Synthesis of novel asymmetric dendritic-linear-dendritic block copolymers via “living” anionic polymerization of ethylene oxide initiated by dendritic macroinitiators

Synthesis of Novel Asymmetric Dendritic-Linear-DendriticBlock Copolymers via ‘‘Living’’ Anionic Polymerizationof Ethylene Oxide Initiated by Dendritic Macroinitiators

IVAN GITSOV,1,2 ARSEN SIMONYAN,2 NIKOLAY G. VLADIMIROV3

1The Michael M. Szwarc Polymer Research Institute, College of Environmental Science and Forestry,State University of New York, Syracuse, New York 13210

2Department of Chemistry, College of Environmental Science and Forestry, State University of New York,Syracuse, New York 13210

3Hercules, Inc. Research Center, 500 Hercules Road, Wilmington, Delaware 19808

Received 23 January 2007; accepted 14 June 2007DOI: 10.1002/pola.22258Published online in Wiley InterScience (www.interscience.wiley.com).

ABSTRACT: The first synthesis of asymmetric dendritic-linear-dendritic ABC blockcopolymers, that contain a linear B block and dissimilar A and C dendritic fragmentsis reported. Third generation poly(benzyl ether) monodendrons having benzyl alcoholmoiety at their ‘‘focal’’ point were activated by quantitative titration with organome-tallic anions and the resulting alkoxides were used as initiators in the ‘‘living’’ ring-opening polymerization of ethylene oxide. The reaction proceeded in controlled fash-ion at 40–50 8C affording linear-dendritic AB block copolymers with predictablemolecular weights (Mw ¼ 6000–13,000) and narrow molecular weight distributions(Mw/Mn ¼ 1.02–1.04). The propagation process was monitored by size-exclusion chro-matography with multiple detection. The resulting ‘‘living’’ copolymers were termi-nated by reaction either with HCl/tetrahydrofuran or with a reactive monodendronthat differed from the initiating dendron not only in size, but also in chemical compo-sition. The asymmetric triblock copolymers follow a peculiar structure-induced self-assembly pattern in block-selective solvents as evidenced by size-exclusion chroma-tography in combination with multi-angle light scattering. VVC 2007 Wiley Periodicals, Inc.

J Polym Sci Part A: Polym Chem 45: 5136–5148, 2007

Keywords: anionic polymerization; block copolymers; dendrimers; polyethers; ring-opening polymerization; supramolecular structures

INTRODUCTION

Polymers with hybrid macromolecular architec-tures constructed with flexible and rigid frag-

ments are versatile materials with tunable solu-tion- and solid-state properties.1 The amphiphiliclinear-dendritic copolymers2 that contain poly(ethylene glycol) (PEG) or poly(ethylene oxide)(PEO) are part of this family.3 They may be usedas polymeric surfactants,3(c,d),4 reagents for non-covalent surface-5 and glycoprotein-modification6

or as encapsulating agents.7 The two most fre-quently used methods for the construction ofthese macromolecular PEG hybrids are based on

Dedicated to the 50th anniversary of the discovery of the‘‘living’’ anionic polymerization by Michael M. Szwarc.

Correspondence to: I. Gitsov (E-mail: [email protected])

Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 45, 5136–5148 (2007)VVC 2007 Wiley Periodicals, Inc.

5136

the coupling of preformed reactive monoden-drons onto PEG/PEO3(a,b,d) and on the growth ofthe dendritic block on a linear polyether precur-sor.3(c,e,g,h) With few exeptions,3(j),8 the triblockPEG copolymers reported so far were producedby the first method and all have a symmetricalABA structure with two identical dendritic frag-ments (A) attached to the linear (B) block.

We now report the first approach towards theconstruction of well-defined amphiphilic linear-dendritic copolymers with an ‘‘asymmetric’’ archi-tecture. The synthetic strategy is based on theconsecutive usage of activated monodendrons asthe initiating species for growth of the PEO, fol-lowed by termination of the ‘‘living’’ polymer witha reactive monodendron that differs from the ini-tiating dendron in its size or generation and/orits chemical composition. It is expected that, inselective solvents, the resulting hybrid materialsmight behave differently than their symmetriccounterparts and could also serve as buildingblocks for the covalent and supramolecular con-struction of other hybrid nanostructures withcontrolled architecture and functionality.

EXPERIMENTAL

Materials

The monomer—ethylene oxide (EO) was pur-chased from Aldrich in metal cylinders. It wastransferred via distillation in a sealed burette,dried with n-butyllithium at room temperatureand distilled in a second burette or glass contain-ers with glass break-seals immediately beforeuse. n-Butyllithium (10.0 M solution in hexanes)and NaH (95%, dry) were purchased from Aldrichand used without further purification. Tetrahy-drofuran (THF) (ACS/HPLC certified) and N,N-dimethylformamide (DMF) (HPLC grade) wereobtained from Burdick & Jackson (VWR Scien-tific Products). THF, used as a polymerizationsolvent, was dried by several consecutive distilla-tions over sodium/potassium alloys until it wasable to keep its characteristic blue color. THF,employed as a solvent for the postpolymerizationmodifications, was dried over benzophenone-so-dium. THF used as eluent for size-exclusion chro-matography (SEC) was freshly distilled fromKOH pellets. Potassium, KH and sodium werepurchased from Aldrich. They were rinsed fromthe mineral oil with dry THF in a dry box andfreshly cut immediately before use. Naphtha-

lene–potassium was prepared from recrystallizednaphthalene (Acros Organics, Fisher Scientific),using a previously described procedure.9 Thehexanes (95% n-hexane, Ultra-Resi-Analyzed1)were purchased from J.T. Baker and used asreceived. The reactive poly(benzyl ether) mono-dendrons10 (alcohols – [G-3]-OH,11 and bromides– [G-x]-Br,11 (NC)y[G-z]-Br12 (x ¼ 1–4, y ¼ 2 and4, z ¼ 1 and 2) were synthesized according toknown methods. Deionized water (18.3 MO) wasproduced in a Barnstead Nanopure1 system orin a Milli-Q reverse osmosis station (Millipore)and was used for the SEC—light scatteringanalyses.

Synthetic Procedures

The polymerization of EO initiated by dendriticalkoxides was performed by two different meth-ods. The first one was a classical high-vacuumtechnique in all-glass reaction system withbreak-seals9,13 performed at 50 8C.

The second strategy utilized a Buchi reactor(Buchi, Switzerland), equipped with 1 L stainlesssteel–glass vessel (maximum operating pressure:6 bar) with a bottom valve and three stainlesssteel–glass burettes of 100, 250, and 1000 mL (allwith a maximum operating pressure of 6 bar),propeller stirrer, pressure gauge and pressurerelease valve. Dry compressed nitrogen was usedto maintain the pressure in the reactor vesseland for the transfer of the reagents to the reactor.A typical polymerization procedure was per-formed as follows: The burettes with dry THF,EO, and dry THF solution of the correspondingdendritic bromide were installed on the reactorflange. The reactor was washed with dry THF,vented 10 times with dry nitrogen and pressur-ized to 0.2 bar with dry N2. Dry THF (400 mL)was transferred under nitrogen pressure fromthe THF burette into the vessel, and heated tothe reactor temperature (44 8C). The dendriticalkoxide was formed by quantitative titration ofthe [G-3]-OH with naphthalene–potassium in dryTHF as the medium.13(b) The end of the processwas manifested by the persistence of the typicalolive green color from the last drop of the addednaphthalene–potassium. Alternatively the den-dritic alkoxide could also be formed by reaction of[G-3]-OH with KH taken in 10% molar excess.The resulting clear yellowish solution was trans-ferred via a canula under slight nitrogen pres-sure through one open outlet on the upper reac-tor flange directly to the THF in the reactor

DENDRITIC-LINEAR-DENDRITIC BLOCK COPOLYMERS 5137

Journal of Polymer Science: Part A: Polymer ChemistryDOI 10.1002/pola

under a nitrogen blanket. This transfer was donevery fast to keep moisture away from thereagents and the inner reactor walls. The vesselwas vented again five times with dry nitrogen,closed, pressurized to 1 bar and preheated to44 8C under stirring. A predetermined amount ofmonomer was added at once from the pressurizedEO burette (at room temperature) to the reactorunder vigorous stirring. Under the conditionschosen the polymerization rate was rather slow(more than 12 h for full conversion), enabling amore efficient monitoring of the propagation pro-cess through SEC of small aliquots taken at regu-lar time intervals. Before proceeding with termi-nation of the reaction a final sample was takenfrom the reactor to compare the molecularweights before and after quenching.

The following termination methods of the PEO‘‘living’’ ends were experimented: (a) a slightmolar excess (5%) of a dendritic bromide solutionin THF was added to the polymerization mixturefrom the third burette under pressure; (b) alter-natively the ‘‘living’’ PEO ends were quenched byaddition of 0.1 M HCl in THF.

The polymerization products were isolatedby precipitation from THF into diethyl etherand further purified by two-fold precipitationfrom THF into hexanes. The polymer yieldswere quantitative (97–99%) regardless of thepolymerization method (high vacuum or reactor-based).

The postpolymerization modification of the lin-ear-dendritic AB copolymers obtained after thequenching with HCl/THF was performed with re-active monodendrons with benzyl bromide moietyat their ‘‘focal’’ points [G-x]-Br, (NC)y[G-z]-Br (x¼ 1–4, y ¼ 2 and 4, z ¼ 1 and 2). The reactionwas carried out in dry THF, using previouslyreported procedures.3(a,b)

Instrumentation

SEC with triple detection was performed on asystem consisting of a Waters M510 solvent deliv-ery system, Waters M717 WISP auto sampler,Waters M996 photodiode array UV (PDA-UV)detector, DAWN1 DSP multi-angle laser lightscattering (MALLS) detector (Wyatt Technology),equipped with 30 mWArgon-Ion laser (k ¼ 488 nm)and a Waters M410 differential refractive index(dRI) detector. The separation was achieved on abank of four 300 mm 3 8 mm styrene-divinylben-zene columns (PLgel, Polymer Laboratories) withparticle size 5 lm and pore sizes of 100, 500,

1000, and 100,000 A in THF or DMF at 45 8C.The eluent flow rate was 1 mL/min. The columnswere calibrated with a set of fifteen PEG/PEOand a set of 23 poly(styrene), PSt, standards(both from Polymer Standard Service, USA).

The analyses in a mixed solvent—THF/H2O (1/1 v/v), were performed on the same SEC line out-fitted with two Shodex Protein-PAK columns(KW-802.5 and KW-804, Showa Denko, Japan) at30 8C and eluent flow rate of 1 mL/min. The cali-bration was made with the same PEG/PEOstandards.

Aqueous SEC was carried out on Waters 2690System equipped with Waters M996 PDA-UV de-tector, DAWN1 DSP MALLS detector (WyattTechnology), equipped with 30 mW Argon-Ionlaser (k ¼ 488 nm) and Optilab DSP interfero-metric refractometer (Wyatt Technology) operat-ing at the same wavelength. The separation wascompleted on a set of three 8 lm Aquagel col-umns (OH-30, OH-40 and OH-linear, PolymerLaboratories) in water stabilized with NaN3

(0.02 wt %). The commonly used separation tem-perature was 40 8C unless stated otherwise. Theeluent flow rate was 1 mL/min and the calibra-tion was made with 28 PEG/PEO standards(Tosoh and Polymer Standards Service, USA)with narrow polydispersities and molecularweights ranging from 62 to 885,000 Da.

The determination of the absolute number av-erage molecular weight (Mn) of the copolymerswas performed at room temperature in toluenewith UIC Model 833 vapor pressure osmometer.PEG standards were used for the calibration ofthe instrument.

The refractive index increment (dn/dc) of theAB-, ABA, and ABC linear-dendritic copolymerswas determined in THF, water and THF/water(1/1, v/v) at 30 8C, using the Wyatt Optilab DSPinterferometric refractometer operating at 488nm and DNDC, ver. 5.20 software, from WyattTechnology. The values used in this study were:in THF dn/dc ¼ 0.153 for the [G-3]-PEO AB co-polymers, 0.161 for the [G-3]-PEO-[G-1] ABCcopolymers, 0.190 for the [G-3]-PEO-[G-2] ABCcopolymers and 0.216 for the [G-3]-PEO-[G-3]ABA copolymers; in water dn/dc ¼ 0.123 for the[G-3]-PEO AB copolymers, 0.139 for the [G-3]-PEO-[G-1] ABC copolymers, 0.176 for the [G-3]-PEO-[G-2] ABC copolymers and 0.211 for the [G-3]-PEO-[G-3] ABA copolymers. All values inwater were calculated using concentrationsabove the critical micelle concentration [seeref. 7(a) for details].

5138 GITSOV, SIMONYAN, AND VLADIMIROV


Light scattering experiments were carried outin THF, water and THF/water (1/1, v/v) on theWyatt DAWN1 DSP MALLS detector, describedearlier. Two methods were used: a flow-throughmode (SEC separation and subsequent analysisof the eluting fractions) and a microbatch mode(direct injection of polymer solutions into theinstrument cell). In both cases the molecularweight characteristics and macromoleculardimensions were calculated with Wyatt Technol-ogy ASTRA software (ver.4.7).

The nuclear magnetic resonance (NMR) meas-urements were performed on a Bruker Avanceinstrument (300 MHz) in CDCl3 at room temper-ature with the sample solvent as an internalstandard.

RESULTS AND DISCUSSION

Copolymer Synthesis and Characterization

The reaction temperature of both EO polymeriza-tions (50 8C for the high-vacuum process and44 8C for the reactor process) leads to fast initia-tion, but rather slow propagation as evidenced by

the SEC analysis of reaction mixture aliquotstaken at different polymerization times duringthe reactor process, Figure 1. With the polymer-ization performed in the Buchi reactor on a rela-tively large scale (8–10 g EO) the initiator-mono-mer adduct is still visible at 29.3 min in the SECtraces even after 4.2 h (Fig. 1).

Both the amount of this adduct and the poly-dispersity of the linear-dendritic AB copolymerdecrease with time and approach stable valuesafter 12 h. At the end of the process the amountof unreacted [G-3]-O� in the vacuum polymeriza-tion is below 0.5% of the initial concentration and�1% in the reactor procedure. With both methodsthe polymerization proceeds in a ‘‘living’’ fashionand the molecular weight increases linearly withtime and conversion, the increase being faster inthe high-vacuum experiments (Table 1, Fig. 1).

It could be assumed that the relatively largesize of the dendritic fragment in the initiatingspecies and the use of the potassium counterionprevent the aggregation of the active centers andleads to the formation of copolymers with narrowmolecular weight distributions (Mw/Mn � 1.04).14

It should be mentioned that the higher polydis-persity observed at the early stages of the poly-

Figure 1. Time evolution of the molecular weight distribution of the polymerizationmixtures in the reactor process. SEC eluograms in THF, PDA-UV detection (k ¼ 254nm). (a) time ¼ 1.8 h, Mw ¼ 3100 Da; (b) time ¼ 2.4 h, Mw ¼ 3400 Da; (c) time ¼ 4.2h, Mw ¼ 4900 Da; (d) time ¼ 6.4 h, Mw ¼ 5500 Da; (e) time ¼ 16.6 h, Mw ¼ 8100 Da.[Color figure can be viewed in the online issue, which is available at www.interscien-ce.wiley.com.]



merization (4–8 h, Table 1) is because of the pres-ence of slowly growing initiator species ‘‘contami-nating’’ the aliquots analyzed by VPO (Fig. 1).Notably, the reactor method also requires mono-mer amounts above 6 g to yield polymers withpredictable molecular weights and narrow molec-ular weight distributions. When the monomerconcentration is lower the molecular weight ofthe polymers formed tends to be higher than thepredicted, due most probably, to the quenching ofsome active centers by traces of moisture thatcould not be fully eliminated. These sampleswere not further investigated. It should beemphasized, that the copolymers discussed in thefollowing sections do not contain notableamounts of PEO homopolymer that could be pro-duced by KOH traces formed by eventual mois-ture. This is confirmed by SEC with double dRI/PDA-UV detection where full coincidence of bothdetector traces is observed in THF, water andtheir mixture.

The desired ABC copolymer can be producedby a direct termination of the ‘‘living’’ alkoxideends with dry THF solutions of different dendri-tic bromides of the same (third) or different gen-eration (first, second and fourth). A deficiency ofthis approach is the necessity to add the ‘‘living’’polymer to an excess of the corresponding bro-mide. Since there is no visible color change theend of the titration is hard to detect. In the vac-uum polymerization, where the concentration ofthe active centers could be calculated from theamount of initiator, adding an exact volume of‘‘living’’ polymer solution to the dendritic bromideis not straightforward, as well. Alternatively thesame product could be obtained by a traditionalquenching of the system with HCl/THF and

a subsequent modification of the isolated AB co-polymer via the previously used Williamson ethersynthesis, Scheme 1.3(a)

This approach requires precise determinationof the copolymer molecular weight to ensure thestoichiometric balance of all subsequent modifica-tion reactions, an issue that will be discussed inthe following section. In both procedures theattachment of the second dendritic fragment (C)proceeds quantitatively when unsubstituted ben-zyl ether dendritic bromides are used. The excessof quenching agent(s) is removed by a threefoldprecipitation from THF into acetone/methanol(1:3 v/v). The yields after the purification precipi-tations are 94–98%. The 1H NMR analysis showsthe typical signals, characteristic for the dendri-tic fragment(s) (d, ppm: 4.52; 4.94; 5.03; 6.54–6.57; 6.65–6.70; 6.81; 7.22–7.40)3(a,b) and thePEO block (d, ppm: 3.60–3.70).3(a,b) In the case ofcyano-terminated dendrons notable amounts ofgel-like side products (12% for (NC)2[G-1]-Br and27% for (NC)4[G-2]-Br) were formed, perhaps dueto a competing reaction of the peripheral CNgroups with the NaH used in the Williamsonether reaction.15 An evidence for the participa-tion of the cyano-groups in these reactions is thedisappearance of the signal for the CN carbonatom at 118.51 ppm in the 13C NMR spectra ofthe side products.12 The same signal is clearlyvisible in the spectra of the purified ABC copoly-mers along with the signals characteristic for thedendritic fragments (d, ppm: 69.0, 69.7, 101.7,102.2, 106.45, 108.1, 111.8, 127.4, 132.3, 139.8,139.45, 142.0, 159.6 and 159.7) and the PEOchain (d, ppm: 70.3 and 71.3).

As previously mentioned, knowledge of theexact molecular weight of the linear-dendriticprecursor is an important factor, used to helpensure the quantitative formation of the asym-metric triblock copolymers. Earlier studies haveshown that MALDI-TOF is a suitable techniquefor the precise determination of the molecularweight characteristics and end-group structure oflinear-dendritic copolymers containing PEGblocks.16 Regrettably the precision and the reso-lution power of this method are reported to dete-riorate rapidly with molecular weights above10,000 Da.16(b) The same tendency is alsoobserved in this investigation and therefore thismethod is not capable of providing reliableresults in this molecular weight region. Conven-tional SEC analysis reveals the narrow molecularweight distribution of the starting dendritic frag-ments [Fig. 2(A)] and of the copolymers that are

Table 1. High-Vacuum Polymerization of EO,Initiated by [G-3]-O�Kþ in THF at 50 8C

Time (h)Conversiona

(%) Mnb (Da) Mw/Mn

c

0 0 1591d 1.014 37 3700 1.128 63 6200 1.08

12 93 9200 1.04

[EO]/[G-3]O� ¼ 225.a Determined gravimetrically.b Measured by vapor-pressure osmometry, see ‘‘Experi-

mental’’ section for details.c Obtained by SEC in THF, see ‘‘Experimental’’ section for

details.d Molecular weight of the dendritic macroinitiator.



Scheme 1. Synthetic route to an ABC copolymer via vacuum- or reactor formationof AB copolymer and postpolymerization coupling of the C block. [Color figure can beviewed in the online issue, which is available at www.interscience.wiley.com.]



formed [Fig. 2(B)], but shows notable differencesin the calculated molecular weight values de-pending on both the solvent (THF or DMF) andthe calibration standards used (PST or PEG/PEO), Table 2.

In fact the trace of the initial AB copolymer(produced by the reactor polymerization) is notdistinguishable from the eluograms of the ABC

copolymers formed by the postpolymerizationmodification of the same AB copolymer [Fig. 2(B)]despite the incorporation of dendritic fragmentsof vastly different sizes [Fig. 2(A)]. The sym-metric ABA copolymers of similar composition([G-x]-PEG2k-[G-x], [G-x]-PEG5k-[G-x] and [G-x]-PEG11k-[G-x], x ¼ 1–3) behave similarly inTHF.4 Obviously the linear portion of the random

Figure 2. SEC eluograms of reactive monodendrons (A) AB diblock- and (B) ABCtriblock copolymers. Eluent—THF, PDA-UV detection (k ¼ 254 nm). See ‘‘Experimen-tal’’ section for analysis conditions. A: Dendritic bromides [G-1]-Br (1), [G-2]-Br (2), [G-3]-Br (3), and [G-4]-Br (4). B: Linear dendritic AB copolymer, [G-3]-PEO13k (1), ABC co-polymer [G-3]-PEO13k-[G-1] (2), ABC copolymer [G-3]-PEO13k-[G-2] (3), ABA copoly-mer [G-3]-PEO13k-[G-3] (4), ABC copolymer [G-3]-PEO13k-[G-4] (5). AB copolymerwas produced by the reactor procedure and the ABC, and ABA copolymers were formedby postpolymerization modification with the corresponding reactive monodendron. [Colorfigure can be viewed in the online issue, which is available at www.interscience.wiley.com.]



coils of the hybrids, which is the same for all fourcopolymers presented in Figure 2, is the majorcontributing factor to their apparent contoursize, a key element in the size-exclusion mecha-nism.

On the other hand the classical methods fordetermination of absolute molecular weights –vapor pressure osmometry (Mn) and light scatter-ing (Mw) produce mutually supportive andreliable values not only for the linear-dendriticprecursor, but also for the ABC copolymers. Anexample is shown in Table 3, where the calcu-lated Mn and Mw for [G-3]-PEO13k-[G-4] are inreasonable agreement with the theoretically pre-dicted value (Mth ¼ 17,475 Da, based on the ini-tial Mn of the linear-dendritic precursor-[G-3]-PEO13k).

Solution Behavior

All block copolymers exist as monomolecular spe-cies with rather similar hydrodynamic volumesin DMF and THF (Fig. 2), both being relativelygood solvents for the linear- and the dendritic-blocks. There is no apparent difference in thebehavior of [G-x]- and (NC)y[G-z]-terminatedABC copolymers.

In water, a selective solvent for the linear PEOblock, all copolymers (both AB-, ABA-, and ABCstructures) self-assemble even at very low con-

centrations that are close to the detection limitsof the SEC detectors, Figure 3. It should be men-tioned that the observed supermolecules persis-tently form in sizes and molecular weights thatare strictly dependent on the generation of thesecond dendritic block. For example, in water thelinear-dendritic AB copolymer [G-3]-PEO13k,shown in Figures 2(B), 1 and 3, 1, forms a single-population of micelles with Mw ¼ 2,183,0006 7000 Da and Rg ¼ 58 6 1.4 nm as measured bymulti-angle light scattering analysis in the samemedium, Figure 4. When these values are com-pared with the previously reported data for asymmetric triblock copolymer with the same-gen-eration dendrimers and only slightly shorter PEGchain – [G-3]-PEG11k-[G-3] (Mw ¼ 13,300,000 Daand Rg ¼ 44 nm7(a)) an apparent discrepancybetween the molecular weight and the radius ofgyration for the AB and the ABA copolymers isimmediately noticeable. It could be, however, eas-ily explained with the obvious necessity for a loopformation in the linear PEG block of [G-3]-PEG11k-[G-3] during the collapse of the hydro-phobic [G-3] monodendrons into the micellarcore. This process would effectively reduce theoverall size (Rg) of the resulting supermoleculeseven at higher aggregation numbers.

It would be interesting to explore the pertur-bations of the linear-dendritic hybrids in a envi-ronment that would be both selective and nonse-

Table 2. Number Average Molecular Weights (Mn) of the Linear-Dendritic Precur-sors [G-3]-PEO Obtained by SEC with Different Solvents/Standards

SampleaTHF/PEG,Mn (Da)

THF/PSt,Mn (Da)

DMF/PEG,Mn (Da)

DMF/PSt,Mn (Da)

A 7500 10,600 7300 27,800B 7700 10,700 9200 34,100C 19,200 6000 16,400 56,800

a Produced by reactor polymerization.

Table 3. Molecular Weight Characteristics of [G-3]-PEO and [G-3]-PEO-[G-4]Calculated by Size Exclusion Chromatography (SEC), Vapor-Pressure Osmometry(VPO), and Multi-Angle Laser Light Scattering (MALLS)

Sample Mn (SEC)a Mn (SEC)b Mn (VPO) Mw (MALLS)

[G-3]-PEOc 17,000 18,700 14,200 6 500 14,900 6 600[G-3]-PEO-[G-4]d 15,400 17,400 18,400 6 700 18,700 6 400

a Calculations made with PEG/PEO calibration.b Calculations made with PSt calibration.c Formed by vacuum polymerization.d Produced in vacuum by quenching of the ‘‘living’’ [G-3]-PEO precursor with [G-4]-Br.



lective for the dendritic fragments and the PEOportion. A mixture THF/H2O (1/1 v/v) seems likea suitable medium: the THF is a good solvent forthe poly(benzyl ether) dendrimers and relativelypoor solvent for a PEO block of this length,whereas water dissolves freely the PEO and pre-cipitates the dendrimers. In this mediumthe same AB copolymer [G-3]-PEO13k generatesmonodisperse micelles with larger size (Rg ¼ 1576 5 nm), but lower molecular weight (Mw

¼ 568,000 6 3800 Da), Figure 5.At first glance the molecular weight and the

size of the supermolecules, formed by this copoly-mer in this mixed solvent are in drastic discrep-ancy with the values obtained in pure water. Onehas to take into account, however, that the core-forming dendritic moieties have much better sol-ubility in THF/H2O than in H2O, which wouldultimately lead to lower aggregation numbers(lower molecular weight of the micelle). Theimproved solubility would also reduce the com-pactness of the micelles and would lead toincrease in the core- and corona sizes (higher Rg

values). This assumption is further supported by

the increase of the second virial coefficient A2 ofthe [G-3]-PEO13k supermolecules with theswitch from pure water to the mixed medium.The measured value in water is (3.784 6 0.074)3 10�5 mol 3 mL 3 g�2, whereas the value inTHF/H2O is much higher (1.2 6 0.072) 3 10�2

mol 3 mL 3 g�2 (Figs. 4 and 5). The observed dif-ference is well above the molecular weight de-pendence of A2

17 and represents a clear indica-tion for the increased interaction between thepolymer and the surrounding medium. The pro-nounced curvature in the Zimm diagrams (Figs. 4and 5) is not an uncommon phenomenon. It istypically associated with species of extremelyhigh molecular weights or sizes (see, e.g., ref. 17,p 174). In our case it also hints on the existenceof asymmetric density distribution across themicellar profile because of the more compact den-dritic core and the more loose linear shell organi-zation.18,19

The same solvent differentiation is observedwith the asymmetric triblocks. Figure 6 showsthe elution profiles and the molecular weights ofthe separated fractions for [G-3]-PEO13k-[G-2]

Figure 3. Aqueous SEC eluograms of linear-dendritic diblock- and triblock-copoly-mers at low concentrations (<0.5 mg/mL, 0.2 mL injection volume).PDA-UV detection (k ¼ 254 nm). See ‘‘Experimental’’ section for analysis conditions.Linear dendritic AB copolymer (ld_1), [G-3]-PEO13k (1), ABC copolymer (G3G1H), [G-3]-PEO13k-[G-1] (2), ABC copolymer (g3g2h), [G-3]-PEO13k-[G-2] (3), ABA copolymer(g3g3h), [G-3]-PEO13k-[G-3] (4), ABC copolymer [G-3]-PEO13k-[G-4] is not com-pletely water-soluble and is not shown. AB copolymer was produced by the reactorprocedure and the ABC, and ABA copolymers were formed by postpolymerizationmodification with the corresponding reactive monodendron. [Color figure can beviewed in the online issue, which is available at www.interscience.wiley.com.]



obtained by SEC-MALLS in water (blue trace)and THF/H2O (1/1 v/v, red trace). The aqueouschromatogram reveals the presence of multiplepoorly resolved micellar fractions with molecu-lar weights between 1.1 3 106 Da and 1.1 3 105

Da eluting between 10.5 and 12.5 mL, respec-tively. In sharp contrast, the mixed THF/H2Ophase contains two well separated fractions thatelute at 11.25 and 15.75 mL. The large disparityin their hydrodynamic volumes is noticeable,

but remarkably, their molecular weights arein the same range—between 7 3 105 Da and8 3 105 Da.

Qualitatively the observed phenomenon couldbe explained by the existence of two differentsupermolecules that contain similar number ofunimers, but have different supramolecular orga-nization as illustrated in Scheme 2. Obviouslythe size (i.e., hydrodynamic volume) of structureB, in which all dendritic fragments have col-

Figure 4. Light scattering of the linear-dendritic copolymer [G-3]-PEO13k in H2O,see ‘‘Experimental’’ section for analysis and calculation conditions. [Color figure canbe viewed in the online issue, which is available at www.interscience.wiley.com.]



Figure 6. Relationship of the molecular weight (molar mass, g/mol) and elution vol-ume (volume, mL) for asymmetric ABC triblock copolymers [G-3]-PEO-[G-2] revealedby SECMALLS in pure water (two Aquagel columns: OH-30 and OH-40) - blue trace(G22PGW1), and THF/water (1/1 v/v) - red trace (G22PG5TF). MALLS 908 detectorsignal, see ‘‘Experimental’’ section for analysis conditions. [Color figure can be viewedin the online issue, which is available at www.interscience.wiley.com.]

Figure 5. Light scattering of the linear-dendritic copolymer [G-3]-PEO13k in amixed solvent THF/H2O (1/1 v/v), see ‘‘Experimental’’ section for analysis and calcu-lation conditions. [Color figure can be viewed in the online issue, which is available atwww.interscience.wiley.com.]



lapsed in the core would be smaller, because ofthe loop formation by the solubilizing PEO block.Structure C would be more voluminous becausethe smaller [G-2] fragments could be partiallyenveloped by the sufficiently long and extendedPEO chains and remain outside of the micellarcore. The possibility for the occurrence of suchstructures in a different mixed medium (metha-nol/water ¼ 1/1 v/v) was suspected in our previ-ous papers for hybrids with the similar buildingblocks and linear or star-like construction.3(d),4

However, the first evidence for their existence isprovided in this study by the combined SEC-MALLS analysis of the asymmetric dendritic-lin-ear-dendritic copolymer [G-3]-PEO13k-[G-2].

The existence of two distinct fractions fromthe same amphiphilic copolymer was alsoreported by Gnanou and coworkers for their poly-(styrene)-block-PEO copolymers in THF andwater.14

CONCLUSIONS

The results obtained show that the ‘‘living’’ ani-onic polymerization of ethylene oxide, initiatedby dendritic poly(benzyl ether) alkoxides can pro-duce linear-dendritic copolymers with controlledmolecular weights and narrow polydispersities.Importantly the procedures we use for the prepa-

ration of these materials under inert atmospherecan be scaled-up easily thus enhancing theirapplication potential. This process allowed us tosynthesize for the first time new asymmetric den-dritic-linear-dendritic copolymers, which differfrom the corresponding symmetrical nanoscaleobjects in their solution properties. In this studywe have employed Williamson ether reaction forthe formation of block copolymers, where theasymmetry and the unusual self-assembly pat-terns were induced mainly by the size (genera-tion) of the second monodendron and not by theperipheral functionalities therein. The presenceof the hydroxyl end group in the initial AB pre-cursor, however, offers many more modificationopportunities through a broad palette of chemis-tries and reactive monodendrons of differentcomposition.

Financial support of this research by the US Depart-ment of Agriculture (McIntire-Stennis Award) andNSF (MCB-0315663) is acknowledged with thanks.The authors also thank D. Yu (UC Berkeley) and C.Zhu (SUNY ESF) for their assistance in the earlystages of the investigation.

REFERENCES AND NOTES

1. (a) Frechet, J. M. J. Science 1994, 263, 1710; (b)Roovers, J.; Comanita, B. In Advances in Polymer

Scheme 2. Structure-induced self-assembly of ABC triblock copolymer [G-3]-PEO13k-[G-2] in THF/H2O.



Science; Roovers, J., Ed.; Springer Verlag: Berlin,1999; Vol. 142, p 179; (c) Ishizu, K.; Tsubaki, K.;Mori, A.; Uchida, S. Prog Polym Sci 2003, 28, 27;(d) Hawker, C. J.; Wooley, K. L. Science 2005,309, 1200.

2. For a review on these hybrid copolymers see: Git-sov, I. In Advances in Dendritic Macromolecules;Newkome, G. R., Ed.; Elsevier: Amsterdam, 2002;Vol. 5, pp 45–87.

3. For representative examples see: (a) Gitsov, I.;Wooley, K. L.; Frechet, J. M. J. Angew Chem IntEd 1992, 31, 1200; (b) Gitsov, I.; Wooley, K. L.;Hawker, C. J.; Ivanova, P. T.; Frechet, J. M. J.Macromolecules 1993, 26, 5621; (c) Chapman,T. M.; Hillyer, G. L.; Mahan, E. J.; Shaffer, K. A.J Am Chem Soc 1994, 116, 11195; (d) Gitsov, I.;Frechet, J. M. J. ibid 1996, 118, 3785; (e) Iyer, J.;Fleming, K.; Hammond, P. T. Macromolecules1998, 31, 8757; (f) Iyer, J.; Hammond, P. T. Lang-muir 1999, 15, 1299; (g) Chang, Y.; Kwon, Y. C.;Lee, S. C.; Kim, C. Macromolecules 2000, 33,4496; (h) Gitsov, I.; Lambrych, K. R.; Ivanova,P. T.; Lewis, S. Polym Mater Sci Eng 2001, 84,925; (i) Ihre, H.; Padilla de Jesus, O. L.; Frechet,J. M. J. J Am Chem Soc 2001, 123, 5908; (j) Ihre,H. R.; Padilla De Jesus, O. L.; Szoka, F. C., Jr.; Fre-chet, J. M. J. Bioconjugate Chem 2002, 13, 443; (k)Gillies, E.; Frechet, J. M. J. J Am Chem Soc 2002,124, 14137; (l) Lambrych, K. R.; Gitsov, I. Macromo-lecules 2003, 36, 1068; (m) Gillies, E.; Frechet,J. M. J. J Org Chem 2004, 69, 46; (n) Namazi, H.;Adeli, M. J Polym Sci Part A: Polym Chem 2005,43, 28; (o) Broeren, M. A. C.; Linhardt, J. G.;Malda, H.; de Waal, B. F. M.; Versteegen, R. M.;Meijer, J. T.; Lowik, D. W. P. M; van Hest, J. C. M.;van Genderen, M. H. P.; Meijer, E. W. J Polym SciPart A: Polym Chem 2005, 43, 6431; (p) Namazi,H.; Adeli, M. Polymer 2005, 46, 10788; (q) Santini,C. M. B.; Hatton, T. A.; Hammond, P. T. Langmuir2006, 22, 7487; (r) Hietala, S.; Nystrom, A.; Tenhu,H.; Hult, A. J Polym Sci Part A: Polym Chem 2006,44, 3674; (s) Adeli, M.; Haag, R. J Polym Sci PartA: Polym Chem 2006, 44, 5740.

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10. A monodendron is broadly defined as a perfectlybranched, convergently or divergently grown mac-romolecule, with multiple surface groups and asingle reactive functionality at its ‘‘focal’’ point. Inthis article we use the following abbreviation forthe reactive monodendrons: [G-x]-OH and [G-x]-Br denote poly(benzyl ether) monodendrons withbenzyl alcohol and benzyl bromide group at theirfocal point, respectively. (NC)y[G-z]-Br stands forcyano-terminated poly(benzyl ether) monoden-drons with benzyl bromide group at their focalpoint. In all cases x and z are the generationnumbers (x ¼ 1–4; z ¼ 1–2).

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19. It should also be mentioned that the read headangle in the DAWN1 DSP instrument in water is328 (see DAWN1 Hardware Manual, Appendix G,Table G-6, Wyatt Technology Co.), not sufficientlylow to suppress the curvature in the scatteringdiagram.



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Synthesis of novel asymmetric dendritic-linear-dendritic block copolymers via “living” anionic polymerization of ethylene oxide initiated by dendritic macroinitiators