Enzymatic Synthesis and Characterization of Novel Amphiphilic Triblock Copolymer Poly(p-dioxanone-co

Chinese Chemical Letters Vol. 17, No.8, pp 1113-1116, 20061113http://www.imm.ac .cn/journal/ccl.htmlEnzymatic Synthesis and Characterization of NovelAmphiphilic Triblock Copolymer Poly(p-dioxanone-co-5- benzyloxytrimethylene carbonate)-block-poly(ethylene glycol)Hua Li JIA, Feng HE*, Jun FENG, Ren Xi ZHUOKey Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry,Wuhan University, Wuhan 430072Abstract: Novel amphiphilic triblock copolymer poly(p-dioxanone-co-5-benzyloxytrimethylenecarbonate)-block-poly(ethylene glycol)-block-poly(p-dioxanone-co -5-benzyloxytrimethylene car-bonate) (p(PDO-co- BTMC)-b-PEG-b-p(PDO-co-BTMC)) was successfully synthesized usingimmobilized porcine pancreas lipase on porous silica particles (IPPL) as the catalyst for the firsttime. 'H NMR, C NMR and GPC analysis were used to confirm the structures of resultingcopolymers. The molecular weight (M.) of the copolymer with feed ratio of 69:20:11 (BTMC:PDO: PEG ) was 31300 g/mol and the polydispersity was 1.85, while the M。decreased to 25000g/mol and polydispersity of 1.93 with the feed ratio of 50:40:10.Key words: Amphiphilic copolymer, poly(ethylene glycol), 5-benzyloxytrimethylene carbonate,p-dioxanone, enzymatic polymerization.In recent years, amphiphilic block copolymers consisting of hydrophilic and hydrophobicsegments have attracted much attention, because of their unique phase behavior inaqueous media and potential applications as drug delivery systems'. Poly(ethyleneglycol) (PEG), which have excellent properties including hydrophilicity, water solubility,biocompatibility and notoxicity, has been widely used as hydrophilic segments toconstruct amphiphilic copolymers'.'Aliphatic polycarbonates have been proved to be a kind of material with goodbiocompatibility and low toxicity'. However, the poor hydrophilicity and slowdegradation rates of aliphatic polycarbonates limit their wide application, which can beimproved by introduction of functional pendent groups, as well as copolymerization withother hydrophilic monomers'.7. Poly(p-dioxanone) (PPDO) is a semi-crystalline poly-ester with outstanding biocompatibility, biodegradability and flexibility". However, thehydrophilicity of copolymers containing PPDO and aliphatic polycarbonate wasimproved with a certain extent because of the lower monomer conversion of the PDO*.9.Enzymatic polymerization has generated an中国煤化工.rch as a newenvironmentally friendly method of polymer synd high cost:TYHCNMHGE-mail: fenghe2002 @hotmail.com1114Hua Li JIAet al.are the disadvantages existing in the application of enzyme catalysts, while the enzymeimmobilization is an effective method to resolve the problems. In our previous study,immobilized porcine pancreas lipase on porous silica particles (IPPL) was successfullyemployed as the catalyst to synthesize different kinds of polyesters and polycarbonates'In this paper, a novel amphiphilic triblock copolymer with PEG as hydrophilicsegments was firstly synthesized in the presence of IPPL catalyst. The randomcopolymer poly(p-dioxanone co-5-benzyloxytrimethylene carbonate) (p(PDO-co- BTMC)was used as hydrophobic segments, while the protecting benzyl groups of BTMC can beremoved by catalytic hydrogenation to give the pendant hydroxyl groups which facilitatefurther modification'. It also expected to synthesize this novel functional triblockcopolymer with different contents and properties for different applications.ExperimentalBTMC and PDO were synthesized according to the literatureb, .IPPL was preparedaccording to He'. Dihydroxyl PEG (Mw=6000) was purchased from ShanghaiChemical Reagent Company, and dried in vacuo before use.The copolymerization was carried out in bulk at 150°C. A mixture of BTMC,PDO, PEG (total amount of 0.5 g) was introduced to a dried glass flask with a magneticstirrer.After a certain amount of IPPL (4.5 wt%o of monomers) catalyst was added, theflask sealed under vacuum, and then put in an oil bath at 150°C for 24 hours. Theobtained product was dissolved in dichloromethane. The insoluble IPPL was filteredoff, and the crude copolymer was further precipitated in excess methanol. The final .product was dried in vacuum at room temperature to constant weight.Results and DiscussionTriblock copolymers (p(PDO-co- BTMC)-b-PEG-b-p(PDO-co-BTMC)) were synthesizedby enzymatic ring-opening copolymerization using PEG as macroinitiators (shown inScheme 1). The structures of the resulting polymer were characterized by 'H NMR',"3C NMR 16 and GPC (data shown in ref 15 and 16).Compared with the spectrum of PBTMC and PPDO homopolymers, the resonanceof carboxyl groups in p(PDO-c0-BTMC) segments separated into several peaks, due tothe different chemical environments caused by the different sequences in the copolymerchain.GPC results showed that the resuling triblock copolymers had unimodal molecularweight distributions, and the polydispersities were of 1 .56 and 1 .59, respectively. Therewas no peak in the zone of low molecular weights, indicating the absence of residualPEG, PDO or BTMC. As showed in Table 1, when PEG contents keep constant, thePDO contents in feed ratio increased from 20 to 40 resulted in the decrease of the Mn ofthe copolymers from 31300 to 25000 g/mol, whil中国煤化工from 68% to61%. The reason may be the lower reactivityas consistentwith reference .TYHCNMHGAmphiphilic Triblock Copolymer Poly(p-dioxanone-co-5 -benzyloxy- 1115trimethylene carbonate)-block-poly(ethylene glycol)Scheme 1 Enzymatic synthesis of p(PDO-co-BTMC)-b- PEG-b- p(PDO-co-BTMC)IPPLR + HfoCH2CH+ot+n150°C Bulk6CH2PhOHCHCHCH.HCtHOCHCH20H.+CHCH2OHOHC.CCH中. fCH,OCH2CH2oH.'m-xOCH2PhbCH2Php(BTMC-co-PDO)PEGTable 1 Enzymatic synthesis and characterization of p(PDO-co-BTMC)-b-PEG-b-p(PDO-co- .BTMC)Sample aBTMC:PDO:PEG BTMC:PDO:PEG bM。°(M/M,)° Yield (%)(feed molar ratio)(product)50:40:1055:35:10250001.936269:20:1174:14:1231300I .8568a Reaction conditions: bulk copolymerization using IPPL (4.5 wt%o) as the catalyst at 150°Cfor 24 h.b Measured by 'H NMR.C Determined by GPC with THF as the eluent.The further investigations on the properties and applications of the copolymers withdifferent contents are under way in our laboratory.AcknowledgmentThe authors are grateful for the financial support of the National Natural Science Foundation ofChina (No. 20104005).References and Notes1. 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Doddi, C. C. Versfelt, U.S. Pat, 4052988 (1977).1116Hua Li JIAet al.15. 'H NMR (300MHz, CDCl3, δ ppm) for sample 1: 3.65 (PEG, O-CH2CH2.O), 3.83(BTMC,O-CH2-CH-CH2-O), 4.10-4.31 (BTMC, O-CH2-CH-CH2-O), 4.64(BTMC, O-CH2-Ph), 7.32(BTMC, O-CH2-Ph), 3.74-3.78(PDO, O-CH2-CH2O-CO), 4.17(PDO, O-CH2-CO), 4.2-4.3(PDO, O-CH2,CH2-O-CO).16.'C NMR(75MHz，CDCI], δ ppm) for sample 1: 70.78(PEG: 0-CH2.CH2O), 170.32,170.08(PDO: -CO-O), 155.10, 154.98(BTMC: O-CO-O)，137.76, 128.69, 128.06(BTMC:O-CH2-Ph), 74.22 (BTMC: 0-CH2-CH), 72.40(BTMC: O-CH-CH), 69.44, 69.36 (BTMC:O-CH2-CH)，68.47, 68.38, 68.27(PDO: 0-CH2-CH2-O-CO), 66.74, 66.66, 67.24(PDO:OCH2-C0-O), 63.85, 63.27(PDO: O-CH2-CH2.O-CO).Received 19 January, 2006中国煤化工MHCNMHG