接枝树形支化分子双亲性嵌段共聚肽的合成及性能研究

Synthesis of Amphiphilic Dendronized Block Copolypeptides and Their Properties

分别以叠氮丙胺和丙炔胺为引发剂,采用氨基酸环内酸酐开环聚合法(NCA-ROP),引发L-谷氨酸-γ-苄酯-N-羧基-环内酸酐和L-谷氨酸-γ-氯乙醇酯-N-羧基-环内酸酐聚合得到链端基为叠氮基的聚(L-谷氨酸-γ-苄酯)(PBLG)和链端基为炔基的聚(L-谷氨酸-γ-氯乙醇酯)(PCELG)均聚物.联合点击化学法(click chemistry)制备了一系列聚(L-谷氨酸-γ-苄酯)-b-聚(L-谷氨酸-γ-氯乙醇酯)(PBLG-b-PCELG),再通过对嵌段共聚物侧基氯进行化学修饰,将二代的甲基烷氧醚类亲水性树形枝化分子(G2)接枝到侧链上,形成一系列树形支化分子接枝聚肽双亲性嵌段共聚物,通过核磁(NMR)、红外光谱(IR)和凝胶渗透色谱(GPC)对其化学结构进行了表征,并采用紫外-可见光谱(UV-Vis)研究了聚合物结构及其溶液浓度对其温敏行为的影响规律.

A series of novel amphiphilic block copolypepides bearing the hydrophilic second-generation（G2） dendritic ether grafts denoted as PBLG-b-（PELG-g-G2） were designed and synthesized by a combination of ring-opening polymerization and click chemistry. First, azido-terminated poly（γ-benzyl-L-glutamate）s（PBLG） with different molecular weights were synthesized by ring-opening polymerization of γ-benzyl-L-glutamate-Ncarboxyanhydride（BLG-NCA） in DMF at room temperature using 3-azido-1-propanamine as initiator and alkyne-terminated poly（γ-2-chloroethyl-L-glutamate）（PCELG） was synthesized by ring-opening polymerization of γ-2-chloroethyl-L-glutamate-N-carboxyanhydride in DMF at room temperature using propargylamine as initiator. The block copolypeptides poly（γ-benzyl-L-glutamate）-block-poly（γ-2-chloroethyl-L-glutamate）（PBLGb-PCELG） bearing chloride side groups were synthesized by click chemistry with high efficiency from the azido-terminated PBLG and the alkyne-terminated PCELG in the presence of Cu Br and 1,1,4,7,7-pentamethyldiethylenetriamine（PMDETA） catalyst system. Then, PBLG-b-PCELG containing chloride side groups was subsequently reacted with excessive sodium azide in DMF to yield a block copolypeptide bearing azido side groups denoted as PBLG-b-（PNELG）. The hydrophilic second-generation（G2） dendritic ethers were finally grafted to the side chains of the block copolypeptides PBLG-b-（PNELG） by click chemistry in the presence of Cu Br/PMDETA catalyst system and the amphiphilic dendronized block copolypepides PBLG-b-（PELG-g-G2） were successfully synthesized. Their molecular structures were further characterized by1H-NMR, FTIR and GPC. The thermo-responsive behaviour of PBLG-b-（PELG-g-G2） in water were investigated using UV-Vis and the results showed that the values of the cloud point temperatures（Tcp） of PBLG-b-（PELG-gG2） became lower with the length increase of the hydrophobic PBLG chain segment. This was explained by the fact that the amphiphilic block copolypeptides PBLG-b-（PELG-g-G2） in water self-assembled into core-shell micelles with the hydrophobic PBLG as the core and the hydrophilic dendronized polypeptide segment as the shell. The degree of hysteresis, defined as the difference in the cloud points upon heating and cooling, in each system lowered with the decrease in amphiphilic block copolypepide concentrations for micelles. The synthesized PBLG-b-（PELG-g-G2） may be expected to have good application prospects in the biomedical field due to the excellent biocompatibility of their structural units.