悬浮聚合法制备手性螺旋聚炔微球及其对映体选择性释放性能研究

This project is intended to prepare optically active helical polymer microspheres based on substituted acetylene monomers via suspension polymerization approach. Moreover, according to a novel strategy which judiciously combines two quite distinct concepts of optical resolution and drug delivery in one entity, the resulting microspheres will be explored in terms of enantioselective release property. In view of the fact that suspension polymerizations have been successfully realized in vinyl monomers and are currently extensively investigated, by which a great number of vinyl polymer-based microspheres have been prepared, the present project is especially highlighted in creating techniques for performing suspension polymerizations of acetylenics. Such processes will lead to interesting optically active microspheres fabricated from helical polyacetylenes. Apart from optically active microspheres, more other intriguing microspheres with various morphology and other attractive functions will also be constructed (e.g. porous, molecular-imprinted microspheres). All the as-obtained microspheres will be investigated in terms of enantioselective release, aiming at developing novel materials toward this target. Some unique properties are anticipated from the unprecedented optically active microspheres, in particular the characteristics of helical macromolecular structures and the corresponding chirality at micro-scales. The helical structures of the polymer chains may exert essential effects on the optical activity of the microspheres. Synergic effects may be hopefully observed in the helical polymers upon forming microspheres. Additionally, the unique helical architectures probably play large influence on the fabrication of polymer microspheres and even their morphology. The project will also provide new insights into chiral helical polymers, in particular their chiral interactions with enantiospecific compounds, and the potentials as novel auxiliary agents for controlled release of chiral compounds.

本项目针对手性螺旋聚合物和控制释放等极具挑战性的基础科学问题，旨在建立手性螺旋聚炔微球制备新方法，开拓手性聚合物新应用，发展手性物质控释新技术。悬浮聚合制备烯类聚合物微球已大规模工业化；但炔类单体悬浮聚合还是一项学术空白。本项目(1)将建立炔单体进行(反相)悬浮聚合的方法，制备手性螺旋聚炔微球，并进一步丰富其种类(手性多孔、分子印迹微球等)；(2)揭示微球光学活性与聚合物螺旋结构间的内在联系及基本规律、微米尺度上螺旋结构及手性特征、螺旋分子链间的协同效应、螺旋结构对成球及微球形貌影响等科学规律；(3)将手性拆分和控制释放相结合，系统研究微球的对映体选择性释放性能。该项目除可获得多种新型手性聚合物微球及建立其行之有效的制备方法外，还将揭示聚合物螺旋结构在手性物质控制释放过程中的作用，探索所涉及到的手性识别、手性缓/控释等基础问题；尤其是手性拆分和控制释放耦合，有望建立手性物质控制释放新体系。

活性物质控制释放是一个多学科交叉性前沿研究领域，受到了不同学科专家的高度重视；另一方面, 手性物质、手性科学和手性技术的重要性正在日益凸显。目前手性化合物的制备主要是不对称催化和手性拆分, 但具有耗时、成本高等不足；因而有必要开辟手性药物、农药等的使用新策略和新途径。基于此研究背景，该项目围绕手性螺旋聚合物新材料的设计、制备和应用，提出和发展对映体选择性控制释放策略，以期将“手性拆分”和“药物控释”两个相互独立的过程结合于一体，旨在建立手性物质使用新途径。该项目在下列几个方面取得了进展：（1）建立和发展了单取代炔单体悬浮聚合等新方法，弥补了乳液聚合和沉淀聚合不能制备较大粒径手性聚合物粒子的缺陷；（2）制备了系列由螺旋聚合物所构筑的手性新材料（核壳粒子、磁性粒子、杂化粒子、多孔粒子、Monolith等）；（3）手性聚合物粒子等手性材料作为新型物质释放载体，呈现较好的对映体识别性能和药物控制释放性能；（4）释放研究表明：当手性基体含有2种以上手性因素时（手性螺旋聚合物＋手性分子印迹；两种不同的手性螺旋聚合物），不同手性因素间具有协同效应，能显著提高载体的对映体选择性能；（5）围绕研究主题，开展了一些拓展性研究（基于生物质和聚乳酸开发手性新材料），不仅建立了一系列聚合新技术，极大地丰富了手性材料的种类，同时还引入“绿色化学”理念，为手性聚合物的可持续发展提供了新思路，为进一步开发手性聚合物材料的应用价值（不对称催化、手性拆分、手性识别、手性光学材料等）提供了科学基础。至结题时共发表SCI论文50篇，包括Macromolecules（6篇）、ACS Macro Lett. (3篇)、Macromol. Rapid Commun.（5篇）、Polym. Chem. (4篇)、ACS Appl. Mater. Interfaces (3篇)等国际知名刊物；为Polym. Rev., Ind. Chem. Eng. Res., Chem. Rec. 等撰写综述论文。共培养研究生18人（博士毕业生4人，在读2人；硕士毕业生6人，在读6人）。该项目为手性螺旋聚合物微纳材料构筑以及手性应用研究做出了贡献，也为后续研究打下了坚实的科学基础。