掺杂剂介导的液晶分子印迹手性传递色谱固定相的构建及其研究

Molecular imprinting is a unique method of constructing chiral stationary phase (CSP) with predetermined selectivity, but the need of the chiral molecule as template is a great challenge to CSP design, especially in condition of too expensive template molecule or no commercial optical pure template available. In this project, based on the stratgy of chiral induction and transfer from ordered nematic phase to helical cholesteric liquid crystal polymer, a new approach to chiral stationary phase of molecularly imprinted polymers prepared with racemic drugs as template by doping chiral molecules into the resulting polymers was developed. MIP capillary coating with polyhedral oligomeric silsesquioxane as auxiliary monomer and 3- aminopropyltriethoxysilane modified methacrylic acid as functional monomer, nanoparticles prepared with doping of nano silver, and grafted monolith MIPs will be prepared. The polymerization and separation mechanism of the inorganic / organic hybrid MIPs will be studied by polymerization kinetics, mass transfer dynamics, nonlinear chromatographic dynamics, thermodynamics of chiral separation. The relationship of polymerization parameters on the structure and properties of the new MIP will be summarized. In addition, new method towards chiral stationary phase of MIPs will be developed for separating fluconazole, quinoline, ticagrelor and aprepitant is expected as a new synthesis method to develop the highly efficient MIP chiral stationary phase low cost.

分子印迹是一种构建具有预定选择性手性固定相的独特方法，但制备时需要手性模板对其设计带来了极大的挑战，因此在模板分子过于昂贵或无商品化光学纯模板时该法受到了极大限制。本课题基于手性诱导及传递的设想，利用液晶聚合物在手性分子的掺杂作用下由排列规整的向列相变为螺旋形胆甾相的特点，提出一种新的以外消旋分子做模板的分子印迹聚合物（MIP）手性固定相设计合成方法。拟制备多面体低聚硅倍半氧烷为辅助单体的液晶MIP涂层、3-氨丙基三乙氧基硅烷修饰的甲基丙烯酸为功能单体制备液晶MIP涂层、纳米银液晶MIP及液晶接枝MIP整体柱，从聚合动力学、传质动力学、非线性色谱动力学、手性分离热力学等方面研究MIP的聚合和分离机制，总结聚合参数对新型无机/有机杂化MIP结构及性能影响的规律，在此基础上，实现对手性药物艾氟康唑、贝达喹啉、替格瑞洛及阿瑞匹坦的分离，为发展高效低成本的手性固定相合成方法奠定基础。

本课题基于手性诱导及传递的设想，利用液晶聚合物在手性分子的掺杂作用下由排列规整的向列相变为螺旋形胆甾相的特点，提出一种新的分子印迹聚合物（MIP）设计合成方法，并为了克服现有分子印迹聚合物的选择性弱、亲和力低，以及结合位点的可及性差等问题，引入新型功能单体，开发了多种新型印迹材料，可以有效解决印迹材料固有问题。本课题总结了聚合参数对新型MIP结构及性能影响的规律；针对常规分子印迹固定相由于固定模板分子的记忆需要高比例交联剂的使用，导致印迹位点包埋、印迹位点利用率低的痼疾，提出了构建更加开放的网络结构增加印迹位点可接近性的新思路，首次构建了基于多面体低聚倍半硅氧烷为交联剂的新型印迹固定相，在不降低印迹效率的前提下有效改进了位点包埋，增加了对印迹分子的结合容量；首次提出了基于坎尼扎罗反应的印迹后修饰技术，该方法通过印迹位点内定点化学修饰的手段，可有效解决共价印迹去除模板困难所导致的结合腔数量减少，增加了印迹分子的有效结合位点，并且由于不完全水解而可能引起的模板渗漏等问题。该法有望用于修饰蛋白质组学中肽的特异性捕获，并成为强大的修饰肽的分析鉴定工具。