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Centro de Graduados e Investigación en Química, Instituto Tecnológico
de Tijuana.
A. P. 1166. Tijuana, B. C. 22000, México. E-mail: [email protected]
Norma Aidé Cortez-Lemus, 2019
Star-shaped poly(N-vinylcaprolactam) and copolymers
❖High density of internal and peripheral functional groups
compared to linear polymers of similar molecular weight
❖Synthesis of star polymers with a precise number of arms
❖The star polymers exhibit lower solution viscosity in dilute
solutions
❖Smaller hydrodynamic volume
❖Amphiphilic star block copolymers can encapsulate
efficiently drugs
Importance of the study of star-shaped
polymers
Kowollik, B. C.; Davis, P. T.; Stenzel, H. M. Aust. J. Chem. 2006,
59, 719-727.
Comparison of star synthesis using the core-first
technique using the Z-group (left) and R-group (right)
approaches.
G. D. García-Olaiz, K. A. Montoya-Villegas, A. Licea-Claverie, N. A. Cortez-Lemus. Synthesis andcharacterization of four- and six-arm star-shaped poly(ε-caprolactone)-b-poly(N-vinylcaprolactam): Micellar and core degradation studies. Reactive & Functional Polymers2015, 88, 16-23.
PNVCLPEGPEHA
(PVAc-b-(PNVCL-co-PNVP))6
(PNVCL-co-PNVP)6
(PNVCL)6
((PNVCL-co-PNVP)-b-PVAc)6
(PNVCL-b-PVAc)6
Poly(N-vinylcaprolactam) (PNVCL)
Poly(N-isopropylacrylamide) (PNIPAM)
Thermally responsivepolymers
LCST ~32 °CLCST ~30-50 °C
C=O ---- H-N
Internal hydrogen-bond:
Flory–Huggins type I
Flory–Huggins type II
Biocompatible
Thermosensitive polymers
Influence of End Groups on aqueous
properties of thermosensitive polymers
The LCST decreased or increased in thermosensitive polymers having
hydrophobic or hydrophilic end groups.
Solubility
Strong influence of end-groups on activity and cytotoxicity in
antimicrobials polymers.
G. D. García-Olaiz, K. A. Montoya-Villegas, A. Licea-Claverie, N. A. Cortez-Lemus. Synthesis andcharacterization of four- and six-arm star-shaped poly(ε-caprolactone)-b-poly(N-vinylcaprolactam): Micellar and core degradation studies. Reactive & Functional Polymers2015, 88, 16-23.
G. D. García-Olaiz, K. A. Montoya-Villegas, A. Licea-Claverie, N. A. Cortez-Lemus. Synthesis andcharacterization of four- and six-arm star-shaped poly(ε-caprolactone)-b-poly(N-vinylcaprolactam): Micellar and core degradation studies. Reactive & Functional Polymers2015, 88, 16-23.
G. D. García-Olaiz, K. A. Montoya-Villegas, A. Licea-Claverie, N. A. Cortez-Lemus. Synthesis andcharacterization of four- and six-arm star-shaped poly(ε-caprolactone)-b-poly(N-vinylcaprolactam): Micellar and core degradation studies. Reactive & Functional Polymers2015, 88, 16-23.
Fig. 1. 1H NMR spectra (200 MHz) of six-arm star-shaped block copolymers with different molarcompositions. a) Mn,GPC=75,300 g/mol and b) Mn,GPC=26,900 g/mol.
G. D. García-Olaiz, K. A. Montoya-Villegas, A. Licea-Claverie, N. A. Cortez-Lemus. Synthesis andcharacterization of four- and six-arm star-shaped poly(ε-caprolactone)-b-poly(N-vinylcaprolactam): Micellar and core degradation studies. Reactive & Functional Polymers2015, 88, 16-23.
Fig. 6. Hydrodynamic diameter of micellar aggregates determined by DLS at 25 °C (c = 1 mg/mL).
Fig. 7. LCST determined by DLS showingaggregation (samples S(PCL20-b-PNVCL69)4,S(PCL19-b-PNVCL75)6 and S(PCL19-b-PNVCL27)6 ora decrease in the hydrodynamic diameterS(PCL19-b-PNVCL13)6 in the micelle above theLCST.
Fig. 4. Representative images for micellescorresponding to sample S(PCL10-b-PNVCL46)4. a) SEM images of micelles (c =0.013 mg/mL), b) AFM image of a deposit ona mica substrate of an aqueous dispersion ofmicelles (c = 0.02 mg/mL). The solventdisplacement method was used in thepreparation of the micelles.
Fig. 5. AFM images of deposits of aqueousdispersions of micelles obtained from six-armstar(PCL-b-PNVCL) block copolymers on a micasubstrate. a) Sample S(PCL19-b-PNVCL75)6 andb) Sample S(PCL19-b-PNVCL13)6. The solventdisplacement method was used in thepreparation of the micelles.
a) b)
a) b)
Synthesis and characterization of “living” star-shaped
poly(N-vinylcaprolactam) with four arms and carboxylic
acid end-groups
Norma A. Cortez Lemus, Angel Licea-Claverie. J. Polym. Sci., Part A: Polym. Chem., 2016, 54,2156-2165. DOI: 10.1002/pola.28086.
Synthesis of tetra-functional RAFT agent functionalized with carboxylic acid end groups.
RAFT AGENT 1
RAFT AGENT 1
Norma A. Cortez Lemus, Angel Licea-Claverie. J. Polym. Sci., Part A: Polym. Chem., 2016, 54,2156-2165. DOI: 10.1002/pola.28086.
FIGURE 3 FT-IR spectra of a) CTA-1, b) star-shaped PNVCL-COOHpolymers and c) star-shaped S(PNVCL-b-PEHA) copolymers
1.502.002.503.003.504.00
d
d
a
a
b
b
c e
ce
f g
f f
g
ppm
ppm
10.0010.5011.0011.50
h
h
1H NMR spectra (400 MHz) of tetra-functional CTA-1 with carboxylic acid end groups
FIGURE 4 1H NMR (400 MHz) of star-shaped PNVCL-COOH polymers (sample S(PNVCL47)4)
Table 1 Results for RAFT polymerization of NVCL in p-dioxane at 65 ˚C for 36 h in the
presence of CTA-1.a
Entry Sample [NVCL]o: [CTA]o
Conv.b
(%) Mn theor
c Mn GPC
(g/mol)d
Ðe Mn UV-vis
f
1 S(PNVCL18)4 108:1 53 9,200 10,000 1.12 8,800
2 S(PNVCL47)4 246:1 45 16,621 26,000 1.05 21,200
3 S(PNVCL68)4 540:1 49 38,000 38,000 1.15 43,100
4 S(PNVCL94)4 700:1 41 41,100 52,000 1.02 53,500
5 S(PNVCL122)4 900:1 52 64,100 66,300 1.03 84,000
a[NVCL]= 4.8 mol/L.
bDetermined gravimetrically.
cCalculated using eqn Mn theo= MCTA + conversion (MNVCL[NVCL]o/[CTA]o)
d,eBy GPC in THF with RI detector using polystyrene linear standards for calibration and using dn/dc
0.109 (mL/g) for PNVCL.28
fCalculated by end group analysis of UV band (trithiocarbonate absorbance at λ 307 nm, employing ε of the CTA-1).
Norma A. Cortez Lemus, Angel Licea-Claverie. J. Polym. Sci., Part A: Polym. Chem., 2016, 54,2156-2165. DOI: 10.1002/pola.28086.
DLS measurements. Effects of molecular weight on the LCST of star PNVCL-COOH polymers determined by DLS (c = 1 mg/mL).
Norma A. Cortez Lemus, Angel Licea-Claverie. J. Polym. Sci., Part A: Polym. Chem., 2016, 54,2156-2165. DOI: 10.1002/pola.28086.
DLS measurements. Effects of molecular weight on the LCST ofstar PNVCL-COOH polymers (c = 1 mg/mL)
Norma A. Cortez Lemus, Angel Licea-Claverie. J. Polym. Sci., Part A: Polym. Chem., 2016, 54,2156-2165. DOI: 10.1002/pola.28086.
FIGURE 10 Effect of concentration on the LCST of star PNVCL-COOHpolymers (sample S(PNVCL47)4, Table 1, Mn GPC=26,000 g/mol).
Norma A. Cortez Lemus, Angel Licea-Claverie. J. Polym. Sci., Part A: Polym. Chem., 2016, 54,2156-2165. DOI: 10.1002/pola.28086.
ppm0.01.02.03.04.05.0
a
bc,i
d,e,h,j
f
g
a
d
cb
e ee
fg
g
h i
j
k
kkk
k
1H-NMR (400 MHz) spectrum of star-shaped PNVCL-b-PEHA-COOH copolymer in CDCl3
FIGURE 8 DLS measurements (c = 1 mg/mL). Hydrodynamic diameter of S(PNVCL)polymer (Mn GPC=66,300 g/mol) and hydrodynamic diameter of micellar aggregatesfrom S(PNVCL-b-PEHA) copolymer (Mn GPC=69,200 g/mol);
Norma A. Cortez Lemus, Angel Licea-Claverie. J. Polym. Sci., Part A: Polym. Chem., 2016, 54,2156-2165. DOI: 10.1002/pola.28086.
PNVCLPEGPEHA
CTA trithiocarbonate type
N. A. Cortez Lemus and A. Licea-Claverie, Aust. J. Chem. 2017, 70, 1291-1301.
N. A. Cortez Lemus and A. Licea-Claverie, Aust. J. Chem. 2017, 70, 1291-1301.
N. A. Cortez Lemus and A. Licea-Claverie, Aust. J. Chem. 2017, 70, 1291-1301.
N. A. Cortez Lemus and A. Licea-Claverie, Aust. J. Chem. 2017, 70, 1291-1301.
N. A. Cortez Lemus and A. Licea-Claverie, Aust. J. Chem. 2017, 70, 1291-1301.
(PNVCL-b-PEHA-b-PEG)6
PNVCLPEGPEHA
Triblock copolymer Micellar aggregate
N. A. Cortez Lemus and A. Licea-Claverie, Aust. J. Chem. 2017, 70, 1291-1301.
Aggregates in aqueous solution from star (PNVCL-
b-PEHA-b-PEG)6 triblock copolymer
N. A. Cortez Lemus and A. Licea-Claverie, Aust. J. Chem. 2017, 70, 1291-1301.
Figure 12 Drug release from thermoresponsive star polymeric aggregates containing MTX, a) 33 °C and b) 37 °C.
(PVAc-b-(PNVCL-co-PNVP))6
(PNVCL-co-PNVP)6
(PNVCL)6
((PNVCL-co-PNVP)-b-PVAc)6
(PNVCL-b-PVAc)6
Preparation of a Mini-Library of Thermo-Responsive Star(NVCL/NVP-VAc) Polymers with Tailored Properties Using aHexafunctional Xanthate RAFT Agent
Norma A. Cortez Lemus and A. Licea-Claverie, Polymers , 2018, 10 (1), 20
(PVAc-b-(PNVCL-co-PNVP))6
(PNVCL-co-PNVP)6(PNVCL)6((PNVCL-co-PNVP)-b-PVAc)6
(PNVCL-b-PVAc)6
Norma A. Cortez Lemus and A. Licea-Claverie, Polymers, 2018, 10 (1), 20
Scheme 1. Synthesis of hexafunctional star polymers and block copolymers based onPNVCL using a multifunctional xanthate as a RAFT agent.
Figure 2. Dynamic light scattering (DLS) measurements (c = 1 mg/mL in water): (a) effects ofmolecular weight on the lower critical solution temperature (LCST) of star (PNVCL)6 polymers;and (b) evolution of the Dh of the (PNVCL)6 polymers as a function of the temperature.
Norma A. Cortez Lemus and A. Licea-Claverie, Polymers, 2018, 10 (1), 20
Star (PNVCL)6 polymers in aqueous solution: LCST and Dh
Figure 3. DLS measurements. Evolution of the Dh of the star (PNVCL)6 polymers as a function of the molecular weight (c = 1 mg/mL).
Figure 5. 1H-NMR (400 MHz) spectrum of a star (PNVCL-b-PVAc)6 copolymer in CDCl3(Table 2, sample (PNVCL99-b-PVAc21)6, Mn GPC = 94,300 g/mol, Ð = 1.04, 20% of PVAc).
Norma A. Cortez Lemus and A. Licea-Claverie, Polymers, 2018, 10 (1), 20
Star (PNVCL-b-PVAc)6
Figure 6. DLS measurements (c = 1 mg/mL in water) for star (PNVCL-b-PVAc)6 block copolymers:(a) Dh of (PNVCL99)6 and the corresponding (PNVCL99-b-PVAc)6 block copolymers, measured at 20°C; and (b) evolution of the Dh of the (PNVCL99)6 and (PNVCL99-b-PVAc)6 as a function of thetemperature.
Star (PNVCL-b-PVAc)6
Norma A. Cortez Lemus and A. Licea-Claverie, Polymers, 2018, 10 (1), 20
Figure 7. Self-assembly in aqueous solution of star (PNVCL-b-PVAc)6 block copolymers: (a) multiple star micelles; and (b) single flower-like micelle.
Norma A. Cortez Lemus and A. Licea-Claverie, Polymers . 2018, 10 (1), 20
Scheme 3. Synthesis of the star [PVAc-b-(PNVCL-co-PNVP)]6
block copolymers.
Norma A. Cortez Lemus and A. Licea-Claverie, Polymers . 2018, 10 (1), 20
Figure 8. 1H NMR spectrum (400 MHz) in CDCl3 of star-shaped (PVAc-b-(PNVCL-co-PNVP))6
block copolymers. Sample (PVAc30-b-(PNVCL28-co-PNVP17))6, Mn GPC = 42,290 g/mol, Ð = 1.1 (Table 4, Entry 2).
Norma A. Cortez Lemus and A. Licea-Claverie, Polymers . 2018, 10 (1), 20
Figure 9. “Height” image and “3D reconstruction“ from AFM of almost spherical aggregates obtained from six-arm star block copolymers on a mica substrate (c = 0.02 mg/mL): (a,b) Sample (PVAc22-b-PNVCL11)6, Entry 1, Table 4; (c,d) Sample [PVAc30-b-(PNVCL28-co-PNVP17)]6, Entry 2, Table 4; and (e,f) Sample [PVAc17-b-(PNVCL10-co-PNVP7)]6, Entry 3, Table 4.
AFM of almost spherical aggregates from star [PVAc-b-(PNVCL-co-PNVP)]6 block copolymers.
1730 MTX
Sample (PVAc22-b-PNVCL11)6 loaded with MTX
17108C
RMS: 1.16DP = 140 nm
Sample [PVAc30-b-(PNVCL28-co-PNVP17)]6 loaded with MTX
Star [PVAc-b-(PNVCL-co-PNVP)]6 block copolymers.
1766