基于聚氨基酸的线型-树状聚两性电解质的合成及pH响应性研究

SYNTHESIS AND pH REVERSIBLE AGGREGATING BEHAVIOR OF POLY(AMINO ACID) BASED LINEAR-DENDRON-LIKE POLYAMPHOLYTE

采用开环聚合、发散法以及"点击化学法"合成了线型-树状聚两性电解质.首先通过γ-苄基-L-谷氨酸酯羧酸酐(BLG-NCA)的开环聚合及发散合成法分别合成了叠氮端基聚(γ-苄基-L-谷氨酸酯)(PBLG-N3)及以炔基为内核的带有4个伯氨端基的第2.0代聚酰胺-胺(PAMAM-D2),再将二者通过"点击反应"制备的线型-树状嵌段共聚物PBLG-b-D2作为大分子引发剂,利用其末端氨基引发ε-苄氧羰基-L-赖氨酸羧酸酐(ZLL-NCA)的开环聚合,获得线型-树状嵌段共聚物PBLG-b-D2-(PZLL)4,再经酸解脱除PBLG上的苄基及PZLL上的苄氧羰基,获得目标产物聚(L-谷氨酸)-b-聚[酰胺-胺-聚(L-赖氨酸)](PLGA50-b-D2-(PLL9)4)线型-树状聚两性电解质.通过核磁(1H-NMR)、傅里叶变换红外光谱(FTIR)和凝胶渗透色谱(GPC)表征了聚合物分子结构、分子量及其分布;通过电导滴定法、1H-NMR、zeta电位、激光光散射(LLS)、扫描电子显微镜(SEM)及圆二色谱(CD)等方法研究了PLGA50-b-D2-(PLL9)4对溶液pH值响应性.结果表明随溶液pH由酸性转变为碱性,PLGA50-b-D2-(PLL9)4显示出了多重胶束化行为,同时不对称的线型-树状分子拓扑结构影响了聚集体的形貌,在酸性pH值下形成以PLGA为核的球形胶束,而在碱性pH值下形成以PLL为核的棒状胶束,并分别伴随着PLGA及PLL链段构象从无规线团向螺旋构象的转变.

A linear-dendron-like polyampholyte was synthesized via the combination of ring-opening polymerization （ROP）, divergent synthesis procedure and click chemistry. First, azide-terminated poly （y- benzyl-L-glutamate） （PBLG-N3） and the second generation PAMAM （D2） with alkyne focal group and four terminal primary amine groups were synthesized by the ROP of y-benzyl-L-glutamate N-carboxyanhydride （BLG-NCA） and divergent synthesis procedure, respectively. Subsequently, PBLG-N3was click conjugated with alkyne focal group of D2 to generate primary amine-terminated linear-dendron-like PBLG-b-D2,which was then used as the microinitiator for the ROP of 8-benzyloxycarbonyl-L-lysine N-carboxyanhydride （ZLL-NCA） to produce the linear-dendron-like copolymer PBLG-b-D2-（ PZLL ）4- The targeted linear-dendron-like polyampholyte, PLGAs0-b-D2- （ PLL9 ） 4, where PLGA is poly （ L-glutamic acid） and PLL is poly （ L-lysine）, was obtained by the hydrolysis of protecting benzyl and benzyloxycarbonyl groups of PBLG and PZLL,respectively. The molecular structures of the intermediates and the final polyampholyte were characterized by 1H-NMR, Fourier transform-infrared spectroscopy （FTIR） and properties and pH-responsive behavior in aqueous gel permeation chromatograph （GPC）. The physical solution were investigated via potentiometric and conductometric titration, 1H-NMR, zeta potential measurement, laser light scattering （ LLS）, scanning electron microscopy （SEM） and circular dichroism spectroscopy （CD）. The results show that PLGA50-b-D2-（ PLL9 ）4 can self-assemble into schizophrenic micelles which can be reversibly produced as a function of pH in pure water,i, e. , it can self-assemble into spherical micelles with PLGA-core at acidic pH and rod-like micelles with PLL-core at alkaline pH, accompanied with the coil-to-helix conformational transition of PLGA and PLL. The linear-dendron-like asymmetrical topological structure is believed to play an impotent role in the morphology formation of self-assembly nanostructures.