基于L-亮氨酸手性两亲性共聚物的制备及手性识别性能研究
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摘要
以L-亮氨酸(L-leu)为手性源,经酯化、酰胺化步骤制备手性单体N-甲基丙烯酰基-L-亮氨酰甲胺(MALMA),通过普通自由基聚合与聚乙二醇单甲醚1 000大分子单体(MPEGAA)共聚,制备一系列两亲性共聚物P(MALMA-co-MPEGAA)。利用核磁共振谱(1 H NMR)、红外光谱(FT-IR)、凝胶渗透色谱(GPC)、透射电镜(TEM)、紫外吸收及旋光仪等对聚合物的结构与形态进行表征。结果表明,制备的无规两亲性共聚物分子量分布较宽,可以在水中形成球形胶束粒子,包覆药物后粒径由包覆前的50~60nm增大到了70~75nm;胶束粒子对BOC-L-和BOC-D-苯丙氨酸具有选择性释放,具有手性识别的性能,并且随着手性基团的增多识别作用会增加,并通过核磁1 H NMR对产生手性识别的作用力进行了确认。
A series of amphiphilic copolymers P(MALMA-co-MPEAA)were synthesized by common free radical polymerization using macromonomer monomethyl polyethylene glycol1 000 ether acrylate(MPEGAA)and chiral monomer N-methacryloyl-L-leucylmethylamine(MALMA),which was prepared via esterification and amidation reaction from chiral source L-Leucine(L-leu).The structure and morphology of copolymer were characterized by nuclear magnetic resonance(1 H NMR),infrared spectroscopy(FT-IR),gel permeation(GPC),transmission electron microscope(TEM),UV ray absorption and polarimeter.The results showed that the molecular weight distribution of the random amphiphilic copolymer is broad and it can form spherical micelles in the water.After drug is loaded,the particle sizes increase from 50-60 to 70-75 nm.BOC-L and BOC-D-phenylalanine can be selectively released from micelle particles,indicating that micelles have chiral recognition properties,and the ability of chiral recognition increases with the increasing amount of chiral groups.The 1 H NMR characterization was used to confirm the results.
A series of amphiphilic copolymers P(MALMA-co-MPEAA)were synthesized by common free radical polymerization using macromonomer monomethyl polyethylene glycol1 000 ether acrylate(MPEGAA)and chiral monomer N-methacryloyl-L-leucylmethylamine(MALMA),which was prepared via esterification and amidation reaction from chiral source L-Leucine(L-leu).The structure and morphology of copolymer were characterized by nuclear magnetic resonance(1 H NMR),infrared spectroscopy(FT-IR),gel permeation(GPC),transmission electron microscope(TEM),UV ray absorption and polarimeter.The results showed that the molecular weight distribution of the random amphiphilic copolymer is broad and it can form spherical micelles in the water.After drug is loaded,the particle sizes increase from 50-60 to 70-75 nm.BOC-L and BOC-D-phenylalanine can be selectively released from micelle particles,indicating that micelles have chiral recognition properties,and the ability of chiral recognition increases with the increasing amount of chiral groups.The 1 H NMR characterization was used to confirm the results.
引文
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[2]Stefan R I,Staden J F V,Aboul-Enein H Y.Molecular recognition in chiral discrimination[J].Crystal Engineering,2001,4(2-3):113-118.
[3]Tang J,Pang L,Zhou J,et al.Per(3-chloro-4-methyl)phenylcarbamate cyclodextrin clicked stationary phase for chiral separation in multiple modes high-performance liquid chromatography[J].Analytica Chimica Acta,2016,946:96.
[4]Ku cˇerovG,ProchzkovH,KalíkovK,et al.Sulfobutylether-β-cyclodextrin as a chiral selector for separation of amino acids and dipeptides in chromatography[J].Journal of Chromatography A,2016,1467:356-362.
[5]Chen H,Cheng H,Lee J,et al.Surface plasmon resonance spectroscopic chiral discrimination using self-assembled leucine derivative monolayer[J].Talanta,2008,76(1):49-53.
[6]Zhang Y X,Zhao P Y,Yu L P.Highly-sensitive and selective colorimetric sensor for amino acids chiral recognition based on molecularly imprinted photonic polymers[J].Sensors&Actuators B Chemical,2013,181(5):850-857.
[7]Zhou Q,He J,Tang Y,et al.A novel hydroquinidine imprinted microsphere using a chirality-matching N-Acryloyl-L-phenylalanine monomer for recognition of cinchona alkaloids[J].Journal of Chromatography A,2012,1238(10):60.
[8]Li M,Lin X,Xie Z.Investigation of enantiomer recognition of molecularly imprinted polymeric monoliths in pressurized capillary electrochromatography screening the amino acids and their derivatives[J].Journal of Chromatography A,2009,1216(27):5320-5326.
[9]Dressler D H,Mastai Y.Enantioselective crystallization of histidine on chiral self-assembled films of cysteine[J].Journal of Colloid&Interface Science,2007,310(2):653-660.
[10]Ingole P G,Bajaj H C,Singh K.Preparation of enantioselective membranes for optical resolution of chiral compounds[J].Procedia Engineering,2012,44:358-360.
[11]Scriba G K.Chiral recognition in separation science-an update[J].Journal of Chromatography A,2016,1467:56-78.
[12]Wang Xiaodong,Yao Jinshui,Wei Mingxin,et al.Study on chiral recognition and amino acid chiral stationary phase[J].Chinese Journal of Organic Chemistry,2006,26(7):912-921(in Chinese).王晓东,姚金水,魏明星,等.手性识别及氨基酸类手性固定相的研究进展[J].有机化学,2006,26(7):912-921.
[13]Nakayama D,Nishio A Y,Watanabe M.Inter/intramolecular interaction and chiral recognition of water-soluble copolymers and their hydrogels containing an optically active group[J].Langmuir,2003,19(20):8546-8549.
[14]Zhang Chunhong,Wang Hailun,Liu Fangbing,et al.Study on chiral recognition of spiral polyphenylene vinyl acetylene derivatives with L-amino acetate in side chains[J].Acta Polymerica Sinica,2013(6):000811-816(in Chinese).张春红,王海伦,刘方彬,等.侧链带有L-氨基酸乙酯的螺旋聚苯乙炔衍生物的手性识别能力研究[J].高分子学报,2013(6):811-816.
[15]Bai Jianwei,Shen Xiande,Liu Wenbing,et al.Synthesis and chiral recognition of optically active methacrylamide polymers with phenylglycine as side chains[J].Acta Polymerica Sinica,2013(4):419-425(in Chinese).白建伟,沈贤德,刘文彬,等.以苯甘氨酸基为侧链的光学活性甲基丙烯酰胺聚合物的合成及手性识别能力[J].高分子学报,2013(4):419-425.
[16]Wang J,Warner I M.Chiral separations using micellar electrokinetic capillary chromatography and a polymerized chiral micelle[J].Analytical Chemistry,1994,66(21):3773-3776.
[17]Liu Zhan,Wang Weiru,Gao Yanfang,et al.Synthesis of water-soluble comb polymer containing mPEG side chains and its side chain limited crystallization behavior[J].Acta Polymerica Sinica,2006,1(1):26-31(in Chinese).刘崭,王蔚茹,高彦芳,等.含mPEG侧链的水溶性梳状聚合物的合成及其侧链受限结晶行为研究[J].高分子学报,2006,1(1):26-31.
[18]Cavazzini A,Nadalini G,Dondi F,et al.Study of mechanisms of chiral discrimination of amino acids and their derivatives on a teicoplanin-based chiral stationary phase[J].Journal of Chromatography A,2004,1031(1-2):143.
[19]Machida Y,Nishi H,Nakamura K.Nuclear magnetic resonance studies for the chiral recognition of the novel chiral stationary phase derived from 18-crown-6tetracarboxylic acid[J].Journal of Chromatography A,1998,810(1-2):33-41.
[20]Machida Y,Kagawa M,Nishi H.Nuclear magnetic resonance studies for the chiral recognition of(+)-(R)-18-crown-6-tetracarboxylic acid to amino compounds[J].Journal of Pharmaceutical&Biomedical Analysis,2003,30(6):1929-1942.
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