures in PEG2000AP-S20 and

PEG2000AV-S20 were observed at very close temperatures but the transition in the

sample PEG2000AV-S20 was a little higher than the transition in the sample

PEG2000AP-S20. As was discussed in chapter one, section 1.8, the α’-transition

temperature depends on size and structure of crystalline region as well as defects on the

surface of crystalline regions. These results show effects of chemistry of silica surface

on the crystalline structures. The crystalline structures change with silica particles which

have a nucleation effect during crystallite formation. When the surface of particles has

better interaction with polymer chains, they can act as an active nucleation agent [24].

All these samples were analyzed by DSC in step crystallization method (Figure

4. 12). In these results the crystal transition temperature increased on adding 20% silica

(PEG2000AS20, PEG2000AP-S20 and PEG2000AV-S20) compared to PEG2000AS0.

181

Figure 4. 12. DSC results in PEG2000 networks with different types of silica

(PEG2000AS20, PEG2000AP-S20 and PEG2000AV-S20) and without silica

(PEG2000AS0).

As shown in Figure 4. 12, all reinforced and non reinforced bis acrylate PEG

2000 networks were examined by DSC (step crystallization method). The crystal

transition temperature in PEG2000AP-S20 is the highest of all the samples. The

transition temperature at PEG2000AS20 is slightly lower than PEG2000AP-S20. The

results in PEG2000AV-S20 and PEG2000AS0 are very close. In PEG2000AS0 two

overlapping peaks were observed which suggests two different crystalline structures.

The peak at higher temperature in sample PEG2000AS0 is very close to the crystal

transition temperature in PEG2000AV-S20. Silica surface chemistry as shown in Figure

4. 14 changes the crystal transition temperatures. This is because the nucleation process

during crystallization can be more effective when more interactions occur between

polymer chain and the surface of particle. For an unknown reason this interaction

between propyl groups on the surface of silica is relatively intense, however propyl

182

makes silica surface more hydrophobic and PEG chain is hydrophilic. The endothermic

peaks in reinforced samples appeared as a single peak compared to PEG2000AS0 with

double overlap peaks. This shows thermodynamically silica with the different surface

chemistry can control the crystalline structures in spite of crosslinking network.

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

PEG2000AS0 PEG2000AS20 PEG2000AP-S20 PEG2000AV-S20

% o

f Sol

Fra

ctio

n

Figure 4. 13. Percentage of sol fraction in bis acrylate PEG 2000 networks with and

without different types of silica (PEG2000AS0, PEG2000AS20, PEG2000AP-S20

and PEG2000AV-S20).

The crosslinking effect is obvious in PEG2000AS0. All these results prove silica and

silica surface chemistry have effects on crystalline structures in bis acrylate PEG2000

networks.

As mentioned in chapter 3, all silane groups were reacted and changed to three

dimensional networks in networks which were synthesized with sol-gel method. This

was confirmed with 29Si NMR that no dangling chain is in networks, but in acrylate

method for network formation, 1H NMR shows some unreacted acrylate group in

network (Figure 4. 2) which acts as dangling chain or free chain. As was discussed in

183

chapter three, section 3.2.3.1.1, dangling chain can change network structures and the

percentage of swelling. This is because in acrylate polymerization, unreacted acrylate

groups remain in networks (as discussed in section 4.2.3).

To determine the structural stability of hydrogels, the % sol fraction of the

different hydrogels was measured. The results are given in Figure 4. 13 which shows the

minimum sol fraction was in sample PEG2000AV-S20 and importantly this minimum

result is higher than all sol fraction results which were examined in sol-gel method of

network synthesis (in chapter 3). These results in Figure 4. 13 compared to sol fraction

results in the sol-gel reaction method of network synthesis indicate that unreacted chains

in networks that were synthesized by the acrylate method have affected the network

0

50

100

150

200

250

300

350

PEG2000AS0 PEG2000AS20 PEG2000AP-S20 PEG2000AV-S20

% o

f Sw

ellin

g

Figure 4. 14. Percentage of swelling in bis acrylate PEG 2000 hydrogels with and

without different types of silica (PEG2000AS0, PEG2000AS20, PEG2000AP-S20

and PEG2000AV-S20) in water at equilibrium.

properties. In addition, these results are supported by the detection of unreacted acrylate

groups by 1H NMR Figure 4. 2.

184

In Figure 4. 14 are shown the percentage of swelling of bis acrylate PEG 2000

hydrogels (PEG2000AS0, PEG2000AS20, PEG2000AP-S20 and PEG2000AV-S20) in

water at equilibrium. The highest swelling percentage is in hydrogel PEG2000AS0. This

is because this hydrogel is not reinforced, as a result, deformation in hydrogel develops

less elastic force during swelling compared to other reinforced hydrogels. Swelling

measurement calculation in all reinforced hydrogels was corrected for the amount of

silica.

4.2.4.4 Effect of Different Length of Silica Surface Modifier on Reinforced PEG

Networks

As mentioned in the previous section, the chemistry of a silica surface can

change the interactions between surface of silica and PEG networks. The length of the

modifier chains on the surface of silica is another factor that can be considered. When

the type of modifiers are similar and the length of chains are different (in this section all

are PEO with different chain lengths), the interaction between silica surface and

networks be different (Figure 4. 15). For functionalizing silica surface with different

length of PEO, in the first step, triethoxy silyl propyl urethane-PEO needs to be

synthesized (chapter two, section 2.2.2).

Figure 4. 15. Interaction between networks and silica particles with short (a) and

long (b) chains on the surface.

The synthesis, characterization and silanization reaction were described in

chapter two, section 2.1.1 and chapter three, section 3.2.2.2 and equation 3.1.

Functionalized silica was characterized with 29Si solid state NMR and TGA (chapter

185

three, section 3.2.2.2). As mentioned in chapter one, section 1.7.1.2, a polymer chain,

for packing in a crystallite, needs to have a minimum length and order in short (tacticity,

both syndiotactic and isotactic) and long (copolymer and conventional crosslinking)

scales. PEG meets all conditions to be packed in a crystallite when it has sufficient

length and other conditions such as temperature are totally satisfied for packing (as

mentioned in chapter one, section 1.7.1.2). Polymer chains with lower molecular weight

stay in the amorphous region. This is the reason silica surface was modified with several

different silanes of different molecular weight.

This difference in PEG chain length can alter interaction between silica particles

from amorphous region interactions to amorphous and crystalline region interactions

which causes tension and force transfer. Tension transfer in amorphous region can also

change with the length of chain due to dependency of interaction intensity (tension and

force transfer) with number of entanglements. The number of entanglements is a

function of chain length [25]. On the other hand, when the length of chain is long

enough, the chain has a chance to be packed in one or several crystallites which can

transfer and distribute tension through crystalline regions to the surface of silica. These

effects either on amorphous or on crystalline regions can be tested with DMTA, because

relaxation of the attached PEO chain can be different from the chain which is bonded to

networks and interaction between these two types of PEG chains (in network and on the

surface of silica) can appear as shift or change in both the α and α’-transition peaks.

These effects on samples PEG2000PEO20-S20 and PEG2000PEO-S20 and

PEG2000AS0 were studied with DMTA as shown in Figure 4. 16.

The results show distinguishing changes in all E’ and tan δ curves versus

temperature which clearly indicate interaction (tension transfer and friction through

entanglements between PEO and PEG networks) between different chain length on the

surface of silica and networks. In plots of E’ changes versus temperature, the effect of

silica particles on networks is very obvious when PEG2000PEO20-S20 and

PEG2000PEO-S20 (both reinforced) are compared with PEG2000AS0 (non-reinforced),

with the modulus in PEG2000AS0 being lower than both PEG2000PEO20-S20 and

PEG2000PEO-S20 regardless of the size of PEO chain on the surface of silica.

186

Figure 4. 16. E’ and tan δ versus temperature in bis acrylate PEG 2000 networks

with PEO-silica (PEG2000PEO-S20), PEO2000 DCM2-silica (PEG2000PEO20-

S20) and no silica (PEG2000AS0).

E’ curves show the effect of different types of silica in networks on modulus

over a wide range of temperature (from -90 to 50 °C). At very low temperature (below -

60 °C) the differences between samples PEG2000PEO20-S20 (molecular weight of

PEO is 2000 Da) and PEG2000PEO-S20 (molecular weight of PEO is 500 Da) are very

low, then, above -60 °C, divergence starts between the curves for these networks. This is

because the chain length attached on silica surface in PEG2000PEO-S20 is too short to

be able to be packed in a crystallite with network chains. When the temperature

approaches to the α-transition the shorter chains in amorphous regions undergo change

in mechanical properties and modulus (decrease in E’). However, crystalline regions can

stay without any changes in properties and structures until near the α’-transition

temperature. The results in Figure 4. 16 demonstrate the effects of chain length on the

187

mechanical properties. E’ curve over range of temperature from -50 to 20 °C in

PEG2000PEO20-S20 has a lower slope of E’ decrease compared to PEG2000PEO-S20

(Figure 4. 16) reflecting the effect of PEO length on E’. In other words, in

PEG2000PEO20-S20, the PEO2000 chains can be crystallized with PEG chains in

network (co-crystallization), as a result, PEO2000-silica enhances network properties

more than PEO-silica with a lower chain length. This effect will also be discussed later

in this section with tan δ results. In other words, silica particles and crystalline regions

were connected to each other by long chains which started from surface of silica

particles and passed through one or several crystallites (based on switch board and chain

folded model in semi-crystalline polymer) and some portion of these PEO2000 chains

stayed in amorphous region as tie chains. As mentioned in chapter 3, section 3.2.3.1.1,

concerning the effect of dangling chains on crystallization process in networks, the PEO

2000 Da chains on the surface of silica have a higher ability to be packed compared to

chain segments which are confined between two crosslink junctions.

The second plunge in the E’ curves (from 25 to 40 °C) can be observed when

temperature reaches the beginning of the crystal transition temperature. In this

temperature range those crystalline regions with the smallest defect structures start

undergoing the crystalline to amorphous transition. With an increase of temperature,

crystalline regions with bigger size or fewer defects in structures are added to

amorphous fraction where a higher decrease in E’ curves occurs. This process continues

until all crystalline regions become amorphous regions. This decrease in E’ occurs

around the same temperature in all networks as shown in Figure 4. 16. However, the

decrease at E’ in this range of temperature (from 25 to 40 °C) in PEG2000AS0 is greater

than from the other two networks. This is because in fully amorphous networks the

effects of silica and crosslink are retained but the effect of the crystalline region is

totally removed. Although all crystalline regions change to amorphous regions, E’ in

reinforced PEG2000PEO20-S20 with the same filler loading is higher than E’ in both

PEG2000AS0 and PEG2000PEO-S20. Earlier in this discussion, the interaction between

crystalline structures and silica particles through tie chains was explained. Here, above

the crystal transition temperatures, again the same trend appears, E’ in PEG2000PEO20-

S20 is higher than both PEG2000AS0 and PEG2000PEO-S20. This is because of

188

tension transfer from bulk of networks to the silica particles related to interaction

strength between network segments and PEO which is attached to silica. According to

Foteinopoulou [25] the number of entanglements is a function of polymer chain length.

According to Pizzi [26], in PEG based networks the minimum critical entanglement is

around 900 Da (for PEG/ water, 70% wt./wt.). This means when PEO chain length

(attached to silica) increases from 500 Da to 2000 Da, the number of entanglement and

interaction increase which causes a rise in E’ (Figure 4. 16 and Figure 4. 15).

At the α’-transition temperature, the rotational movement of chains in crystalline

regions start. As mentioned in chapter 1 section 1.8, this movement initiates from one

side of crystallite and moves along this crystallite. Both processes have an associated

activation energy which is related to the size of crystallite and number of defects on the

surface of it. As shown in Figure 4. 16, the first change in tan δ appears in the α-

transition which is related to the glass transition temperature and the second peak is the

α’-transition. The α-transitions in all networks show changes in both the maximum

intensity and maximum peak positions. In PEG2000PEO-S20 a decrease in intensity of

the peak maximum in the α-transition was observed compared to PEG2000AS0. In

PEG2000PEO20-S20, intensity in the α-transition also decreases compared to both

PEG2000AS0 and PEG2000PEO-S20. These intensity drops in reinforced networks

with different silica surface structures show the effects of silica and the length of PEO

chains on the surface of silica in amorphous regions. The segments of PEO (several

repeating units) which are chemically attached to the surface of silica remain in the

amorphous region. These segments of PEO can change the properties of amorphous

regions which are clearly shown in Figure 4. 16. In sample PEG2000PEO-S20 the

chains attached to silica (PEO with 500 Da) are stretched in amorphous regions which

can change the properties such as flexibility in these regions due to interaction between

PEO hanging chains and PEG2000 network segments. The network segments in

amorphous regions are mostly the closest segments to the crosslinks part of networks

because crystallization process in this part of chains is suppressed due to chain

irregularity and low flexibility. Interactions between these crosslinked segments of

networks and PEO (500Da) chains on the surface of silica causes a decrease in intensity

of tan δ in the α-transition (retarding rotational movements around Tg). When PEO chain

189

length increases from 500 Da to 2000 Da the interactions change from only amorphous

interactions in PEO500 to amorphous and crystalline region interactions for PEO2000

which has been attached to the surface of silica. As a result, the α-transition movement

is retarded by both silica particles and PEO2000 dangling chains which are packed in

crystalline regions [11, 13]. The effects of dangling chains on crystallinity can be

verified by step crystallization DSC in Figure 4. 17, which will be discussed later in this

section.

In the α’-transition, the effects of silica with different surface chemistry can be

detected with both peak shapes and temperature shifts. In Figure 4. 16 tan δ is shown

versus temperature in all PEG2000AS0, PEG2000PEO-S20 and PEG2000PEO20-S20.

The α’-transition in PEG2000AS0 appears at the highest temperature with the lowest

intensity compared to two of the reinforced networks. The α’-transition in

PEG2000PEO-S20 appears at the lowest temperature among all three networks, and the

peak is very broad which shows the shorter chain can change the crystalline structures in

terms of size and defects, although these shorter chains (around 500 Da) cannot undergo

a co-crystallization process with network segments. The α’-transition peak in

PEG2000PEO20-S20 shifts to higher temperature and becomes narrower compared to

PEG2000PEO-S20, and the peak appears at lower temperature and becomes broader

compared to PEG2000AS0. The intensity of the α’-transition peak in PEG2000PEO20-

S20 is highest among all three networks. These results show PEO2000 chains are able to

undergo co-crystallization with PEG network segments as dangling chains. This co-

crystallization can cause a higher number of sites on the surface of crystalline regions

which can be initiator for rotational movement with lower activation energy for the α’-

transition in crystalline region.

As shown in Figure 4. 17, the crystalline structures in all three networks can be

examined with DSC step crystallization. In PEG2000PEO20-S20, the crystal transition

temperature peak is the sharpest and appears in the highest temperature compared to

samples PEG2000PEO-S20 and PEG2000AS0. The crystal transition temperature in

PEG2000AS0 has two overlapping peaks where the higher peak is very close to the

crystal transition temperature in PEG2000PEO20-S20. These results show that

crystalline structures in PEG2000PEO20-S20 are very similar to crystalline structures in

190

PEG2000AS0 which has a higher transition temperature. The crystal transition

temperature in PEG2000PEO-S20 also has two overlapping peaks where each peak is

slightly lower than the equivalent peak in PEG2000AS0. The significant difference in

the endothermic peaks between PEG2000AS0 and PEG2000PEO-S20 is the shoulder in

PEG2000PEO-S20 which shows different crystalline structures compared to the other

two networks.

Figure 4. 17. Step crystallization DSC for networks PEG2000AS0, PEG2000PEO-

S20 and PEG2000PEO20-S20.

In Figure 4. 18, percentages of swelling of hydrogels PEG2000AS0,

PEG2000PEO-S20 and PEG2000PEO20-S20 in water at equilibrium are shown. The

method of calculation has been corrected for the effect of silica on swelling percentage.

The swelling percentages for reinforced hydrogels PEG2000PEO-S20 and

PEG2000PEO20-S20 are very close, but slightly lower when compared to

191

PEG2000AS0. This is because the modulus of reinforced hydrogels increase compared

to non-reinforced hydrogel (Figure 4. 16) so hindering the swelling.

Figure 4. 10 and Figure 4. 14 results also showed that when different types of

silica were added, modulus increased but percentages of swelling decreased compared to

non-reinforced hydrogel.

0

50

100

150

200

250

300

350

PEG2000AS0 PEG2000PEO-S20 PEG2000PEO20-S20

% o

f Sw

ellin

g

Figure 4. 18. Percentage of swelling of hydrogels PEG2000AS0, PEG2000PEO-S20

and PEG2000PEO20-S20 in water at equilibrium.

The other technique to study crystalline structures is XRD (X-ray Diffraction). In

this method, crystalline structures in semi-crystalline materials can be investigated based

on d-spacings and intensity of diffraction versus 2θ (Bragg’s law). In this project

reinforced networks with different types of silica were examined with XRD and results

are shown in Figure 4. 19. However, the results of crystalline structures which were

obtained by this technique are not very accurate due to temperature effect. This is

because XRD equipment is operated at room temperature, and structural changes occur

around this temperature. As shown in Figure 4. 19 all PEG2000 networks show weak

intensity compared to that of PEG2000 [27].

192

0

10000

20000

30000

40000

50000

60000

0 10 20 30 40 50 60 70Angle 2θ

Int.

PEG2000 PEG2000AS20 PEG2000AV-S20PEG2000SWS0 PEG2000APEO-S20 PEG2000APEO20-S20PEG2000AS20C

Figure 4. 19. XRD intensity versus angle (2θ) in neat PEG, PEG2000SWS0,

PEG2000AS20, PEG2000AS20C, PEG2000AV-S20, PEG2000APEO-S20 and

PEG2000APEO20-S20.

4.2.4.5 Tensile Test on Reinforced Networks

For testing mechanical properties and interfacial effects of networks, tensile

testing was initially done in extension mode on samples that were absolutely dried to

avoid plasticization effects. The samples were in a bar shape and prepared by UV

irradiation in a glass mould. All samples were dried in the vacuum oven. However, all

samples suffered brittle failure at the tensile grips due to high crystallinity of samples.

This means this method is not applicable for these reinforced networks.

The other method used is a wet compression test. In this method, hydrogels reach

equilibrium in water then compression test is run on swollen samples [28, 29]. In this

method, the test result highly depends on the percentage of swelling. When two

hydrogels with similar crosslink density are swollen in water, the one which has the

higher swelling percentage, has the lower strength. According to Haraguchi, the ultimate

193

mechanical properties are affected by water content [30]. This is probably because

chains between two crosslinking junctions in higher swollen hydrogel reach closer to

carbon-carbon ultimate bond strain (Figure 4. 20 b) compared to hydrogel with lower

swelling percentage (Figure 4. 20 a). As a result, this method of tensile experiment

depends on level of water absorption.

Figure 4. 20. a) dry network, b) swollen hydrogel structures.

The results of compression test in swollen hydrogels at equilibrium in water (the

swelling percentages at equilibrium were presented in Figure 4. 14 and Figure 4. 18) are

shown in Figure 4. 21 and Table 4. 1. The results show all reinforced hydrogels at

equilibrium have higher strength compared to PEG2000AS0 (un-reinforced hydrogel).

Although strength in reinforced hydrogel is controlled by both crosslinking and

filler, these results suggest that samples with 20% filler loading have the dominant effect

on strength compa red to crosslinking.

194

Figure 4. 21. Compression test in swollen hydrogels (PEG2000AS0, PEG2000AS20,

PEG2000AV-S20, PEG2000AP-S20, PEG2000APEO-S20 and PEG2000APEO20-

S20) in water at equilibrium points (5 mm/min.).

195

Table 4. 1. Strength and Strain at Break in Swollen Hydrogels (PEG2000AS0,

PEG2000AS20, PEG2000AV-S20, PEG2000AP-S20, PEG2000APEO-S20 and

PEG2000APEO20-S20).

Strength (N/mm2) Strain (%)

PEG2000AS0 0.1136± 0.06 55.8± 6

PEG2000AS20 0.481 ± 0.06 50 ± 9

PEG2000AV-S20 0.545 ± 0.09 51 ± 9

PEG2000AP-S20 0.525 ± 0.062 63 ± 6

PEG2000APEO-S20 0.557 ± 0.091 49 ± 5.5

PEG2000APEO20-S20 0.852 ± 0.11 51 ± 4.5

4.3 Summary

In this chapter, research has shown the effect of silica reinforcement on thermal

and mechanical properties of networks that were formed through UV-induced radical

crosslinking by exposure of bis acrylate PEG precursor with or without silica with

different surface chemistry. The DMTA results have shown modulus changes of dry

reinforced networks over a wide range of temperature and the interfacial interaction

between dry network and silica with different surface chemistry has been measured. The

storage modulus, E’, in DMTA shows an increase with a rise in the percentage of silica

(A300) from 0% to 20%. The other technique that has been employed is step

crystallization DSC to study change in the crystal transition temperature in both

reinforced and non-reinforced networks. The percentage of swelling at equilibrium in

water has also been used probe network structures.

The α-transition in a reinforced network with A300 silica was shifted to lower

temperature compared to the non-reinforced network. This is due to possible water

plasticization effect which occurs with silica particles through hydrogen bonding. This

effect was explained by removing the water-silica hydrogen bonding via a calcination

process.

196

The investigation of the effect of different silica surface chemistry on mechanical

properties of network has been performed. The α-transition temperature shifts in

reinforced network with different types of silica showing the effect of interactions

between networks and treated silica. This was caused by the hindering effect on the

polymer rotational motion. The α’-transition temperature in all reinforced networks

shifted to lower temperatures compared to the α’-transition temperature in the network

without reinforcement. However, the intensity of the α’-transition peaks in reinforced

networks were higher than the peak in the PEG networks without silica. These

differences illustrated the effects of silica and surface chemistry on the network

structures. The effects on the crystalline transition temperatures were tested with DSC

which showed the differences between reinforced networks due to the nucleation effect

of silica with different surface chemistry.

The effects of PEO chain length of silica modifier on the reinforced networks

have been investigated. The α’-transition shifts in temperature and changes in intensity

and breadth of the peaks showed the effects of chain length of the modifier on the

networks. As discussed in this chapter, the interactions in both amorphous and

crystalline regions such as entanglement and co-crystallization caused these changes and

shifts. The effects of types and length of surface modifier (different silanes) on the

crystalline regions have been seen in DSC results which agree with DMTA outcomes.

The gel 1H NMR showed some acrylate groups are present in the cured network.

These acrylate groups can appear as either dangling or unreacted chains in the network

which can change the networks properties (as discussed in previous chapter in dangling

chain section). Compression test results on swollen hydrogels at equilibrium in water

showed the strength in all reinforced hydrogels were higher than un-reinforced hydrogel.

These improved mechanical results showed silica is an effective reinforcement agent in

swollen hydrogels.

197

Reference:

1. Poovarodom, S., Hosseinpour, D. and Berg, J. C., Effect of Particle Aggregation on the Mechanical Properties of a Reinforced Organic-Inorganic Hybrid Sol-Gel Composite. Ind. Eng. Chem. Res., 2008. 47(8): p. 2623-2629.

2. Gojny, F.H., Wichmann, M. H., Fiedler, B. and Schult, K., Influence of Different Carbon nanotubes on the Mechanical Properties of Epoxy Matrix Composites – A Comparative Study. Compos. Sci. Technol., 2005. 65: p. 2300–2313.

3. Fu, S.Y., Feng, X. Q., Lauke, B. and Mai, Y. W., Effects of Particle Size, Particle/matrix Interface Adhesion and Particle Loading on Mechanical Properties of Particulate–polymer Composites. Composites: Part B, 2008. 39: p. 933-961.

4. Cruise, G.M., Hegre, O. D., Scharp, D. S. and Hubbell, J. A., A Sensitivity Study of the Key Parameters in the Interfacial Photopolymerization of Poly(ethylene glycol) Diacrylate upon Porcine Islets. Biotechnol. Bioeng., 1998. 57(6): p. 655-665.

5. Odian, G., Principales of Polymerization. Fourth ed. 2004, Hoboken: John Wiley & Sons, Inc.


7. Moad, G., Solomon, D., H., The Chemistry of Radical Polymerization. Second ed. 2006, Amsterdam: Elsevier.

8. Colby, R.H., Effects of Concentration and Thermodynamic Interaction on the Viscoelastic Properties of Polymer Solutions. Macromolecules, 1991. 24: p. 3873-3882.

9. Colby, R.H., Rubinstein, M., Chain Entanglement in Polymer Melts and Solutions. Macromolecules, 1992. 25: p. 996-998.

10. Pilar, J., Kríz, J., Meissner, B., Kadlec, P. and Prádný, M., Effect of Structure of HEMA-DEGMA Hydrogel Matrix on Diffusion Coefficients of PEG Tracers. Variation of Hydrogel Crosslink Density by Change of Polymer Concentration. Polymer, 2009. 50(19): p. 4543-4551.

11. Nielsen, L.E., Landel, R. F., Mechanical Properties of Polymers and Composites. 2nd ed. 1994, New York: Marcel dekker, Inc.

12. Halley, P.J., George, G. A., Chemorheology of Polymers: From Fundamental Principles to Reactive Processing. 2009, New York: Cambridge University Press.


14. Derosa, R.L., Trapasso, J. A., Poly(ethylene glycol) Interactions with Alumina and Silica Powders Determined Via DRIFT. J. Mater. Sci., 2002. 37: p. 1079-1082.

15. Boyd, R.H., Relaxation Processes in Crystalline Polymers: Molecular Interpretation - a Review. Polymer, 1985. 26: p. 1123-1133.

16. Menard, K.P., Dynamic Mechanical Analysis. A Practical Introduction. 1999, Boca Raton: CRC Press.

198

17. Simon, L.C., De Souza, R. F., Soares, J. B. P. and Mauler, R. S., Effect of Molecular Structure on Dynamic Mechanical Properties of Polyethylene Obtained with Nickel–diimine Catalysts. Polymer, 2001. 42: p. 4885-4892.

18. Rault, J., The αC Transition in Semicrystalline Polymers: A New Look at Crystallization Deformation and Aging Process. Polym. Rev., 1997. 37(2): p. 335-387.

19. Hanumantha Rao, K., K.S.E. Forssberg, and W. Forsling, Interfacial Interactions and Mechanical Properties of Mineral Filled Polymer Composites: Wollastonite in PMMA Polymer Matrix. Colloids Surf., A:, 1998. 133(1-2): p. 107-117.

20. Balazs, A.C., T. Emrick, and T.P. Russell, Nanoparticle Polymer Composites: Where Two Small Worlds Meet. Science, 2006. 314: p. 1107-1110.

21. Schadler, L.S., Brinson, L. C. and Sawyer, W. G., Polymer Nanocomposites: A Small Part of the Story. JOM Journal of the Minerals, Metals and Materials Society, 2007. 59(3): p. 53-60.

22. Liu, Y.J., Nishimura, N., Otani, Y. and Mokashi, V., A Boundary Element Method for the Analysis of CNT/Polymer Composites with a Cohesive Interface Model Based on Molecular Dynamics. Eng. Anal. Boundary Elem., 2008. 32: p. 299–308.

23. Sen, S., Thomin, J. D., Kumar, S. K. and Keblinski, P., Molecular Underpinnings of the Mechanical Reinforcement in Polymer Nanocomposites. Macromolecules, 2007. 40: p. 4059-4067.


25. Foteinopoulou, K., Karayiannis, N. C. and Mavrantzas, V. G., Primitive Path Identification and Entanglement Statistics in Polymer Melts: Results from Direct Topological Analysis on Atomistic Polyethylene Models. Macromolecules, 2006. 39: p. 4207-4216.

26. Pizzi, A., Garcia, R. and Deglise, X., Thermomechanical Analysis of Entanglement Networks: Correlation of Some Calculated and Experimental Parameters. J. Appl. Polym. Sci., 1998. 67: p. 1673–1678.

27. Chaiko, D.J., New Poly(ethylene oxide)-Clay Composites. Chem. Mater, 2003. 15: p. 1105-1110.

28. Huang, T., Xu, H., Jiao, K., Zhu, L., Brown, H. and Wang, H., A Novel Hydrogel with High Mechanical Strength: A Macromolecular Microsphere Composite Hydrogel. Adv. Mater, 2007. 19: p. 1622–1626.

29. Stammen, J.A., Williams, S., Ku, D. N. and Guldberg, R. E., Mechanical Properties of a Novel PVA Hydrogel in Shear and Unconfined Compression. Biomaterials, 2001. 22: p. 799-806.

30. Haraguchi, K., Farnworth, R., Ohbayashi, A. and Takehisa, T., Compositional Effects on Mechanical Properties of Nanocomposite Hydrogels Composed of Poly(N,N-dimethylacrylamide) and Clay. Macromolecules, 2003. 36: p. 5732-5741.

199

Chapter 5: Sorption and Desorption of Silicone

Fluids by PEG Gels

5.1 Introduction

As mentioned in chapter one section 1.2, silicone therapy is one of the successful

scar remediation methods. However, the treatment needs a very long period of

application which can bring difficulty in patient compliance to achieve the benefit of the

therapy. In this chapter swelling and deswelling of PEG-based networks with an active

candidate amphiphilic rake silicone copolymer will be discussed. This oligomeric

siloxane fluid has been shown to down-regulate collagen production and so provide a

potential therapy for hypertrophic scars. Introduction of the rake silicone copolymer was

based on diffusion. The fully dry PEG network was immersed into pure rake silicone

copolymer, as mentioned in chapter two, section 2.6, and the weight was recorded at

equilibrium (ie no further weight increase with time).

The amount of swelling agent that is soaked up into a network depends on the

chemical potential of swelling agent in solution and gel (As mentioned in chapter one,

section 1.3.3). When the chemical potential inside and outside of the gel becomes equal,

the swelling process stops and the gel reaches equilibrium.

Degree of swelling in networks depends on several parameters and variables.

One of these variables is swelling agent molecular size or the radius of gyration (Rg)

when swelling agent is an oligomer or polymer. There are several theories to explain

effects of swelling agent size on diffusion rate such as the Obstruction theory and the

free volume theory. Entanglement in high molecular weight swelling agent can be

another factor which hinders and slows down swelling and diffusion rate. If the size

difference is very high, the chemical potential can be different in larger and smaller

swelling agent molecules. This factor can control molecular weight distribution of

swelling agent inside and outside of a gel. This swelling agent molecular weight

distribution difference between inside and out side of gel can increase when mesh size in

gel is small enough to hinder larger swelling agent molecules. This is very important in

200

this project, because, as will be shown later, the amphiphilic silicone copolymer which

is being researched for potential therapeutic effects on scars has a very broad molecular

weight distribution.

5.2 Swelling Study in PEG Based Networks

The reason PEG based gel has been synthesized in this project is the hypothesis

that the amphiphilic silicone copolymer with PEO side-arms will readily diffuse into

PEG networks. A PDMS network has been tested in this study as a potential carrier, but

the amphiphilic silicone copolymer did not diffuse into the network and swelling

percentage was negligible. This is due to the effect of the PEO side chains on the

solubility product of the oligomer compared to the PDMS network. In contrast these

groups act as a compatibilizer with the PEG-based network. Further in this chapter

DMTA results will show the compatibility and miscibility of the oligomeric siloxane in

the network. An obvious attractive feature is that PEG is biocompatible and a cost-

effective polymer.

In this research both water and amphiphilic silicone copolymer have been used

as the agents in swelling measurement and study. Water was used as a swelling agent,

because cold water is a relatively good solvent for PEG. As a result, all PEG hydrogels

can be swollen in water with relatively high swelling percentage. Also the enthalpy of

mixing between water and PEG causes the replacement of crystalline with amorphous

material which can eliminate almost all crystalline structure effects on hydrogel (noting

that crystalline regions act as physical crosslinks). It is very important to study purely

crosslink effects on network structures. This is because when there is any crystalline

region in network, mesh size will be limited between crosslinking junctions and

crystalline regions. When the gel sorbs water the latent heat of fusion (ΔHf) for

crystalline region can be satisfied by the heat of mixing (ΔHmix) between water and PEG

chain, which is mainly due to hydrogen bonding. Consequently, when crystalline

regions are transferred to amorphous region by water the hydrogel properties in water

such as mesh size are directly controlled by the crosslinking junctions.

When the swelling agent is an amphiphilic silicone copolymer, the swelling rate

and controlling parameters are totally different compared to the condition when water is

201

a swelling agent. This is because the amphiphilic silicone copolymer backbone is a

silicone chain which cannot diffuse into the PEG gels due to hydrophobic properties of

the silicone segment. The only factor that helps amphiphilic silicone copolymer

penetration into PEG networks is the short PEO side chains (as described in chapter one,

section 1.2.2) which cause compatibility between hydrophobic silicone chain and

hydrophilic PEG networks.

5.2.1 Swelling Study in PEG Hydrogels with Water as Swelling Agent

PEG hydrogel swelling properties can be tested using water and the percentage

of absorbed water is proportional to the mesh size in the hydrogel. For measuring water

absorption, a gravimetric analysis method was used. In Figure 5. 1 the percentage of

swelling versus time is shown. The swelling percentages were calculated based on

polymer fraction and in this calculation the silica fraction was excluded. The results

show the highest swelling amount is for hydrogel PEG2000AS0, because ultimate

swelling (swelling at equilibrium) is controlled by hydrogel modulus. In hydrogels

PEG2000AS20, PEG2000AV-S20 swelling percentages at equilibrium are the lowest.

For all hydrogels PEG2000AS0, PEG2000AS20, PEG2000AV-S20, PEG2000AP-S20,

PEG2000APEO-S20 and PEG2000APEO20-S20 swelling percentages level off almost

in the same time (below 500 min.). The highest slope is for hydrogel PEG2000AS0. The

results of swelling show percentages and rate of swelling can decrease when hydrogels

were reinforced by silica compared to PEG2000AS0 (un-reinforced). All these results in

Figure 5. 1 also show that the effective mesh size can change and get smaller in

reinforced hydrogels, although crosslink densities are exactly the same for all hydrogels

since all were synthesized using PEG 2000.

202

0

50

100

150

200

250

300

350

0 100 200 300 400 500 600 700

Time (min.)

% o

f Sw

ellin

g

PEG2000AS0 PEG2000AS20PEG2000AV-S20 PEG2000AP-S20PEG2000APEO-S20 PEG2000APEO20-S20

Figure 5. 1. Percentage of swelling of hydrogels PEG2000AS0, PEG2000AS20,

PEG2000AV-S20, PEG2000AP-S20, PEG2000APEO-S20 and PEG2000APEO20-

S20 in water. All calculations were done based on mass of polymer (PEG).

5.2.2 Swelling Study in PEG Networks with Amphiphilic Silicone Copolymer as

Swelling agent

5.2.2.1 Amphiphilic Silicone Copolymer

As mentioned in chapter 1, an amphiphilic silicone rake copolymer which

contains silicone backbone and PEO side chains is being researched as a potential

therapeutic agent for scar remediation (chapter 1 section 1.2.2).

A key feature of this rake silicone copolymer is its amphiphilic property. This is

because of hydrophobic backbone with hydrophilic side chains where the side chains act

203

as a compatibilizer. This property leads to penetration of the amphiphilic silicone

copolymer into PEG-based gels which is a less costly option for a therapeutic delivery

system rather than diffusion into a crosslinked PDMS gel.

Broad molecular weight distribution is a further, relevant property of this

copolymer when studying the sorption of it into a PEG-based network. This is because

according to Kwak [1], ultimate swelling percentage and diffusion coefficient are higher

when swelling agent molecular weight is lower where all other conditions are held the

same. This means the swelling agent with lower molecular weight diffuses faster and to

a higher level of swelling percentage compared to the same polymer with higher

molecular weight.

In Figure 5. 2 the amphiphilic silicone copolymer’s molecular weight

distribution is shown which was determined by GPC (chapter 2, section 2.7.4). The

breadth of the molecular weight distribution appears to arise from several overlapping

peaks. Since the molecular weight distribution of the amphiphilic silicone copolymer is

very broad, it should demonstrate the effect of molecular weight competition when a

network is immersed into it. It was expected that there would be some selectivity based

on size ie. lower molecular weight silicone copolymer diffuses in faster and in a higher

ratio compared to higher molecular weight silicone copolymer.

The other experiment which was done to investigate differences between

different chain lengths in amphiphilic silicone rake copolymer was 1H NMR on fractions

of the silicone copolymer. For separation of these fractions, Preparative GPC (chapter

two, section 2.7.4) was employed to separate amphiphilic silicone rake copolymer into

four fractions. It should be noted that the RI detector on the GPC can only detect

silicone copolymer because of the PEO side chains since pure silicone has a very close

refractive index to the THF mobile phase. As shown in the GPC results in Figure 5. 2

four fractions are identified and compared to GP226. Note that these fractions have been

analyzed separately on an analytical GPC to give the curves shown so they have not

been normalized to the amount of each fraction actually found in the GP226, which is

given in Table 5.1. (The percentage in this table was measured by a gravimetric

method).

204

Figure 5. 2. Amphiphilic silicone rake copolymer GP226 molecular weight

distribution (GPC). Four fractions of amphiphilic rake silicone copolymer were

separated and analyzed to give the individual curves.

Figure 5. 3 shows amphiphilic silicone rake copolymer and 1H NMR

assignments.

As shown in Table 5. 1, ratios between silicone backbone and PEO side chain (r)

in all fractions were calculated. These ratios in fraction 1, 2 and 3 are almost similar,

and the slight difference is due to backbone chain end groups. The end groups have

three CH3 instead of two for each silicon atom in the backbone. These results exhibit the

major difference between these three fractions is only size and they have very close ratio

of the silicone backbone to PEO side chains. However in fraction number 4 chemical

structures are totally different where species in this fraction are probably starting

material and are mainly unreacted allyl-terminated PEO or very small number of short

chains of PDMS-PEO copolymer. This result is confirmed by 1H-NMR in which linkage

groups between PEO side chain and PEMS backbone (d, f and h in Figure 5. 3) is lower

205

than other fractions. The ratio in neat silicone copolymer is lower than all fractions 1, 2

and 3, because ratio between PDMS and PEO in fraction 4 is very low.

Figure 5. 3. 1H NMR of amphiphilic rake silicone copolymer (Fraction 1) in CDCl3. In Table 5. 1, the percentage of each fraction in amphiphilic rake silicone

copolymer (GP226) is shown.

Table 5. 1. Ratio of proton in CH3 in PDMS to proton in CH3 in PEO

Frac. 1 Frac. 2 Frac. 3 Frac. 4

(a) PDMS 8.8 8.9 9.3 1.9 7

(b) PEO 1 1 1 1 1

r=PDMS/PEO 8.8 8.9 9.3 1.9 7

% in GP226 40% 36% 14% 10%

206

5.2.2.2 Crosslinked PEG as Gels for Amphiphilic Rake Silicone Copolymer

As a first step, the compatibility between amphiphilic rake silicone copolymer

and PEG networks needs to be studied. For compatibility investigation a DMTA method

was employed. DMTA is a very powerful technique to study miscibility and phase

behaviour of polymer blends and alloys.

If two polymers are fully miscible or compatible at the temperature of

measurement then both polymers stay together without any phase separation, and only

one α-transition temperature appears [2-4]. In this project a phase chemistry study has

been performed by DMTA for testing compatibility between PEG2000 gel swollen with

an amphiphilic rake silicone copolymer to different swelling percentages.

The glass transition temperature of the amphiphilic rake silicone copolymer was

measured by DSC and is around -83 °C (Figure 5. 4). The glass transition temperature of

PDMS is around -125 °C, but there is no glass transition temperature apparent in this

range for the amphiphilic rake silicone copolymer. This may be an effect of PEO side

chains on PDMS backbone which shifts the glass transition temperature to higher

temperature.

207

Figure 5. 4. DSC of amphiphilic rake silicone copolymer GP226.

Figure 5. 5. DMTA of swollen PEG2000AS0 containing amphiphilic rake silicone

copolymer GP226.

208

In Figure 5. 5, E’ and tan δ versus temperature of PEG2000AS0 swollen in the

amphiphilic silicone copolymer were measured. The different dry PEG network samples

were immersed in the amphiphilic silicone copolymer at 45 °C under an argon

atmosphere. At various times a DMTA test was performed on the swollen sample. Each

sample was used only for one run. In Figure 5. 5, there are no peaks observed around

-83 °C ( which is Tg as noted above) for any ratio of amphiphilic silicone copolymer and

the α-transition peaks in PEG2000AS0 swollen in the amphiphilic silicone copolymer

get broader with increasing amount of amphiphilic silicone copolymer sorbed. This

shows that PEG2000AS0 network and amphiphilic silicone copolymer are compatible.

During cooling process (down to around -90 °C) in DMTA, some amorphous regions

underwent recrystallization in the presence of amphiphilic silicone copolymer. The

cooling process takes place very fast in this technique, as a result, phase separation may

be slowed down or suppressed. This is because the kinetics of phase separation is

controlled by temperature, a rapid cooling (quenching) can lead to a stable single phase

which thermodynamically is considered as an unstable system. However, phase

separation cannot occur, unless all kinetic conditions (ie. temperature) reach the

minimum favorable for phase separation. Wang and colleagues reported [5],

morphology and kinetics in simultaneously crystallization and phase separation in

polymer blends depend on the rate of cooling process. The size and the shape of crystals

are seen different through the several rate of cooling, in addition, phase separation

depends on the crystallization rate and also the temperature. These two processes are

limited between two extremes, crystallization dominated and phase separation

dominated.

E’ values drop as the amount of amphiphilic silicone copolymer in the gel

increases. This means the amphiphilic silicone copolymer acts as a plasticizer in PEG

gels. The α’-transition shifts to lower temperature and become broader by increasing the

amount of the amphiphilic silicone copolymer. These changes show the crystalline

region structures can change by increasing percentage of the amphiphilic silicone

copolymer.

The results in DMTA were checked by DSC (step crystallization method) in

Figure 5. 6. The crystal transition temperatures shifted to lower temperatures when

209

swelling percentage of silicone copolymer increased. These shifts in temperature are

similar to the shifts in E’ in DMTA in Figure 5. 5. The endothermic peaks (from around

-30 to 0 °C) in both PEG2000AS0 samples swollen in the amphiphilic silicone

copolymer (14 and 26%) are melting points in silicone copolymer which can be seen by

the DSC result in Figure 5. 4.

Figure 5. 6. DSC results in PEG2000AS0 before and after swelling with 14 and

26% of silicone copolymer.

To study the effect of molecular weight on diffusion process through gels, the

silicone copolymer can be applied to the gel and molecular weight distribution of

supernatant liquid can be monitored and examined by GPC. In this experiment the gel

was immersed in amphiphilic rake silicone copolymer (GP226) for 3 weeks to reach

equilibrium. Molecular weight distribution differences in supernatant liquid and

amphiphilic rake silicone copolymer (GP226) indicates the size of amphiphilic rake

silicone copolymer which preferentially diffused into the gel. It is obvious that this test

is qualitative and depends on the starting amount of amphiphilic rake silicone copolymer

210

(GP226). As an example in Figure 5. 7, comparison between chromatograms of silicone

copolymer and supernatant liquid of silicone copolymer after contact with the gel are

given. This shows shorter species diffused into the gel preferentially compared to longer

chains, in spite of the concentration of shorter chains being very much lower than

concentration of longer chains in the neat silicone copolymer (Table 5. 1).

Figure 5. 7. GPC chromatograms of pure silicone copolymer and supernatant

liquid of silicone copolymer on top of the gel.

For checking the accuracy of this experiment the silicone-loaded gel (swollen

gel) was kept in THF for several days to extract all silicone copolymer which had

diffused into the gel. The extracted silicone was injected into the analytical GPC to

check molecular weight distribution after diffusion inside the gel (Figure 5. 8). This

result confirmed the outcome of testing supernatant liquid in Figure 5. 7.

211

This result is particularly significant since recent studies [6] show that the most

biologically active fractions of the amphiphilic copolymer are those corresponding to a

retention time from 25 to 27 min. or Fraction IIIb as shown in Figure 5. 2. The network

is thus able to fractionate the copolymer and preferentially absorb the lower molar mass

fractions which are believed to be the most effective in down-regulating collagen

production and thus most effective in scar remediation.

Figure 5. 8. GPC chromatograms of pure silicone copolymer and the extracted

silicone copolymer from the gel.

In Figure 5. 9, equilibrium sorption data for the amphiphilic silicone copolymer

in UV-cured PEG2000 gels with different functionalized silica and without silica are

shown. These tests were done at room temperature. The results show very low variation

in swelling percentages between different reinforced and non-reinforced gels. This is

probably because the percentages of swelling in all gels at equilibrium are low.

The swelling percentages in bis acrylate PEG 2000 gels are lower compared to

PEG2000 gels which were made by sol-gel synthesis method (shown in Figure 5. 10).

This can be caused by higher crystal transition temperature in bis acrylate PEG 2000

gels compared to in situ silsesquioxane PEG2000 gels synthesized by the sol-gel

212

method. Unlike when water is the swelling medium, the crystalline regions of the UV-

cured PEG gel cannot be penetrated and disrupted by the silicone at room temperature.

Thus swelling can only occur into the amorphous region and the crystalline blocks

reduce the available volume for penetration as well as the mesh size.

0

5

10

15

20

25

30

PEG2000AS0

PEG2000AS20

PEG2000AV-S20

PEG2000AP-S20

PEG2000APEO-S20

PEG2000APEO20-S20

% o

f Sw

ellin

g in

GP2

26

Figure 5. 9. Ultimate percentages of swelling of PEG2000 gels (UV cured) in

silicone copolymer with different silica and without silica.

The other swelling experiments were done on gels which were synthesized by

the sol-gel method. Gels which were synthesized by the sol-gel method have different

crosslink structures compared to the UV curing method of synthesis. The number of

functional groups in bis(triethoxy silyl propyl urethane)-PEG is 6 functional groups, but

each chain in bis acrylate PEG has only 2 acrylate groups as chain end. The other factor

is mechanism of reactions which are different between sol-gel reaction and UV curing

reaction.

All gels which were synthesized by sol-gel reaction method were examined at

room and 50 °C temperatures. As will be discussed in this section all gels did not show

213

any significant change in swelling percentages except PEG4600 gels. All gels

equilibrated in silicone copolymer at 50 °C were then kept at room temperature and the

equilibrium silicone content measured. The temperature decrease to around 23 °C (RT)

causes crystallization and chemical potential changes. As mentioned in this section,

simultaneous phase separation and crystallization process affect the final polymer blends

morphology and composition. The result shows the crystallization process may be a

dominant process. This observation needs more experiments in the gels with several

different molecular weights.

0

5

10

15

20

25

30

35

40

45


% o

f Sw

ellin

g in

GP2

26

Figure 5. 10. Ultimate percentages of swelling of gels PEG2000SW1,

PEG2000SW2, PEG2000SW3 and PEG2000SW4 when immersed in amphiphilic

silicone copolymer.

In Figure 5. 10 swelling percentages of gels PEG2000SW1, PEG2000SW2,

PEG2000SW3 and PEG2000SW4 (as was discussed in chapter 3, section 3.2.3.1.2) in

amphiphilic silicone copolymer are shown. The percentages of swelling of gels in

amphiphilic rake silicone copolymer increase from gel PEG2000SW1 to PEG2000SW4

(with the swelling percentage in gels PEG2000SW3 and PEG2000SW4 being very

close). This trend of increase in amphiphilic silicone copolymer is very similar to the

214

trend of swelling increase in water with the same samples which was discussed in

chapter 3, section 3.2.3.1.2 and Figure 3. 25. This trend of swelling increase of gels in

amphiphilic silicone copolymer verifies the crosslink structures changes during

increasing amount of 0.1M HCl from high to low density crosslink structures.

The effects of HCl concentration used during synthesis (PEG2000SH1,

PEG2000SH2, PEG2000SH3 and PEG2000SH4) on percentage of swelling of the gels

when immersed in amphiphilic silicone copolymer are shown in Figure 5. 11. The trends

of swelling percentage increase of the same hydrogels in both water (chapter three,

section 3.2.3.1.3 and Figure 3. 30) and amphiphilic rake silicone copolymer as swelling

agents are very similar within error.

0

5

10

15

20

25

30

35

40

45


% o

f Sw

ellin

g in

GP2

26

Figure 5. 11. Ultimate percentages of swelling of PEG2000 gels which were

synthesized (sol-gel method) with different concentration of acidic water and

immersed in amphiphilic silicone copolymer.

Figure 5. 12 shows that dangling chains in gels have an effect on swelling

percentages in amphiphilic rake silicone copolymer. The trends of swelling in both

water (Figure 3. 17) and amphiphilic rake silicone copolymer are similar although the

total % change is much smaller in the silicone. Both of these results in two different

215

swelling agents prove dangling chain and density of crosslink structures have an effect

on swelling and gel behaviour. As mentioned in chapter three, section 3.2.3.1.1, the

crystal transition shifts to higher temperatures with the increased number of dangling

chains. The structure of swelling agents (ie. water and silicone copolymer) and the

interaction between them and the network can control the percentage of swelling. The

interaction between water and the network in a PEG hydrogel is greater than this

interaction between silicone copolymer and a PEG gel. As a result, crystalline regions in

the gel act as a virtual crosslink when the swelling agent is silicone copolymer and as in

Figure 5. 6 it is seen that silicone copolymer cannot dissolve all the crystalline regions.

0

5

10

15

20

25

30

35

40

45

50

PEG2000SWD0

PEG2000SWD1

PEG2000SWD5

PEG2000SWD10

PEG2000SWD15

PEG2000SWD20

% o

f Sw

ellin

g in

GP2

26


synthesized (by a sol-gel method) with different percentage of dangling chains in

amphiphilic silicone copolymer.

In Figure 5. 13, the effects of silica on percentage of swelling of reinforced gels

in amphiphilic rake silicone copolymer are shown. (All swelling percentages were

calculated based on PEG portion only of the reinforced gels). The percentage of

swelling increases when the fraction of silica increases in the reinforced gels. This can

be caused by either an effect of silica on crosslink structures or interactions between

silica and amphiphilic rake silicone copolymer.

216

The trend in Figure 5. 13 does not follow the same trend in the same reinforced

hydrogels when they were swollen in water (this was discussed in chapter three, section

3.2.3.1.8.1, Figure 3. 49). The percentages of swelling in the reinforced hydrogels in

water decrease on increase in the percentage of silica. To understand this different

swelling trend in water and silicone copolymer further experiment with different

techniques is required such isothermal DMA (dynamic mechanical analysis) with

frequency sweep. These different trends between water and amphiphilic rake silicone

copolymer show swelling percentages in these two swelling agents depend on

interactions between silica, PEG and swelling agents. This is because if the presence of

silica changed only the crosslink structures, the swelling percentages in both water and

silicone copolymer should follow the same swelling pattern (with different value in

water compared to silicone copolymer). However, they show an increased trend in

silicone copolymer and a decreased trend in water. As shown in section 1.2.2, equation

1.1, amphiphilic rake silicone copolymer has PDMS backbone and methyl ether

terminated PEO as side chains. It is possible the backbone shows some interactions with

surface of silica, whereas water cannot have the same interactions with the amphiphilic

copolymer.

0

10

20

30

40

50

60

PEG2000SWS1 PEG2000SWS5 PEG2000SWS10 PEG2000SWS20

% o

f Sw

ellin

g in

GP2

26

217


synthesized (sol-gel method) with different percentage of silica when immersed in

amphiphilic silicone copolymer.

The results in Figure 5. 14 show the effects of gel structure of PEG4600SH1,

PEG4600SH2, PEG4600SH3 and PEG4600SH4 (chapter two, section 2.4.2.1) for which

swelling measurements were done at 50°C and room temperature. As the results show,

at 50 °C these gels exhibit relatively higher swelling percentages compared to other gels

(all un-reinforced PEG2000 gels) and all PEG4600 gels at room temperature. This is

possibly because crosslink structures in PEG4600 gels can alter the network structures

in both mesh size and crystalline structures. At higher temperature PEG4600 gels have a

higher amorphous fraction compared to the same gels at a lower temperature (room

temperature). When the temperature of a previously swollen gel was decreased to room

temperature, packing took place and amphiphilic rake silicone copolymer was forced to

release from the gel. These changes on the temperature decrease from 50oC to room

temperature are shown in Figure 5. 14.

0

10

20

30

40

50

60


% o

f Sw

ellin

g in

GP2

26

50 °C RT

Figure 5. 14. Ultimate percentages of swelling of PEG4600 gels (PEG4600SH1,

PEG4600SH2, PEG4600SH3 and PEG4600SH4) when immersed in silicone

copolymer at 50oC and at Room temperature (RT).

218

In Figure 5. 15, percentages of swelling of PEG400SW1, PEG400SW2,

PEG400SW3 and PEG400SW4 gels (chapter two, section 2.4.2.1) in amphiphilic

silicone copolymer are shown. The results exhibit no trend or order when the amount of

0.1M HCl used in synthesis increases. These results confirm that when the polymer

average molecular weight in gels drop below the certain level, crosslink structures

cannot be altered by amount of 0.1M HCl solution added during synthesis.

0

5

10

15

20

25


% o

f Sew

lling

in G

P226


synthesized (sol-gel) with different amount of 0.1M HCl (PEG400SW1,

PEG400SW2, PEG400SW3 and PEG400SW4) in silicone copolymer.

5.2.2.3 Effect of Amphiphilic Silicone Rake Copolymer Size on Swelling

Percentage and Profile in Gels

For further study of swelling agent size effects on percentage of swelling,

fraction three (Figure 5. 2) was separated through the Preparative GPC (as mentioned in

chapter two, section 2.7.4) as a smaller average molecular weight and narrower

molecular weight distribution compared to original amphiphilic rake silicone copolymer

(GP226).

219

This is the therapeutically active fraction which is to be delivered by the gel

system so the network properties must be optimized for uptake and delivery of this

fraction. Comparison between swelling at equilibrium in fraction three and GP226

shows effect of molecular size on swelling (Figure 5. 16). The results show swelling

percentages increase when amphiphilic silicone copolymer size becomes smaller. The

effects of polymer size (both size and entanglement number) have been discussed in

section 5.2.2.1 [1].

0

10

20

30

40

50

60

70

80

90

100


% o

f Sw

ellin

g in

Sili

cone

Cop

olym

er

GP226 Frac. 3

Figure 5. 16. Swelling percentage in fraction 3 and GP226 at gels (PEG2000SW1,

PEG2000SW2, PEG2000SW3 and PEG2000SW4).

The results in Figure 5. 16 show that when mesh size in the gels becomes larger

(chapter three, section 3.2.3.1.2 and Table 3. 1) the percentage of swelling in both

silicone copolymer (GP226) and fraction three silicone copolymer increases. The

possible explanation is the gel can act as a size exclusion network so that when the mesh

size gets larger more silicone copolymer with bigger molecular size can diffuse in. As

shown in Figure 5. 2, fraction three has a broad molecular weight distribution with two

peaks, although it is narrower compared to the molecular weight distribution in GP226.

220

5.3 Desorption of Amphiphilic Silicone Rake Copolymer from Swollen Gels

The main goal in this research is synthesis of gels to deliver a therapeutic

amphiphilic silicone rake copolymer. In this section a method for measuring and

analyzing the desorption rates from different gels into water (simulating the topical

application of the gel on human skin) will be discussed. The gels for release studies

were chosen to cover a range of mesh sizes and are those PEG2000 gels used for the

uptake studies in Section 5.2.

As mentioned in chapter one, section 1.2.2 and section 5.2, the amphiphilic

silicone rake copolymer contains PDMS as a backbone and PEO as side chains. Both

backbone and side chain cannot be detected by conventional methods such as UV

spectroscopy analysis. Also the silicone copolymer stays in the gel only as long as the

swollen gel is in a dry condition. As a consequence, gravimetric analysis method cannot

be employed to study desorption of the silicone copolymer since there will be a

simultaneous uptake of water by the gel to become a hydrogel. The other possible

methods are Raman and FTIR spectroscopy analysis which can unambiguously identify

and quantify the release of the silicone copolymer. Raman spectroscopy is insensitive to

water but has a very low sensitivity to silicone (in general due to low polarizability of

Si-O bonds). In contrast, the signal in FTIR spectroscopy is very strong in silicone but it

cannot be used in the presence of water.

The technique that has been used in this research is quantitative liquid 1H-NMR

in deuterium oxide (D2O) with pyridine as an internal standard. The internal standard

concentration during successive experiments needs to be constant (the concentration of

pyridine was checked by UV spectroscopy at several different times and it was

constant). Pyridine has been selected due to its lower interaction with PEG chains. Lone

pairs in pyridine and in PEG are donors, as a result, they are not able to hydrogen bond

to one another.

Gels (PEG2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4)

previously swollen in fraction three of the amphiphilic silicone copolymer GP226

(Figure 5. 16) were immersed in D2O with 0.3% pyridine. As shown in Figure 5. 1 a dry

network when immersed in water reaches equilibrium in around 300 minutes, so in this

221

case release takes place through a swollen hydrogel and silicone copolymer diffuses

through the meshes inside the hydrogels that are created or become larger with D2O. In

the early stage of desorption process, when D2O is diffusing into the gels, two opposing

diffusion processes can take place: One is D2O penetration into the network and the

second is release of silicone copolymer from the D2O swollen area in hydrogels. At

equilibrium (in D2O) only diffusion via the swollen meshes can occur.

1H-NMR with water suppression technique to eliminate the water peak has been

employed to measure silicone concentration increases with time in solution.

As shown in Figure 5. 17, pyridine has 3 peaks from 7.3 to 8.6 ppm and the

middle peak (p) is used as the standard peak for pyridine. In silicone copolymer, fraction

three, peaks a (CH3-Si), b (CH3-O-CH2-CH2 end of PEO) and c (-CH2-CH2-O-) are

shown in the structure in Figure 5. 3.

Figure 5. 17. 1H-NMR spectrum of fraction three of GP226 in D2O with 0.3%

pyridine for silicone concentration measurement during desorption.

In this study only peaks a and c were considered for measurements since peak b

has a very low molar concentration (being an end group of PEO side chains) and is

therefore insensitive. Standard calibration curves for fraction three and for PEG 2000 Da

are provided compared to the area under the curve of peak p as unity (Figure 5. 18 and

222

Figure 5. 20). The reason a standard calibration curves needs to be used is silicone

copolymer does not have any unique hydrogen in its structure which can be compared

with pyridine peak (p). Therefore, calibration curves are provided for the same

conditions as the desorption experiment.

C = 1.2755xA- 0.1011R2 = 0.9933

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

0 0.5 1 1.5 2 2.5 3 3.5Area Under NMR Peak (A)

Con

cent

ratio

n (m

g/m

l)

Figure 5. 18. Standard calibration curve in the CH3-Si (peak a) compared to area

under curve of peak p (pyridine) as unity.

Release of silicone copolymer from gels based on CH3-Si (peak a) and PEO

(peak c) which are normalized to swollen gels (to make the results independent of the

weight of swollen gels) are shown in Figure 5. 19 and Figure 5. 21, respectively. In

Figure 5. 19, in the first stage of release a rapid non-linear silicone copolymer

concentration increase is observed, then, after around 200 hours a linear stage of release

occurs. (Note: release measurement was started after 16 hours after immersing the gels

in D2O due to low molar concentration of silicone copolymer in D2O that is hard to

detect in NMR).

The first stage of release in Figure 5. 19 may occur due to diffusion release

mechanism through the outer layer of the gels that are swollen in D2O. The intrinsic

scatter in the data results in several release concentration data points being negative at

223

short time, which is impossible. (The possible reason may be the analytical insensitivity

of 1H-NMR at low molar concentrations of silicone copolymer in D2O solution in these

data points.) In the second stage of release (above 200 hours), the release profiles are

linear indicating a time-independent release mechanism. Generally, time-independent

release profile is desired in drug delivery systems, because the rate of release over a

large period of time is constant and independent of drug concentration inside the gel.

The results also show the effect of different gel structures on the rate of release.

These four gels have different mesh size and crosslink structures, although all gels were

synthesized from the same average molecular weight PEG (2000 Da) (as discussed in

section 5.2.2.3). This observation shows that the novel method of synthesis which was

described in chapter three and in chapter one, section 1.5.2, can control the release rate

from gels.

-0.005

0

0.005

0.01

0.015

0.02

0.025

0.03

0.035

0 200 400 600 800

Time (hr)

Wei

ght o

f Fra

ctio

n 3

(mg)

per

Uni

t of

Swol

len

Gel

Wei

ght (

mg)


Figure 5. 19. Amount (normalized to starting weight of swollen gel in fraction

three) of released silicone copolymer based on CH3-Si (peak a in Figure 5. 17) from

gels G2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4 into D2O.

224

As mentioned in chapter one, section 1.3.2, in diffusion release mechanism, the

desorption concentration changes gradually with the specific rate which depends on the

regime of diffusion (Fickian and Anomalous transport) up to a certain level of

concentration (C∞), then the concentration levels off. However, as shown in Figure 5. 19

after around 200 hours the diffusion mechanism transforms to a linear release

mechanism. For better understanding of the release mechanism in these gels, PEO

concentration profiles were considered (Figure 5. 21). The concentration of PEO groups

in D2O increases linearly (zero-order or time independent release). (The first data points

are started at 16 hours). However, when compared in absolute terms, the values of

release in the same time in Figure 5. 21 (the calculated value based on PEO) is several

times higher than the calculated value based on the CH3-Si peak shown in Figure 5. 19.

The other difference between results in Figure 5. 21 and Figure 5. 19, are linear release

profile from the starting points of the release based on PEO concentration, but as

mentioned earlier, in the first stage of the desorption based on the CH3-Si peak,

diffusion release takes place.

C = 1.1627xAR2 = 0.9995

0

5

10

15

20

25

0 5 10 15 20

Area Under NMR Peak (A)

Con

cent

ratio

n (m

g/m

l)

Figure 5. 20. Standard calibration curve in PEG 2000 Da (peak c) compared to

area under curve of peak p (pyridine) as unity.

225

0.02

0.04

0.06

0.08

0.1

0.12

0.14

0 200 400 600 800

Time (hr)

Wei

ght (

mg)

per

Uni

t of S

wol

len

Gel

Wei

ght (

mg)


Figure 5. 21. Amount (normalized to starting weight of swollen gel in fraction

three) of released silicone copolymer based on PEO and PEG signals in the 1H

NMR from PEG2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4 gels

into D2O.

One of the possible explanations for the high concentration of PEG released at

short times is that the hydrogel is hydrolyzed from the in situ silsesquioxane crosslinker.

This produces a degradation mechanism for release of the silicone (ie linear with time)

in the late stage of desorption, and there is decomposition of the hydrogel producing a

PEG impurity in D2O for NMR analysis. The degradation-controlled release from

hydrogels was discussed in chapter one, section 1.3.2 part 3.

The in situ silsesquioxane crosslinker links to PEG chains through the urethane

linkage. Degradation may occur through hydrolysis of the urethane linkage or at the

crosslinking site (in situ silsesquioxane) in the presence of pyridine as a base. This

226

hydrolysis and degradation can progress at a rate that is controlled by the in situ

silsesquioxane structures (as shown in Figure 5. 21 with different rate of release of PEG

and PEO). This can be the reason for the different rate of PEO release in between gels

PEG2000SW1, PEG2000SW2, PEG2000SW3 and PEG2000SW4. This is able to

explain the difference between the two results for release kinetics based on NMR

analysis of the concentration of PEO and CH3-Si groups. As a result, the released PEO

comes from two surces: 1. PEO side chain in silicone rake copolymer and 2. PEG based

hydrogel chains.

0

0.005

0.01

0.015

0.02

0.025

0.03

0.035

0.04

0.045

0 20 40 60 80 100 120 140 160

Time (hr)

Wei

ght (

mg)

per

Uni

t of D

ry N

etw

ork

(mg)

PEG2000SW4

Figure 5. 22. Amount (normalized to starting weight of dry network) of PEG

signals in the 1H NMR from a blank PEG2000SW4 hydrogel (without fraction

three of silicone) into D2O.

To understand degradation of a blank hydrogel in the same conditions, dry

PEG2000SW4 network (without fraction three silicone copolymer) was immersed in

D2O, with the same amount of pyridine as internal standard, and the concentration

increase in PEG was monitored by 1H-NMR. The result in Figure 5. 22 shows in the

early stage of experiment (up to 7 hours) PEG is released from the hydrogel very fast,

and in the next stage the PEG concentration in solution increase in a zero-order release

227

mechanism (linear and time independent). The hydrogel has been washed before this

experiment so the only source of PEG must be degradation of the hydrogel. For a better

understanding of hydrogel degradation, the released PEG solution from blank

PEG2000SW4 hydrogel was evaporated on the ATR crystal. The FT-IR result shows in

Figure 5. 23 and is compared with bis(triethoxy silyl propyl urethane) PEG 2000. The

carbonyl in urethane linkage is seen in the released PEG which tells the hydrolysis took

place from in situ silsesquioxane crosslinker. This result illustrates the release

mechanism of the silicaone rake copolymer from the hydrogels may be both diffusion

and a degradation-controlled release mechanism.

Wavenumbers (cm--1)

15002000250030003500

.00

.02

.04

.06

.08

.10

Silane PEG Extracted Silane PEG

Figure 5. 23. FT-IR spectra of silane PEG and silane PEG extracted from blank

PEG2000SW4 hydrogel into D2O.

In order to determine if this hydrolysis can occur under conditions encountered

when used on the skin it is necessary to consider the hydrolytic stability by methods

other than NMR.

228

5.4 Summary

In this chapter the swelling and deswelling of PEG networks (synthesized as described

earlier) in an amphiphilic silicone-PEG rake copolymer has been studied. The silicone

copolymer (which has been shown by others to down-regulate collagen production) has

been characterized here by NMR and GPC to determine the structure and molecular

weight distribution.

To study the compatibility between this silicone copolymer (the swelling agent) and

PEG network, DMTA was employed at different swelling percentages. The chemical

potential (and thus diffusion) is related to the amphiphilic silicone rake copolymer

molecular size and broad molecular weight distribution (MWD). The broad MWD

suggests the copolymer has several different components and to study molecular weight

distribution of amphiphilic silicone rake copolymer when diffused into the PEG gel,

both supernatant and extracted amphiphilic silicone rake copolymer from gel were

analyzed with GPC. The result showed the smaller molecule diffuse relatively faster

than the larger molecules. For further investigation, swelling measurements have been

examined in different fractions of the silicone and the higher swelling has been seen in

lower molecular weight fraction.

The effects of crosslink structure, filler and length of polymer chain on swelling of the

network by the amphiphilic silicone copolymer have been studied. The trend of swelling

is seen from silsesquioxane-crosslinked PEG2000 networks synthesized with different

concentrations of HCl solution which followed the same trend as seen earlier in the

water swelling test. The effect of dangling chains on silsesquioxane-crosslinked

PEG2000 networks is to also increase the uptake of silicone.

Interestingly, the effect of an increase in the amount of silica added to silsesquioxane-

crosslinked networks is to increase the uptake of silicone copolymer. It is possible that

the backbone of silicone copolymer has some interaction with the surface of silica which

results in the higher swelling percentage.

229

The effect of polymer chain length between two crosslinking sites on swelling in

silicone copolymer has been tested. The swelling percentage in the same gel with longer

chain length (4600 Da) is different at room temperature and 50 °C. When temperature

drops, polymer chains may commence crystallization. This causes exclusion of the

amphiphilic silicone rake copolymer by the polymer chains packed in a crystalline

region, and silicone copolymer is pushed from the gel mesh.

Desorption tests were done in water from gels which were previously swollen to

equilibrium in the fraction of the amphiphilic silicone rake copolymer which is

biologically active (fraction 3). Quantitative 1H-NMR technique was used to detect the

increase in silicone copolymer concentration when the gel was immersed in deuterium

oxide (D2O). The results show that in early stage of release, Fickian diffusion occurs

and in the next stage, the possible mechanism of release is zero-order ie. a time-

independent mechanism. The differences between results in PEO and silicone backbone

measurements show it is most likely that the release rate is controlled by both diffusion

and hydrogel hydrolysis (a type of network degradation release). A better understanding

of release mechanisms needs further experiments.

The desorption results in four different networks which were swollen in fraction 3 of the

silicone copolymer up to equilibrium show the effect of mesh size differences on the

desorption profile, although all networks were synthesized with the same precursor

(bis(triethoxy silyl propyl urethane)-PEG2000) through the sol-gel reaction. These

results indicate that both the amount and rate of release can be altered with sol-gel

reaction conditions."

230

References

1. Kwak, S., Lafleur, M., Raman Spectroscopy as a Tool for Measuring Mutual-Diffusion Coefficients in Hydrogels. Appl. Spectosc., 2003. 57(7): p. 768-773.

2. Mendes, L., Tavares, M. and Mano, E., Compatibility of iPP/HOCP Binary Blends by OM, DSC, DMTA and 13C Nuclear Magnetic Resonance. Polym. Test., 1996. 15(1): p. 53-68.

3. Mihaylova, M., Kresteva, M., Perena, J. and Phillips, P., Dynamic Mechanical Properties of Polymer Blends of Polypropylene and PoIy(Ethylene-co-Vinyl Acetate) Irradiated with Fast Electrons. Bulg. J. Phys., 2001. 28: p. 85-94.

4. Haponiuk, J., Tercjak, A., Dynamic Mechanical Thermal Analysis of Polyamide 6/Biopol Blends. J. Therm. Anal. Cal., 2000. 60: p. 313-317.

5. Wang, H., Shimizu, K., Kim, H., Hobbie, E., Wang, Z. and Han, C., Competing Growth Kinetics in Simultaneously Crystallizing and Phase-Separating Polymer Blends. J. Chem. Phys., 2002. 116(16): p. 7311-7315.

6. Lynam, E., Xie, Y., Loli, B., Dargaville, T., Leavesley, D., George, G. and Upton, Z., The effect of amphiphilic siloxane oligomers on fibroblast and keratinocyte proliferation and apoptosis. J. Biomed. Mater. Res. Part A, 2010. 95A (2): p. 620-631.

231

Chapter 6: Future work

The method of synthesis of PEG-based hydrogels in this research is novel and

several different aspects of this method of network formation have not been investigated

in the time available.

The sol-gel method of network formation needs more fundamental studies. For

example there needs to be exploration of other variables in the synthesis of in situ

silsesquioxane-reinforced networks such as different catalysts. For tailoring the gels for

optimum release and swelling, a study of the kinetics of sol-gel reaction is essential.

Kinetics of hydrolysis and condensation reactions change the final in situ silsesquioxane

structures and nano-particle size which ultimately alter mesh size and crystallinity in dry

networks. For this investigation 29Si (both liquid and solid) NMR are needed and for

enhancement of NMR sensitivity, 29Si isotope-enriched silane is needed.

Investigation of crystalline and crosslink structures in networks which are

formed by sol-gel method of synthesis with different pH, amount of water and

temperature also needs to be done. A deeper study of the crosslink structures can be

done by silicon NMR in which all shifts of T1, T2 and T3 structures in NMR are required

to be assigned. Crystalline structures can be further studied with DSC and DMTA to

enable both the α-transition and the α’-transition to be investigated. This can enable

further study of the effects of crosslink structures on the glass transition temperature.

Fundamental study on in situ silsesquioxane network degradation in water with

different pH is needed to understand differences in the rate of desorption of the

amphiphilic silicone copolymer based on the degradation mechanism for release in the

hydrogels. The mechanisms of swelling and desorption in silica reinforced gel need to

be studied to better understanding differences between water and amphiphilic silicone

copolymer interactions with hydrogels.

The commercial amphiphilic silicone rake copolymer used here (GP226) has a

very broad molecular weight distribution and batch-to-batch variability. This type of

molecular weight distribution prevents its use as a model compound for swelling and

232

release study. Fractionation and separation of amphiphilic silicone rake copolymer

(GP226) with preparative GPC for large scale separation is very costly and takes a very

long time. Further study using the narrower fraction IIIb of amphiphilic silicone rake

copolymer to study mechanisms of migration into and release from PEG hydrogels is

essential, because biological studies which have been done at Queensland University of

Technology (QUT) show the down-regulation of collagen production by fibroblasts

depends on the molecular size of amphiphilic silicone rake copolymer[1].

In separate research at QUT, a range of amphiphilic silicone rake copolymers

which have different PEO chain length and different ratio between backbone (PDMS)

and PEO (different number of side chains) have been synthesized [1, 2]. These changes

in amphiphilic silicone rake copolymer can change chemical potential which is driving

force for swelling and release and this provides an opportunity to study swelling and

release measurement and mechanism with narrow molecular weight oligomers of

precisely known structure.

There also needs to be further study of the release of the siloxane oligomers from

the hydrogel directly on to human skin. This can be initially performed by in vitro

measurements of migration into excised whole human skin using a Franz Cell [2] or an

ATR-FTIR method [3]. This will enable a partitioning efficiency between the hydrogel

and the skin at body temperature to be determined.

Investigation of biological efficiency of silicone copolymer delivery via gels on

the cells (hypertrophic fibroblasts) responsible for over-production of collagen and thus

scar formation compared to conventional method should be undertaken. This can help to

better understand and tailor the network with optimum properties for scar remediation.

In vitro tests with swollen gel can show cell response to the hydrogel. Separate

cytotoxicity tests would need to be undertaken on the in situ silsesquioxane crosslinked

hydrogels, even though PEG is a biocompatible polymer.

For a practical gel, mechanical integrity under the conditions of use is essential.

A much deeper study of the mechanical properties of hydrogels (tensile and compressive

tests) formed by novel synthesis (sol-gel reaction) is required. Effects of silica with

different surface modifications on the mechanical properties of in situ silsesquioxane

233

PEG hydrogels need more investigation. Comparison of reinforcement effects of

different silica on networks which are formed with different crosslinking reactions can

show simultaneous effect of different reinforcement agents and different crosslink

structures on the final products mechanical properties. This should lead to hydrogel with

properties optimized for a viable therapeutic delivery system: uptake; release and

mechanical strength.

References:

1. Dickfos, M., "Spectroscopic studies of the transdermal delivery of active silicone for scar remediation." Honours Thesis, QUT School of Physical and Chemical Sciences, November, 2008.

2. Dargaville, T., Keddie, D., Lynam, E., Upton, Z. and George, G., Interactions of Silicones and Biological Systems. Abstracts of 11th Pacific Polymer Conference, Cairns, 2009.

3. Sanchez, W., Evans, J. and George, G., Silicone Polymers in Scar Remediation: The Role of Migration of Oligomers Through Stratum Corneum. Aust. J. Chem., 2005. 58: p. 447-450.

Documents

REINFORCED HYDROGELS FOR SCAR REMEDIATION · 2011-03-28 · Polymer Nanostructured-materials, RMIT , Melbourne, June 2009. B. Radi, M. Wellard and G. George, “Sol-gel Reactions