Synthesis and Postfunctionalization of Well-Defined Star Polymers via ‘‘Double’’ Click Chemistry

Synthesis and Postfunctionalization of Well-Defined Star Polymersvia‘‘Double’’Click ChemistryCyrille Boyer,Michael Whittaker,Thomas P.DavisSchool of Chemical Engineering,Centre for Advanced Macromolecular Design(CAMD),The University of New South Wales, 2052NSW,Sydney,AustraliaCorrespondence to:C.Boyer(E-mail:cboyer@.au)Received11August2011;accepted8September2011;published online4October2011DOI:10.1002/pola.25001ABSTRACT:In this article,the synthesis and the functionaliza-tion of well-defined,narrow polydispersity(polydispersity index<1.2)star polymers via reversible addition-fragmenta-tion chain transfer polymerization is detailed.In this arm first approach,the initial synthesis of a poly(pentafluorophenyl ac-rylate)polymer,and subsequent,cross-linking using bis-acryl-amide to prepare star polymers,has been achieved by reversible addition fragmentation chain transfer polymeriza-tion.These star polymers were functionalized using a variety of amino functional groups via nucleophilic substitution of pentafluorophenyl activated ester to yield star polymers with predesigned chemical functionality.This approach has allowed the synthesis of star glycopolymer using a very simple approach.Finally,the core of the stars was modified via thiol-ene click chemistry reaction using fluorescein-o-acrylate and DyLigh633Maleimide.V C2011Wiley Periodicals,Inc.J Polym Sci Part A:Polym Chem49:5245–5256,2011KEYWORDS:activated ester,click chemistry,functionalization of polymers;radical polymerization;reversible addition fragmen-tation chain transfer polymerization(RAFT),star polymer, thiol-ene.INTRODUCTION Star polymers have attracted a lot of research interests due to their unique solution properties in particular their relationship between arm number,arm mo-lecular weight and solvent viscosity.1–4Star polymers can be seen as singular well-defined and structurally complex nano-particles which have found applications in nanomedicine,5–8 catalyst,9and in photonics.10,11In general well-defined star polymers have been prepared via two different routes;arm first approach or core first approach.In the core first approach,the synthesis of a suitable macroinitiator bearing a defined number of initiating groups is used to obtain star polymers.The approach was initially demonstrated using ionic polymerization techniques which are ideally suited to this star syntheses procedure as bimolecular termination (especially coupling)is not present,and therefore star–star coupling by-products are not produced.12–14With the later discovery of living radical techniques,all three main syn-thetic methods,viz,atom transfer radical polymerization (ATRP)/metal mediated,15–21RAFT/MADIX,22–29and NMP,30 have been exploited to make multiarm star polymers using this approach.However all these mechanisms suffer from radical intermediate termination reactions,and therefore,the optimization of the reaction conditions to minimize these becomes an important consideration for generating narrow polydispersities(an issue of particular importance in nano-medicine applications).5,31,32In the unique case of RAFT polymerization,the star–star coupling problem can be addressed in a limited fashion by using a Z-group approach rather than a R-group approach to arm growth.24Although this approach minimizes star–star coupling the chain growth process is still vulnerable to solvent and monomer accessibil-ity problems,as was shown in theoretical and experimental work.33–35To obviate these problems the alternate‘‘arm-first’’method can be implemented;where presynthesized arms are either attached to a suitable multifunctional core or linked itera-tively together to form a star(usually through cross-linking chemistry to give a cross-linked core).However in both these cases at higher arm molecular weights and arm numbers, steric effects generally come into play and less than quantita-tive yields are achieved.36With the emergence of‘‘click chemistry,’’both Huisgen cycloaddition and thiol-ene have been used to connect cores to arms negating any radical ter-mination problems.37–41Multifunctional microgels or nano-gels have also proved to be suitable cores for polymer stars. These cores can be synthesized via cross-linking polymeriza-tion chemistry and any residual vinyl groups used for subse-quent arm attachment.The iterative linking together of poly-mer arms via cross-linking chemistry has been applied to living radical polymerization,and been optimized for ATRP initially by Matyjaszewski17and expanded on by Qiao and coworkers who both reported very narrow polydispersitiesV C2011Wiley Periodicals,Inc.using ATRP.42–44Using RAFT polymerization however the generation of polymer stars with narrow polydispersities has remained elusive(as exemplified by previous work45).How-ever,we have recently shown that by judicious choice of both cross-linker and solvent,narrow polydispersity polymer stars can be routinely achieved in high yield and in a facile manner via the RAFT process.In this work,we prepared star polymers bearing activated ester groups,via an arm first methodology.Arm polymers were first prepared via RAFT polymerization of pentafluoro-phenyl acrylate(PF-A).PF-A is an activated ester monomer developed by Theato and coworkers,46–49(with similar reac-tivity to N-hydroxysuccinimide).PF-A based polymers have been extensively used to react with functional amine com-pounds and to introduced functional side-groups into linear polymer molecules with a very high yield.50–55In our previ-ous work,we exploited PF-A chemistry to synthesize linear glycopolymers,56and to cross-link polymeric nanoparticles.57 In this work,activated ester chemistry has been exploited to attach a variety of functional amino compounds to stars giv-ing rise to a library of functional,well-defined polymer stars in high yield.To the best of our knowledge,it is the first time such functional star polymers have been obtained using this ing this approach,we are able to prepare a variety of glycopolymer star using a very simple methodology.EXPERIMENTALMaterialsThe initiator,2,20-azobisisobutyronitrile(AIBN),was crystal-lized twice from methanol.DyLigh633Maleimide Dye was provided by Thermo Scientific.All the others chemical reac-tants were purchased from Sigma-Aldrich,supplied at the highest purity available.High purity N2(Linde gases)was used for reaction solution purging.Membranes for dialysis (regenerated cellulose tubular membrane,diameter12.1 mm)MWCO¼3500,6000,and12,000–14,000Da)were provided by Fisher Biotec Australia and Membrane Filtration Products.AnalysesGel Permeation Chromatography(GPC)Measurements DMAc GPC analyses of the polymers were performed in N,N-dimethylacetamide[DMAc;0.03%w/v LiBr,0.05%2,6–di-butyl-4-methylphenol(BHT)]at50 C(flow rate¼1mL minÀ1)using a Shimadzu modular system comprised of an SIL-10AD autoinjector,a PL5.0-mm bead-size guard column (50Â7.8mm)followed by four linear PL(Styragel)col-umns(105,104,103,and500Å)and an RID-10A differential refractive-index detector.Calibration was achieved with commercial polystyrene standards ranging from500to106 g/mol.THF GPC analyses were performed on a Shimadzu modular system,comprising an autoinjector and a Polymer Laboratories5.0l m bead size guard column(50Â7.5mm), followed by three linear PL column and a differential refrac-tive index detector using THF as the eluent at40 C with a flow rate of1mL minÀ1.The GPC system was calibrated using linear polystyrene standards.Nuclear Magnetic Resonance(NMR)Structures of the synthesized compounds were analysed by 1H NMR spectroscopy using a Brucker DPX300spectro-meter at300MHz for hydrogen nuclei,282MHz for fluor nuclei and75MHz for carbon nuclei.The monomer(PF-A)and cross-linker conversion was calcu-lated using19F NMR and1H NMR:(i)PF-A conversion calcu-lated by19F NMR analysis and using the following equation: a FP-A¼[$À158.0ppm/($IÀ158.0ppmþ$À152.5ppm)]Â100,with $À158.0ppm and$IÀ158.0ppm corresponding to integral of thesignal atÀ158.0and atÀ152.5ppm,respectively;(ii)cross-linker conversion calculated by1H NMR analysis and using the following equation:a cross-linker¼(5Â$I5.5–6.5ppm)/(3Â$I7.2ppm)Â[RAFT]0/[Cross-linker]0Â100,with[RAFT]0, [Cross-linker]0,$I5.5–6.5ppm and$I7.2ppm corresponding to cross-linker and RAFT end group concentration,integral of the signal at5.5–6.5ppm and at7.2ppm,respectivelyUV-Visible SpectroscopyUV-visible spectra were recorded using a CARY300spectro-photometer(Bruker)equipped with a temperature controller.Dynamic Light Scattering(DLS)DLS measurements were performed using a Malvern Zeta-sizer Nano Series running DTS software and using a4mW He A Ne laser operating at a wavelength of633nm and an avalanche photodiode(APD)detector.The scattered light was detected at an angle of173 .The temperature was sta-bilized to60.1 C of the set temperature.To reduce the influence of larger aggregates the number-average hydro-dynamic particle size is reported.The polydispersity index (PDI)is used to describe the width of the particle size distri-bution,as calculated from the DTS software using a Cumulants analysis of the measured intensity autocorrelation function;it is related to the standard deviation of the hypothetical Gaussian distribution(i.e.,PDI¼s2/Z2D, where s is the standard deviation and Z D is the Z average mean size).Transmission Electron Microscopy(TEM)The sizes and morphologies of the star polymers were ob-served using a transmission electron microscopy JEOL1400 TEM at an accelerating voltage of100kV.The star polymer were dispersed in water(5mg/mL)or in THF(5mg/mL) according the solubility of the material and deposited onto 200mesh,holey film,copper grid(ProSciTech).Osmium vapor(OsO4)staining was applied.SynthesesSynthesis of RAFT AgentsThe synthesis3-(benzylsulfanylthiocarbonylsulfanyl)-propi-onic acid(BSPA,1-Scheme1)has been described earlier.581H NMR(300.17MHz,CDCl3,298K):d/ppm¼2.85(2H,t, J¼6.8Hz,C H2C(O)OH),3.62(2H,t,C H2CH2),4.61(2H,s, C H2-Ph),7.31(5H,m,CH(C6H5).13C NMR(75.48MHz,CDCl3,298K):d/ppm¼224.1,179.2, 136.2,130.7,130.1,129.2,42.9,34.4,32.3.Synthesis of Pentafluorophenyl Acrylate(PF-A)6.2g of pentafluorophenol(33.8mmol),3.5g of triethyl-amine(35.0mmol),and30mL of dichloromethane were introduced into round bottom flask.The solution was placed in ice bath,and3.0mL of acryloyl chloride(36.8mmol)was slowly added.The solution was stirred for4h at room tem-perature.The triethylammonium chloride salt issue of the esterification reaction was removed by filtration,and the solid was washed with10mL of DCM.The solution was extract twice with10mL of acidic water(pH¼2.0),and af-ter twice with10mL of basic solution(Na2CO3),and finally, twice with10mL of distilled water.The organic phase was dried over anhydrous sodium sulfate(Na2SO4),and then, DCM was removed using a rotary evaporator to yield a yel-low liquid.This liquid was distilled under reduced pressure to give a colorless liquid(yield:60%).Note:100mg of6-di-Butyl-4-methylphenol(BHT)was added before the distilla-tion to avoid the polymerization.1H NMR(300.17MHz,CDCl3,298K):d/ppm¼6.70(C H2, 1H,d),6.36(C H2,1H,dd)and6.16(C H,1H,dd).19F NMR(282.41MHz,CDCl3,298K):d/ppm¼À163.6(2F, dd),À158.4(1F,t),À153.5(2F,d).13C NMR(75.48MHz,CDCl3,298K):d/ppm¼125.5,127.9, 133.5,133.7,134.2,140.0,165.2.Synthesis of Poly(pentafluorophenyl acrylate)Arm HomopolymerThree different molecular weights were targeted,and a sum-mary of the reagents used are given in Table 1.Briefly,SCHEME1Synthesis of star polymer using arm first approach. TABLE1Summary of the Poly(PF-A)Polymers Used in This StudyPoly(PF-A)Arm a FP-Aa M n,theo(g/mol)bM n,NMR(g/mol)cM n,GPC(g/mol)d PDI df RAFT(%)ePoly(PF-A)-1755,0004,8005,500 1.1595 Poly(PF-A)-27010,0009,50010,500 1.1695 Poly(PF-A)-37515,00013,50014,500 1.1795a PF-A conversion calculated by19F NMR analysis and using the following equation:a FP-A¼[$IÀ158.0ppm/ ($IÀ158.0ppmþ$IÀ152.5ppm)]Â100,with$IÀ158.0ppm and$IÀ152.5ppm corresponding to integral of the signal at À158.0and atÀ152.5ppm,respectively.b Theoretical molecular weight calculated by the following equation:Mn,theo.¼a FP-AÂ([M]0/[RAFT]0)ÂMW MonomerþMW RAFT,with[M]0,[RAFT]0,MW Monomer and MW RAFT corresponding to monomer and RAFT concentration,molar mass of monomer and RAFT agent,respectively.c Experimental molecular weight calculated by1H NMR using the following equation:Mn,NMR¼[(5ÂI1.5–2.5ppm)/(3ÂI7.2ppm)]ÂMW MonomerþMW RAFT,with I1.5–2.5ppm and I7.2ppm corresponding to inte-gral of signal from1.5to2.5ppm and at7.2ppm,respectively.d molecular weight and PDI determined by GPC.e f RAFT RAFT functionality determined by UV-visible using the following equation:RAFT end-group Func-tionality¼(Abs305/e305)/[Polymer]0),where Abs305,e305,and[Polymer]0correspond to absorbance,extinc-tion coefficient at305nm(e305¼15,700/mol/cm58)and polymer concentration,respectively.pentafluorophenyl acrylate(PF-A),AIBN,3-benzylsulfanylth-iocarbonylsulfanyl-propionic acid and acetonitrile were placed into a50mL round bottom flask,equipped witha magnetic stirrer bar.The reaction mixture,maintained at0 C,was degassed by purging with nitrogen for20mins. The degassed solution was stirred at70 C for6h.At the end of the polymerization,the solution was placed in an ice bath and an aliquot was sampled for GPC and1H NMR analy-ses.The remainder of the reaction mixture was purified;ace-tonitrile was partially removed using a rotary evaporator under vacuum,and the concentrated solution was precipi-tated in methanol.Synthesis of Star Polymers via an Arm First Methodology A general procedure is provided.Poly(FP-A)arm polymers (200mg)were introduced into a vial equipped with a mag-netic stirrer,with AIBN(2mg)and toluene(2mL).Different amounts of cross-linker(N,N0-bis(acryloyl)cystamine(C1), N,N-methylene bisacrylamide(C2)or1,6-hexanediol diacry-late(C3))were added,and the vials were sealed and purged under nitrogen at0 C,for20mins.The reaction vials were placed in an oil bath at70 C for24h.At the end of the polymerizations,an aliquot was taken and analyzed by GPC and by NMR to determine the arm incorporation and the monomer and cross-linker conversions,respectively.The rest of the solution was purified by dialysis using membrane cutoff MW3500Da against acetone,dried under vacuum at40 C for48h,and then,sampled for1H NMR and GPC analyses. Similar experiments were conducted using acetonitrile as solvent.However,a broader PDI was obtained(PDI>1.5) and a low arm incorporation for all three cross-linker was measured,see Table2.The arm incorporation was calculated using the following equation:a Arm(%)¼[Intensity Arm/(Intensity ArmþIntensi-ty Star)]Â100,with Intensity Arm and Intensity Star correspond-ing to intensity of signals of arm and of star measured by GPC analysis using refractive index as a detector.Postmodification of Star Using Amino CompoundsA general procedure is provided.Poly(FP-A)star polymers, with M n,arm¼5000g/mol,(200mg,8.40Â10À4mol)were introduced into a vial equipped with a magnetic stirrer.Tet-rahydrofuran(THF,5mL)and triethylamine(200l L)were added to the flask.Amino compounds,for example,benzyl amine(100mg,9.2Â10À4mol,1.1equivalents(eq.))were dissolved in1mL of THF,and were added dropwise into the star solution.The solution was stirred overnight(14h)at room temperature.The crude solution was analyzed by19F NMR to determine the pentafluorophenyl ester conversion. The star polymers were purified by dialysis against ethanol, and dried before to be analyzed by1H NMR,19F NMR,and GPC analyses.The similar process was carried out for the different amino compounds,expect for gluosamine hydrochloride(300mg, 1.4Â10À4mol,1.6eq.)and galactose amine hydrochloride (300mg,1.4Â10À4mol,1.6eq.).Both compounds were dissolved in water(1mL).Poly(FP-A)star polymers,with M n,arm¼5500g/mol,(200mg,8.40Â10À4mol)were introduced into a vial equipped with a magnetic stirrer;tet-rahydrofuran(THF,3mL),dimethylformamide(DMF,2mL) and triethylamine(TEA,400l L)were added.Carbohydrate solution was added slowly to the star solution to avoid the precipitation of the polymers.The star polymers were puri-fied by dialysis against water with MWCO¼3500Da. Finally,the star polymers were analyzed by1H&19F NMR, FTIR,and dynamic light scattering(DLS)analyses.The FP conversion for the nucleophilic substitution was determined by19F NMR of reactional mixture and using the following equation:FP conversion¼[$À165.2ppm/ ($IÀ165.2ppmþ$À152.5ppm)]Â100.Simultaneous Postmodification of Star UsingAmino Compounds and Thiol-ene ReactionA general procedure is provided.Poly(FP-A)star polymers, with M n,arm¼5500g/mol,(200mg,8.40Â10À4mol of FP-A)were introduced into a vial equipped with a magnetic stirrer.Tetrahydrofuran(THF,5mL)and triethylamine(TEA, 200l L)were added to the flask.Amino compounds,for example,benzyl amine(100mg,9.2Â10À4mol,1.1equiva-lents(eq.))and fluorescein acrylate(20mg,5.0Â10À5mol, 1.25eq.)or DyLight633(provided by Thermo Scientific,0.1 mg,1.0Â10À7mol)were dissolved in1mL of DMF,and were added dropwise into the star solution.The solution was stirred overnight(14h)at room temperature.The crudeTABLE2Summary of the Poly(FP-A)Star Synthesized via RAFT Polymerization Using Different Cross-Linkers in AcetonitrileStars Cross-linker a Ratio b ArmM n(g/mol)ca monomer(%)da cross-linker(%)dArmincorporation(%)eStar M n(g/mol)fStar PDIby GPC fS1C185,50095945648,000 2.05 S2C285,50099986245,000 2.12 S3C385,50098965852,000 2.28a Nature of cross-linker used in this study,that is,C1–C3correspond to N,N0-bis(acryloyl)cistamine,N,N0-methylene bisacrylamide,and1,6-hex-anediol diacrylate(see Scheme1for the structures).b Optimal ratio of[Cross-linker]/[RAFT agent]for the maximum incorpo-ration for the arm polymers in the star structure.c Arm molecular weight determined by GPC.d Monomer and cross-linker conversion determined by NMR(see experimental part).e Weight arm incorporation in the star structure assessed by GPC deconvolution of the arm and star peak using the following equation Arm Incorp.¼I arm/(I armþI Star)Â100.f Molecular weight and PDI determined by GPC.solution was analyzed by19F NMR to determine the penta-fluorophenyl ester conversion.The star polymers were puri-fied by dialysis(MWCO¼12,000–14,000Da)against etha-nol for3days,and dried before to be analyzed by1H NMR, 19F NMR,and GPC analysis.The solution of the star poly-mers modified by fluorescein and DyLigh633maleimide appears yellow/orange and blue,respectively.RESULTS AND DISCUSSIONOptimization of the Star Synthesis via Arm FirstPoly(pentafluorophenyl-acrylate)(PFA)(1)arms were pre-pared via RAFT polymerization in the presence of3-(benzyl-sulfanylthiocarbonylsulfanyl)-propionic acid(BSPA)(2)as the RAFT agent and AIBN as the initiator at70 C in acetoni-trile.Three different polymer arms,with molecular weights from5000to15,000g molÀ1and PDIs< 1.20,were obtained(Table1).Experimental molecular weights assessed by both GPC and by NMR analyses were in good agreement with the theoretical values.After purification,the presence of RAFT end groups was confirmed by1H NMR spectroscopy and by UV-visible spectroscopy.The RAFT end-group func-tionality for these polymers was determined to be greater than95%by UV-visible spectroscopy(k¼305nm of C¼¼S bond),using the following equation:RAFT end-group Func-tionality¼(Abs305/e305)/[Polymer]0),where Abs305,e305,and[Polymer]0correspond to absorbance,extinction coeffi-cient at305nm(e305¼15,700/mol/cm)58and polymer con-centration,respectively.19F NMR spectroscopy confirms the presence of pentafluoro phenyl groups atÀ153,À157,and À162ppm.Subsequently,the linear polymers were chain extended in the presence of a cross-linker molecule,AIBN and a low concentration of monomer,with a[RAFT]:[AIBN]: [Monomer]:[Cross-linker]ratio¼1.0:0.3:10.0:X,with X¼4, 6,8,and16in toluene for6,24,and48h(Scheme1).After chain extension,the star polymers were analysed by GPC and by1H NMR spectroscopy to determine the arm incorpo-ration and the cross-linker monomer conversion.In this study,we used three different cross-linkers,two based on bis-acrylamide and one bis-acrylate.Both bis-acrylamide cross-linkers present a low solubility in toluene,while bis-ac-rylate is perfectly soluble.Effect of the Cross-Linker on the Star FormationTo investigate the effect of the cross-linker concentration and nature on the formation of poly(pentafluorophenyl acry-late)poly(FP-A)star,we worked at a fixed optimal reactant ratio,that has been determined and published previously, namely,a[RAFT]0:[Monomer]0:[Cross-linker]0ratio equal to1.0:10.0:8.0.The reaction was carried out in toluene as it was demonstrated in our earlier publication that this sol-vent allows a high incorporation of poly(oligoethylene glycol) (poly(OEG-A))and poly(tert-butyl acrylate)(poly(tert-BuA)) arm in the star structure.45b Finally,the lower molecular weight poly(PF-A)arm was initially tested in the presence of N,N0-bis(acryloyl)cistamine(C1),N,N0-methylene bisacryla-mide(C2)and1,6-hexanediol diacrylate(C3).Star formation was observed for all three cross-linkers.However,a high pol-ydispersity index of star prepared from C3was noted(>1.5)with only60%incorporation of arms,consistent with previ-ous published data using RAFT polymerization.45a In con-trast,when the core crosslinking was achieved with C1or C2,well-defined star polymers were obtained with a very narrow molecular weight distributions(typically,PDI<1.2) and an excellent incorporation of the arms in the star struc-tures[greater than85%,determined via deconvolution of the GPC traces,see Fig.1(A)].However,C1cross-linker allows a higher incorporation of arm in the star structure than C2cross-linker.These results show that our previous method reported for the synthesis of star using poly(OEG-A), poly(tert-Bu A)or poly(NIPAAm)arms can be extended to the poly(pentafluorophenyl acrylate)arm polymers.To con-firm that the nature of solvent plays a key role,the synthesis of star was carried out in acetonitrile as solvent using simi-lar experimental conditions(cross-linker,concentration,etc). In acetonitrile,all three cross-linkers are perfectly soluble. We obtained relatively broad distribution for all the three cross-linkers(PDI>1.5)with relatively low arm incorpora-tion(around60%),when acetonitrile is used as solvent,for an arm molecular weight equal to5500g/mol(Table2). These promising initial results using toluene as solvent and C1-C2as cross-linker motivated us to probe the experimen-tal conditions to find optimum conditions for the synthesis of star polymers using poly(PF-A)arm.First,different[RAFT]:[Cross-linker]ratios(from1:2to 1:16)were tested using the similar recipe detailed in the previous section.The incorporation of the arm into the star structure increased with the increase of cross-linker to reach an optimal concentration around1:6–1:8[Fig.1(B)].How-ever,for a ratio greater than1:16,the solution became tur-bid and we observe a loss of solubility of star.The optimal FIGURE1GPC traces of the unpurified star polymers obtained with arm M n¼10,500g/mol:(-)obtained using C1cross-linker, (-)with C2cross-linker,and(-)with C3cross-linker.Experimen-tal condition:[monomer]:[cross-linker]:[RAFT]¼10:10:1at70 C for24h.Note:peak centred at33min corresponds to the unreacted arm.[Cross-linker]:[RAFT]ratio was determined around8:1,and this ratio was then used in the following work.Effect of the[Monomer]:[Cross-linker]RatioThe[Monomer]:[Cross-linker]ratio was investigated from0 to 1.5using poly(PF-A)arm with a molecular weight of 10,500g/mol.The star obtained were analysed by GPC[Fig. 2(A)].The increase of the[Monomer]:[Cross-linker]ratio results by an increase of the molecular weight of star poly-mer[Fig.2(B)].It is noteworthy that the absence of mono-mer results in a low incorporation of arms into the star structures.Influence of the Molecular Weight of the Armin the Formation of Star PolymersThe optimal condition,that is,[Monomer]:[Cross-linker]: [RAFT]¼10:8:1,was tested for all the polymeric arms synthe-sized.Figure3shows the GPC traces for the star formation reactions for each of the different molecular weight arms.As the molecular weight of the arm increases there is a corre-sponding decrease in the efficiency of incorporation of thearms into the star structure.For M n,by GPC¼5500g/mol,we observed a near full incorporation of the arms into the starstructure(>90%).In addition,even though the efficiency ofincorporation of the arms decreased,as the molecular weightof the arms increased,the molecular weight of the star formedalso increased;from90,000to135,000g/mol.In conclusion,we have obtained optimal condition for the syn-thesis of poly(FP-A)star via RAFT polymerization with a nearincorporation of the arms into the star structures,see Table3.Postfunctionalization of the Star ArmsThe presence of activated ester(pentafluorophenyl ester) (FP)groups was exploited to attach a variety of amino com-pounds to yield functional stars.In this approach,benzyl amine,isopropylamine,hydroxylpropyl amine,galactose amine and glucose amine were used to postfunctionalize the stars in the presence of triethylamine(TEA).Typical,we used a slight excess of amino compounds(1.2eq./1.0eq.ofFIGURE2Evolution of the molecular weights of the star poly-mers versus[Monomer]:[Cross-linker]ratio using cross-linker 2.(A)GPC traces of the unpurified star polymers:(-)[Mono-mer]:[Cross-linker]ratio¼0,(-)[Monomer]:[cross-linker]ratio ¼0.5,(-)[Monomer]:[Cross-linker]ratio¼1.0,(-)[Monomer]: [cross-linker]ratio¼1.25,(-)[Monomer]:[Cross-linker]ratio¼2.0;(B)Evolution of molecular weight and PDI versus[Mono-mer]:[Cross-linker].FIGURE3Evolution the star molecular weight and PDI versusarm molecular weights using the optimal condition:[Mono-mer]:[Cross-linker(1)]:[RAFT]¼10:10:1at70 C for24h in tolu-ene:A-GPC traces of crude star polymers obtained withdifferent arm molecular weight;B-Evolution of the star molec-ular weight and PDI versus arm molecular weight.T A B L E 3S u m m a r y o f t h e O p t i m a l P o l y (F P -A )S t a r S y n t h e s i z e d v i a R A F T P o l y m e r i z a t i o n U s i n g D i f f e r e n t C r o s s -L i n k e r s i n T o l u e n eS t a r sC r o s s -l i n k e raR a t i obA r m M n(g /m o l )c a m o n o m e r (%)d a c r o s s -l i n k e r(%)dA r m i n c o r p o r a t i o n e(%)S t a r M n(g /m o l )f S t a r P D I b y G P C f S t a r S i z e (n m )g S t a r P D I b y D L SS t a r M n(g /m o l )hN u m b e r o f a r m iS 1C 185,50098969665,0001.15140.09110,00020S 2C 1810,50097969290,0001.18150.08160,00016S 3C 1814,500989688122,0001.16180.10220,00015S 4C 285,50098978862,0001.19110.1295,00017S 5C 2810,50099978070,0001.18130.11140,00014S 6C 2814,500989675118,0001.14180.12190,00013S 10C 385,50095966042,2002.28130.21n dn dS 11C 3810,50095964045,0002.14160.15n dn dS 12C 3814,50095963052,0002.65220.17n dn daN a t u r e o f c r o s s -l i n k e r u s e d i n t h i s s t u d y ,t h a t i s ,C 1-C 3c o r r e s p o n d t o N ,N 0-b i s (a c r y l o y l )c i s t a m i n e ,N ,N 0-m e t h y l e n e b i s a c r y l a m i d e ,a n d 1,6-h e x a n e d i o l d i a c r y l a t e (s e e S c h e m e 1f o r t h e s t r u c t u r e s ).bO p t i m a l r a t i o o f [C r o s s -l i n k e r ]/[R A F T a g e n t ]f o r t h e m a x i m u m i n c o r p o r a t i o n f o r t h e a r m p o l y m e r s i n t h e s t a r s t r u c t u r e c A r m m o l e c u l a r w e i g h t d e t e r m i n e d b y G P C d M o n o m e r a n d c r o s s -l i n k e r c o n v e r s i o n d e t e r m i n e d b y N M R (s e e e x p e r i m e n t a l p a r t )e W e i g h t a r m i n c o r p o r a t i o n i n t h e s t a r s t r u c t u r e a s s e s s e d b y G P C d e c o n v o l u t i o n o f t h e a r m a n d s t a r p e a k u s i n g t h e f o l l o w i n g e q u a t i o n A r m I n c o r p .¼I a r m /(I a r m þI S t a r )Â100f A r m m o l e c u l a r w e i g h t a n d P D I o b t a i n e d b y D M A c G P C g D e t e r m i n e d b y d y n a m i c l i g h t s c a t t e r i n g i n T H F a t 1m g /m L (D L S )h M o l e c u l a r w e i g h t c a l c u l a t e d b y D L S i N u m b e r o f a r m s c a l c u l a t e d u s i n g t h e f o l l o w i n g e q u a t i o n :N a r m ¼S t a r M D L S n /M A r m n,n d :n o t d e t e r m i n e d .。