European Polymer Journal 47 (2011) 486–496

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European Polymer Journal

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Feature Article

Tailoring macromolecular architecture with imidazole functionality: Aperspective for controlled polymerization processes

Matthew D. Green a, Michael H. Allen Jr. b, Joseph M. Dennis a, David Salas-de la Cruz c,Renlong Gao b, Karen I. Winey c,d, Timothy E. Long b,⇑a Department of Chemical Engineering, Macromolecules and Interfaces Institute, Virginia Tech, Blacksburg, VA 24061, USAb Department of Chemistry, Macromolecules and Interfaces Institute, Virginia Tech, Blacksburg, VA 24061, USAc Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USAd Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA

a r t i c l e i n f o a b s t r a c t

Article history:Received 21 July 2010Received in revised form 23 September2010Accepted 24 September 2010Available online 14 October 2010

Dedicated to Professor Nikos Hadjichristidisin recognition of his contribution to polymerscience.

Keywords:ImidazoleControlled radical polymerizationHeterocyclesBlock copolymersLiving polymerization

0014-3057 � 2010 Elsevier Ltd.doi:10.1016/j.eurpolymj.2010.09.035

⇑ Corresponding author. Address: Hahn Hall 2Chemistry (0344), Virginia Tech, Blacksburg, VA 240231 2480; fax: +1 540 231 8517.

E-mail address: telong@vt.edu (T.E. Long).

Open access under CC BY-

Controlled radical polymerization (CRP) allows for the design and synthesis of functionalpolymers with tailored composition and unique macromolecular architectures. Syntheticmethods that are readily available for controlled radical polymerization include nitrox-ide-mediated polymerization, reversible addition–fragmentation chain transfer polymeri-zation, and atom transfer radical polymerization. N-Vinyl monomers that are typicallyamenable to free radical methods are often difficult to synthesize in a controlled mannerto high molecular weight due to the lack of resonance stabilization of the propagating rad-ical. However, recent advances in the field of CRP have resulted in successful controlledpolymerization of various N-vinyl heterocyclic monomers including N-vinylcarbazole,N-vinylpyrrolidone, N-vinylphthalimide, and N-vinylindole. The incorporation of theimidazole ring into homopolymers and copolymers using conventional free radical poly-merization of N-vinylimidazole monomer is particularly widespread and advantageousdue to facile functionalization, high thermal stability, and the relevance of the imidazolering to many biomacromolecules. Copolymers prepared with methyl methacrylatedisplayed random incorporation according to differential scanning calorimetry and amor-phous morphologies according to X-ray scattering. Imidazole- and imidazolium-containingmonomers have shown recent success for CRP; however, the controlled polymerization ofN-vinylimidazole has remained relatively unexplored. Future efforts focus on the develop-ment of tailored imidazole-containing copolymers with well-defined architectures foremerging biomedical, electronic and membrane applications.

� 2010 Elsevier Ltd. Open access under CC BY-NC-ND license.

1. Introduction

Controlled radical polymerization allows for the synthesisof functional copolymers with well-defined architectures,controlled molecular weights, and tunable sequences. Con-

110, Department of61, USA. Tel.: +1 540

NC-ND license.

trolled polymerization reactions typically produce polymerswith predictable molecular weights and narrow polydisper-sity indices (PDI), as well as various architectures unattain-able with conventional free radical techniques, includingstar-shaped and block copolymers. The most widespreadcontrolled polymerizations include nitroxide-mediated radi-cal polymerization (NMP) [1], reversible addition–fragmen-tation chain transfer polymerization (RAFT) [2,3], and atomtransfer radical polymerization (ATRP) [4–6]. The chemistryof N-vinyl monomers presents a fundamental problem for

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their use in controlled polymerizations: the formation of ahighly reactive N-vinyl propagating radical, due to the lackof resonance stabilization, increases the likelihood for chaintransfer and chain termination events. Thus, achieving highmolecular weights, which is desired for optimum thermome-chanical performance, is often challenging. Despite theapparent difficulty for controlled polymerizations, N-vinylheterocyclic monomers have functioned well in controlledradical polymerizations due to recent advances in the fieldas described below (Fig. 1).

Polymers with photoactive applications including pho-tovoltaic devices, photorefractive materials, and photo-copiers typically contain the monomer N-vinylcarbazole(NVC) due to its attractive high hole-transporting capabil-ity and high charge carrier properties [7,8]. Interest in thecontrolled radical polymerization of NVC began with thework of Fukuda et al. [9] who successfully formed NVC-containing block copolymers with styrene using NMP;however, homopolymerization of NVC failed. Later,Schmidt-Naake et al. [10] effectively homopolymerizedNVC using NMP, however, molecular weights proveduncontrollable and narrow polydispersities were not re-ported. The synthesis of a novel NVC block copolymerusing NMP for potential photosensitizer applications,poly(sodium styrenesulfonate-b-NVC), required aceticanhydride as a rate-accelerating additive, but containedonly 5 mol.% NVC [11]. Although the formation of the blockcopolymer occurred successfully, the PDI of the blockcopolymer remained unreported as well as the ability tocontrol molecular weight effectively.

ATRP of NVC led to the first reported homopolymeriza-tion of a narrow PDI (Mw/Mn = 1.33) with C60Cln/CuCl/2,20-bipyridine (bpy) as the catalyst [12]. Ultimately, using a C60

core with multiple initiation sites caused the formation ofstar-like architectures; the size exclusion chromatogramsshowed a bimodal nature, further suggesting the formationof nonlinear architectures. Brar et al. [13] optimized theATRP reaction of NVC with Cu(I)Cl/Cu(II)Cl2/bpy catalystin toluene, which produced the homopolymer in 76% yield.The number-average molecular weight (Mn) versus percentconversion resulted in a linear plot, and the polymers ob-tained exhibited low PDIs (1.01–1.38), suggesting a con-trolled polymerization. Mori et al. [14] demonstratedexcellent control of NVC homopolymerization using RAFTpolymerization methods with xanthate-based chain trans-fer agents. The reported Mn ranged from 3000 to 48,000 g/mol with PDIs between 1.15 and 1.20. This optimized RAFTpolymerization produced poly(NVC) four-arm star poly-mers and amphiphilic star block copolymers for the first

Fig. 1. Structures of N-vinyl heterocyclic monomers a

time, as shown in Scheme 1 [15]. The amphiphilic blockcopolymers consisted of a poly(acrylic acid) star modifiedwith xanthate end groups for subsequent RAFT polymeri-zation with NVC. Due to the success of the controlled poly-merization of NVC, recent publications have focused on thesynthesis of block copolymers to optimize the photosensi-tizing properties of NVC as well as the synthesis of supra-molecular structures for drug delivery applications [16,17].

An additional N-vinyl monomer for use with controlledradical polymerization techniques, N-vinylpyrrolidone(NVP), is attractive for the pharmaceutical, food, and textileindustry industries due to its reported biocompatibility[18,19]. Devasia et al. [20] and Wan et al. [21] first reportedthe controlled polymerization of poly(NVP) using RAFTtechniques. The polymerization of Devasia et al. used adithiocarbamate chain transfer agent and showed pseu-do-first order kinetics with a linear increase in Mn withconversion. Wan et al. chose a xanthate-based chain trans-fer agent dissolved in fluoroalcohol solvents for tacticitycontrol. The results demonstrated narrow PDIs and Mn

showed a linear increase with monomer conversion asshown in Fig. 2. The polymers also contained high syndio-tacticity (60%) due to the use of fluoroalcohol solvents, ver-ifying simultaneous control of molecular weight andtacticity during polymerization. Later studies confirmedxanthates as the chain transfer agent necessary to obtaincontrolled molecular weight and narrow PDIs when homo-polymerizing NVP [22–24]. These studies utilized xan-thate-mediated RAFT polymerization to synthesize novelarchitectures of poly(NVP) forming linear, star, and blockcopolymers. Novel amphiphilic block copolymers formedwith NVP include poly(NVP-b-vinyl acetate)[23,25] andpoly(ethylene glycol-b-NVP) [26]. Targeted applications in-cluded materials for coating catheters or drug encapsula-tion as well as stabilizers in emulsion polymerizations.

Recently, Pound et al. [27] discovered side reactions oc-curred when employing xanthate-mediated RAFT poly-merization, including dimerization of NVP in bulk and insolution. In addition, the NVP unit adjacent to the xanthatemediator underwent elimination at high temperatures(>70 �C). These side reactions affected polymerizationkinetics and molecular weight control, which led to thegrowth of other controlled polymerization methods forNVP. Ray and coworkers demonstrated organostibine-mediated living radical polymerization as a highly effectivemethod to synthesize well-defined poly(NVP) and its blockcopolymers [28]. As shown in Fig. 3, organostibine media-tors resulted in high molecular weight polymers with lowPDIs (1.07–1.29), as well as molecular weight that

vailable for controlled radical polymerization.

Scheme 1. Synthesis of an NVC-containing amphiphilic star block copolymer.

Fig. 2. Mn values (d), Mw/Mn values (N), and SEC curves of poly(NVP) obtained with AIBN/[1-(O-ethylxanthyl)ethyl]benzene in (CF3)3COH at 20 �C under UVirradiation: [NVP]0/[CTA]0/[AIBN]0 (150/1/0.28). Reprinted with permission from [21].

Fig. 3. The effect of NVP concentration in bulk polymerizations on the Mn

and PDI of the resulting homopolymer of NVP using an organostibinemediator and AIBN at 60 �C. Reprinted with permission from [28].

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increased linearly with increasing NVP concentration.Organotellurium- [29] and organobismuthine-mediatedreactions [30] also successfully polymerized NVP in a con-trolled fashion. The PDIs obtained using organotellurium-mediated polymerizations remained lower than the PDIsreported using xanthate-mediated RAFT polymerization.

Another controlled polymerization study utilized forNVP polymerization combined RAFT with either NMP orATRP. Bilalis et al. [31] employed the combination ofNMP and RAFT to form NVP block copolymers containingeither styrene or 2-vinylpyridine. Both methods producedan NVP block with PDIs between 1.4 and 2.2 that wasindicative of a broad molecular weight distribution anduncharacteristic of controlled polymerizations. Hussainet al. [32] combined ATRP and RAFT to synthesize poly(sty-rene-b-NVP). Hussain et al. used ATRP to create the poly-styrene macroinitiator and subsequently converted thebromide endgroup to a xanthate endgroup for the RAFTpolymerization of NVP. The resulting block copolymer

exhibited a PDI of 1.5–1.6 with a Mn of 15,000–16,000 g/mol and formed spherical micelles in aqueous solution. Re-cently, Huang et al. [33] synthesized NVP block copolymerswith styrene or methyl methacrylate (MMA) using RAFTpolymerization of NVP and ATRP of the latter monomerswith a chloroxanthate inifer as shown in Fig. 4. The well-controlled polymerization produced high molecularweight polymers (Mn >50,000 g/mol) with low PDIs (1.3–1.4). This combination of RAFT and ATRP with chloroxant-hate inifers allowed access to a wide variety of monomersto form block copolymers with NVP.

N-Vinylphthalimide (NVPI) and N-vinylindole (NVIn),two additional N-vinyl heterocyclic monomers, have alsoundergone controlled radical polymerization. Numerousbiological, photochemistry, and electroactive polymerapplications incorporate phthalimide and indole groups[34–37]. Most homopolymerization and copolymerizationswith these monomers involved free radical methods. Makiet al. [38] reported the first controlled polymerization ofNVPI following the same methods utilized in the controlledpolymerization of NVP. Xanthate-mediated RAFT polymer-ization produced low molecular weight polymers (Mn

<3700 g/mol, PDI 1.19–1.35). After polymerization,hydrazinolysis in dioxane/methanol deprotected thephthalimide group forming poly(vinyl amine). Thisdemonstrated the feasibility of the controlled polymeriza-tion of a primary amine-containing polymer, allowing forsubsequent modification. The same RAFT method polymer-ized block copolymers containing NVPI and N-isopropylac-rylamide [39] to create an amphiphilic block copolymer.Maki et al. [40] also applied xanthate-mediated RAFT poly-merization to the controlled polymerization of NVIn andits derivatives. As shown in Fig. 5, the polymerization of2-methyl-N-vinylindole proceeded with control of molecu-lar weight and resulted in a polymer having a narrow PDI.

Fig. 4. The synthesis of NVP block copolymers using difunctional haloxanthate inifers under RAFT and ATRP conditions. A bromoxanthate inifer resulted inthe formation of the NVP dimer that led to the use of a chloroxanthate inifer. Reprinted with permission from [33].

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Recently, Chikhaoui-Grioune et al. [41] demonstratedsuccessful RAFT polymerization of NVPI using a thiocar-bonate chain transfer agent. The molecular weight of thepolymer increased linearly with time and exhibited narrowPDIs (<1.2). Electrospinning of this polymer occurred froma DMF solution, and high polymer concentrations(>70 wt.%) were required to obtain uniform, micron-scale(1.2–2.2 lm) fibers.

Recent fundamental developments in controlled radicalpolymerization have accelerated the impact of the N-vinylmonomers discussed above. However, the controlledpolymerization of N-vinylimidazole (NVIm), which is apotentially versatile monomer possessing a nitrogen-con-taining aromatic ring for use in non-viral DNA deliverytherapeutics and in electromechanical actuator materials,currently remains relatively unexplored [42,43]. Conven-tional free radical polymerization of NVIm is extensivelyreported in the literature providing a foundation for stim-uli-responsive polymers with tunable structures throughchemical modification and high thermal stability frommultiple resonance contributors. This manuscript detailsrecent advances in the polymerization of NVIm and the po-tential for emerging applications. Moreover, a perspectivefor the utility of controlled radical polymerization methodsis presented to catalyze future studies in this importantfield.

2. Conventional free radical polymerization of N-vinylimidazole

Previous literature has extensively explored the con-ventional free radical polymerization of NVIm monomers.The isomers, 2-, and 4-vinylimidazole (2VIm and 4VIm,respectively) have received significantly less attention,although they offer resonance stabilization for the propa-gating radical, potentially enabling more controllable poly-merizations. One immediate and prominent differencebetween the monomers is the presence of hydrogen bonddonors in 2VIm (m.p. 128 �C) and 4VIm (m.p. 84 �C). As aresult, these monomers are crystalline solids, whereasNVIm remains a liquid above �50 �C. As observed in ourlaboratory, the homopolymerization of the isomers in solu-

tion is displayed in Scheme 2, and a common solvent is notspecified due to striking solubility differences. The poly-merization of 4VIm becomes heterogeneous as poly(4VIm)precipitates from solution during the reaction. The poly-merization of NVIm however follows pseudo-first orderkinetics as observed using in situ fourier transform infra-red spectroscopy (FTIR), and possesses an observed rateconstant of 1.63 � 10�5 s�1, an order of magnitude fasterthan styrene [44]. We found the resulting polymers offersignificantly different thermal properties. Poly(NVIm) pos-sesses a glass transition temperature (Tg) of 176 �C and athermal degradation temperature of 350 �C or higher,while poly(4VIm) has a Tg of 220 �C, and a Tg for poly(2-VIm) was not observed. The increase in Tg is presumablydue to the hydrogen bonding in poly(4VIm), increasingintermolecular interactions and restricting backbone seg-mental motion. All monomers are protonatable and aretherefore soluble in acidic media, and despite the lack ofamphotericity in NVIm polymers, it remains soluble in ba-sic media similar to 4VIm and 2VIm polymers. 4VIm is syn-thesized through a decarboxylation reaction of urocanicacid, as reported by Overberger et al. [45]. Recently, Ihmet al. [46,47] utilized poly(4VIm) as a potential non-viralgene delivery vector with some success. Others have alsostudied 4VIm due to the pendant imidazole functionalityresembling the amino acid histidine, and the potentialwith regards to non-viral gene delivery and stimuli-responsive behavior related to the amphoteric nature ofimidazole [48]. Lawson et al. [49] reported the synthesisand polymerization of 2VIm, and copolymers preparedwith MMA, acrylonitrile, and styrene. The literature hasyet to explore controlled polymerizations of 2VIm and4VIm.

In our laboratory, investigations into the copolymeriza-tion of NVIm with two monomers separately, n-butyl acry-late (nBA) and MMA have provided insight into thecopolymerization behavior of NVIm. Scheme 3 displaysthe synthetic strategy for the preparation of imidazole-based copolymers with MMA. Conventional free radicalpolymerization yielded the copolymers, which were subse-quently alkylated through a facile SN2 substitution withthe alkyl halide 1-bromobutane. The bromide counteran-ion was subsequently exchanged to the tetrafluoroborate

Fig. 5. (a) Time-conversion (d) and first-order kinetic (j) plots for thepolymerization of 2-methyl-N-vinylindole (2MNVIn) with AIBN in thepresence of O-ethyl-S-(1-phenylethyl)dithiocarbonate (CTA) in 1,4-diox-ane at 60 �C (b) Mn (d) and PDI (j) as a function of conversion. (c)Evolution of SEC traces with conversion. Reprinted with permission from[40].

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Scheme 2. Polymerization of various vinylimidazole isomers (NVIm,2VIm, and 4VIm) using conventional free radical polymerizationmethods.

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(BF4) anion in acetonitrile where NaBr precipitated fromthe reaction. The resulting copolymer was precipitated intowater, and washed copiously to remove excess salt. Thecopolymer composition was analyzed using 1H NMR spec-troscopy, and the thermal properties were determinedusing differential scanning calorimetry (DSC) which exhib-ited a single Tg for the neutral copolymers. We found thecopolymers formed with NVIm and MMA appeared ran-dom, based on their adherence to the theoretical Fox equa-tion that predicts the Tg for random copolymers. Also, thecopolymer composition relative to the feed indicated anearly ideal copolymer system, compared to a specificideal copolymerization where r1 = r2 = 1, with an azeotro-pic monomer feed occurring at 45% NVIm, although the

polymers were obtained at high conversions. Ideal copoly-merization occurs when the product of the reactivity ra-tios, r1 and r2, is equal to one, r1r2 = 1. Fig. 6 displays thecopolymer composition and the Tg as a function of NVImincorporation. However, the copolymers prepared in ourlaboratory with nBA and NVIm did not appear to form ran-dom copolymers. The copolymer composition shifted sig-nificantly relative to the monomer feed ratio, andmultiple, weak, Tg’s were observed using DSC. This behav-ior suggested that NVIm formed more ideal copolymerswith alkyl methacrylates than with alkyl acrylates. Thedetermination of reactivity ratios for these two comono-mers would provide evidence to validate this hypothesis.

We further investigated the morphological properties ofthe NVIm–MMA copolymers and quaternized copolymersusing X-ray scattering over a wide range of scattering an-gles, Fig. 7. The lack of higher order peaks in these scatter-ing profiles indicated completely amorphous morphologiesin both the NVIm–MMA and 1-butyl-3-vinylimidazoliumbromide–MMA (BVIm–MMA) copolymers. For MMAhomopolymers, the primary source of scattering was a re-sult of correlations between neighboring polymer back-bones. The scattering peaks in the uncharged NVIm andcharged BVIm homopolymers correspond to two correla-tion lengths in the amorphous structure, specifically, thedistance between pendant groups along the polymer back-bone at �16 nm�1 and the distance separating the neigh-boring polymer backbones at 4–8 nm�1. Between thesehomopolymers, the amorphous morphologies of thecopolymers vary systematically. As the comonomer(NVIm) content increases in the NVIm–MMA copolymers,the backbone-backbone spacing increases slightly (peaksshift to lower values of nm�1). The increase in the back-bone–backbone spacing is considerably greater for theBVIm–MMA copolymers, because the comonomer ischarged and significantly larger. The pendant–pendantcorrelations are evident between the imidazole functionalgroups in the NVIm–MMA copolymers when the comono-mer content is 80% or higher. The pendant–pendantcorrelations are evident at lower copolymer contents(50%) between imidazolium rings in the BVIm–MMA

Scheme 3. The preparation of MMA–NVIm copolymers with subsequent alkylation and anion exchange.

Fig. 6. The observed copolymer compositions relative to monomer feeds plotted versus a unique case for an ideal copolymerization when r1 = r2 = 1, and Tg

for MMA–NVIm copolymers relative to the Fox equation determined using 1H NMR and DSC.

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copolymers, because the charged comonomers providegreater scattering contrast. In both copolymers, the posi-tion of the pendant-pendant scattering peak is indepen-dent of copolymer composition, because the distance isset by the local p–p stacking of the rings.

3. Perspective for future studies: controlled radicalpolymerization of imidazole-containing monomers

Various sources report the synthesis of NVIm using con-trolled polymerization conditions. Closer analyses of thefindings reveal that the polymerization processes mostlikely do not proceed in a controlled fashion. Liu et al.[50] prepared block copolymers of N-isopropylacrylamide(NIPAm) with NVIm using RAFT conditions obtaining PDIsof approximately 1.2 resulting from the controlled synthe-sis of the NIPAm block. The copolymers displayed uniquesolution properties and formed temperature-dependentmicelles. Endo et al. [51] polymerized NVIm quaternizedwith various substituents, and reported PDIs above 1.26

with molecular weights varying significantly from targetedvalues. Additionally, successful copolymerization with NI-PAm provided seemingly well-controlled block copolymerswith PDIs below 1.4 also attributed to the NIPAm precur-sor. Finally, Nakamura et al. [52] prepared homopolymersof NVIm in a non-traditional manner using UV irradiationof a tellurium-based chain transfer agent, affording con-trolled polymerization with a PDI of 1.14. In our laboratory,homopolymers of NVIm were recently prepared using nitr-oxide-mediated polymerization conditions utilizing Bloc-builder� with number-average molecular weights varyingfrom targeted values as displayed in Fig. 8. The targetedmolecular weights were significantly higher than those ob-served from aqueous size exclusion chromatography mea-surements, and large PDIs (>1.4) indicated a lack of controlover the polymerization process. Also, repeated attemptsat second block addition to form well-defined styreneand nBA multiblock copolymers yielded only startingmaterial.

In addition to controlled polymerization using NMPconditions, our laboratory also investigated anionic

Fig. 7. X-ray scattering of (a) NVIm–MMA copolymers and (b) BVIm–MMA copolymers.

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polymerization as a means of polymerizing NVIm. However,in the presence of anionic initiators such as n-butyllithium,the proton on the C2 position of the imidazole ring wassufficiently acidic for deprotonation, effectively quenchingthe initiator and leading to premature termination. Fig. 9shows a study performed with NVIm in deuterium oxide,where the C2 proton slowly exchanges to deuterium witha half-life of approximately 2.6 h. The acidity of the C2 pro-ton led to premature termination during the anionic poly-merization process.

Although the efforts for controlled radical polymeriza-tion have proven difficult for N-vinylimidazole, recent

Fig. 8. Illustration of nitroxide-mediated polymerization of NVIm and obtaine

literature shows the ionic liquid monomer, 2-(1-butylimi-dazolium-3-yl) ethyl methacrylate tetrafluoroborate(BIMT), possesses imidazolium functionality in amethacrylate monomer for a more controlled radicalpolymerization. Free radical polymerizations of the imi-dazolium–methacrylate monomers did not exhibit controlof molecular weight [53,54]. Ding et al. [55] first polymer-ized BIMT in a controlled fashion using ATRP with a bothCu(I)Br and Cu(I)Cl catalyst. Polymerizations with theCu(I)Br catalyst proceeded rapidly with little molecularweight control, whereas polymerizations with the Cu(I)Clcatalyst showed a linear dependence of molecular weightwith conversion and resulted in polymers with narrowPDIs. RAFT polymerization of the imidazolium-containingmethacrylate derivatives, however, has not shown similarsuccess. Yang et al. [56] first reported RAFT polymerizationof the BIMT monomer to synthesize the block copolymerpoly(N-2-thiazolylymethacrylamide-b-BIMT) for magneticproperty characterization. However, the authors did notperform molecular weight or kinetic analysis to confirmcontrolled polymerization of a novel block copolymer. Vi-jayakrishna et al. [57] reported the synthesis of BIMThomopolymers and other synthetic analogues with RAFTpolymerization as well as block copolymers containingmethacrylic acid. However, the polymerizations proceededslowly (50% conversion required >150 h) and polymeriza-tion kinetics and PDI were not determined for thesecompositions.

Lack of reliable control and the inability to form blockcopolymers under nitroxide-mediated polymerization con-ditions of NVIm led to the investigation of 1-(4-vinylben-zyl)imidazole (VBIm) in our laboratories. This styrenicderivative is readily synthesized from 1-(4-vinylben-zyl)chloride (VBC) [58] and provides propagating radicalstabilities similar to styrene which accommodate facile con-trolled polymerization. This monomer was explored for thepreparation of block copolymers previously, where Shenet al. [59] and Pei et al. [60] investigated the synthesis andpolymerization of the charged monomer – to avoid catalystcoordination – and obtained PDIs below approximately 1.5using ATRP. Waymouth et al. [61,62] also prepared blockcopolymers of VBIm, but used NMP to grow a second blockof VBC from a polystyrene precursor and subsequently func-tionalized with imidazole. These copolymers were investi-gated for their solution behavior and micellar formation insolution. Current research in our laboratory is focused on

d molecular weight data using aqueous size exclusion chromatography.

Fig. 9. Deuterium exchange study of the C2 proton on NVIm to investigate anionic polymerization inhibition.

Scheme 4. Homopolymerization of VBIm using Blocbuilder� to afford nitroxide-mediated polymerization.

Fig. 10. Copolymerization of VBIm and nBA confirmed using 1H NMR spectroscopy and copolymer composition relative to monomer feed plotted versus aunique case for an ideal copolymerization when r1 = r2 = 1, and random incorporation confirmed with Tg’s using DSC which followed the Fox equation.

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the preparation of controlled homopolymers of VBIm. VBImwas polymerized under NMP conditions using the initiatorBlocbuilder�, as shown in Scheme 4. For example, Mn of

20.0 kg/mol was targeted, and a molecular weight of18.3 kg/mol was obtained, as determined using end groupanalysis with 1H NMR spectroscopy.

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Random copolymers of VBIm and nBA were also pre-pared, and the Tg’s for various copolymer compositionswere determined using DSC and 1H NMR, respectively.The Tg’s followed the prediction of the Fox equation, andthe copolymer compositions relative to monomer feed ra-tio display near ideal copolymerization behavior whencompared to a model system where r1 = r2 = 1 as shownin Fig. 10. Random copolymers of styrene and nBA displaynear ideal copolymerization behavior as described previ-ously in literature [63]. Reactivity ratio determination forVBIm–nBA copolymers would provide further insight intocopolymerization behavior.

The design of therapeutic block copolymers using con-trolled radical techniques provides systems with well-de-fined architecture, molecular weight, PDI, and improvedthermal stability. The ability to target specific cells or recep-tors located along the cell membrane is possible throughincorporation of compatible chemical functional groupsthrough sequential monomer addition during controlledpolymerization. Imidazole-containing polymers offer wide-spread impact as non-viral gene delivery therapeutics,though they are typically obtained using free radical poly-merization methods, preventing control of molecularweight and polymer architecture [64]. N-Vinyl monomershave proven difficult to polymerize in a controlled radicalfashion; however, recent advances and synthetic designhave provided feasible methods for controlled architec-tures. We have recently demonstrated the ability to incor-porate the imidazole functionality into block copolymersmaking use of the VBIm monomer for stimuli-responsivematerials. Recent literature has begun to demonstrate thecontrolled polymerization of additional imidazole-contain-ing monomers using NMP, ATRP, and RAFT techniques forthe synthesis of well-defined, high molecular weight poly-mers. Currently, the synthesis of a well-defined N-vinylimi-dazole homopolymer or block copolymer remains elusiveusing these techniques; however, recent fundamental stud-ies have catalyzed the efficient design of functional copoly-mers for many emerging technologies.

Acknowledgements

The authors acknowledge Dr. John M. Layman forinsightful scientific discussions and Arkema, Inc. for theirgracious donation of Blocbuilder� initiator for controlledradical polymerization studies. This material is based uponwork supported in part by the US Army Research Office un-der Grant No. W911NF-07-1-0452 Ionic Liquids in Electro-Active Devices (ILEAD) MURI. This material is also basedupon work supported in part by the Macromolecular Inter-faces with Life Sciences (MILES) Integrative Graduate Edu-cation and Research Traineeship (IGERT) of the NationalScience Foundation under Agreement No. DGE-0333378.

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Matthew D. Green is a Ph.D. candidate inChemical Engineering as a part of the Macro-molecules and Interfaces Institute at VirginiaTech in Blacksburg, Virginia. He earned a B.S.in Chemistry and a B.S. in Chemical Engi-neering in 2007 from Virginia Tech. Matthewis currently coadvised by Dr. Richey M. Davisin the Department of Chemical Engineeringand Dr. Timothy E. Long in the Department ofChemistry at Virginia Tech. He was awarded aNSF IGERT fellowship in 2009 investigatingthe interface between macromolecular struc-

tures and life sciences. His research focuses on the design and synthesis ofcharged imidazolium-containing block copolymers and homopolymers

496 M.D. Green et al. / European Polymer Journal 47 (2011) 486–496

with applications ranging from electromechanical devices to therapeuticdelivery vehicles.

Michael H. Allen, Jr. holds a B.Sc. degree inChemistry, Biology, and Biochemistry fromDeSales University. He is currently a Ph.D.candidate in Chemistry at Virginia Tech inBlacksburg, Virginia. He is currently advisedby Dr. Timothy E. Long. He was awarded anNSF IGERT Fellowship in 2009. His currentresearch focuses on the design and charac-terization of ionic liquid based polyelectro-lytes for biological and material applications.

David Salas-de la Cruz obtained a Bachelor ofScience degree in Chemical Engineering fromthe University of Puerto Rico-Mayaguez and aMaster’s of Science in Chemical Engineeringfrom Villanova University. Currently, he iscompleting a doctorate degree in Chemicaland Biomolecular Engineering at the Univer-sity of Pennsylvania. In 2006 he was appoin-ted President of the Engineering GraduateStudent Council at Villanova University, andin 2007 he was invited to be a member of PhiKappa Phi, the United States’ oldest and most

selective collegiate honor society for all academic disciplines. Over thelast two years he has received the Fontaine Society and the Carl StormUnderrepresented Minority Fellowships, and he serves on the Board of

Directors of the American Institute of Chemical Engineers, DelawareValley. His current research focuses on understanding the fundamentalrelationship between morphology and ionic conductivity in polymerizedionic liquids. He is a renewable energy and biofuels enthusiast. Davidresides in Philadelphia with his wife and young son.

Renlong Gao is currently a graduate studentin the Department of Chemistry at VirginiaTech. He received his B.S. (2007) in polymerchemistry from University of Science andTechnology of China. He is now pursuing hisPh.D. degree in polymer science under thesupervision of Professor Timothy E. Long. Hisresearch interests focus on the synthesis andcharacterization of well-defined ion-contain-ing block and segmented copolymers.

Karen I. Winey is Professor of Materials Sci-ence and Engineering and Chemical and Bio-molecule Engineering at the University ofPennsylvania. Her group designs and fabri-cates polymer nanocomposites containingcarbon nanotubes and metal nanowires withthe aim of understanding how to improvetheir mechanical, thermal, and especiallyelectrical properties. More recently this workhas expanded to include simulations of elec-trical conductivity and polymer dynamics inthe presence of nanoparticles. Winey’s group

has pioneered the use of HAADF STEM to probe the nanoscale morphol-ogy in ion-containing polymers. Now, their effort focuses on correlatingthe structures in these materials, including block copolymers, with

transport properties. She has published over 110 journal articles andholds 5 patents. Winey earned her B.S. in materials science and engi-neering from Cornell University and her M.S. and Ph.D. in polymer scienceand engineering from the University of Massachusetts, Amherst. Herhonors and awards include NSF Young Investigator Award (1994 – 1999),Fellow of the American Physical Society (2003), and NSF Special CreativityAward (2009 – 2011). In addition to serving on various advisory boards,Winey chaired the 2010 Polymer Physics Gordon Research Conferenceand is currently an Associate Editor for Macromolecules and Chair-Electof the Division of Polymer Physics of the American Physical Society.

Timothy Long received his B. S. in 1983 fromSt. Bonaventure University, followed by hisPh.D. in 1987 from Virginia Tech. He spentseveral years as a research scientist at East-man Kodak Company before returning toVirginia Tech as a professor in chemistry. Hehas been a faculty member in the departmentof chemistry since 1998 and recently servedas Associate Director of InterdisciplinaryResearch and Education, Fralin Life ScienceInstitute at Virginia Tech. He serves currentlyas the Associate Dean for Strategic Initiatives

in the College of Science at Virginia Tech. He has received many presti-gious honors in his field of polymer chemistry including the AmericanChemical Society (ACS) Cooperative Research Award in 2011, Virginia

Tech’s Alumni Award for Research Excellence (AARE) in 2010, 2009 ACSFellow, invited organizer of the Gordon Research Conference – Polymers,and Chair, ACS Polymer Division. He has also assembled a successfulinterdisciplinary research group and has been awarded � $30M inresearch funding during his time with Virginia Tech. His group’s contin-uing research goal is to integrate fundamental research in novel macro-molecular structure and polymerization processes with the developmentof high performance macromolecules for advanced technologies.