基于物理交联的液晶分子印迹色谱固定相设计、合成及手性药物分离研究

To solve the main problems of the slow mass transfer, the difficulty in elution and the low loading capacity of molecularly imprinted polymer (MIP), a new idea was suggested that the memory to template molecule is kept with other modes. MIP stationary phase in low crosslinking degree was prepared first with rigid liquid monomers to form additional physical crosslinking. Based on previous liquid crystal-based MIP coating in capillary, capillary coating with multi-templates imprinting, crosslinker-free imprinted coating containing templated monomer, nanoparticles prepared with multi-initiators in local polymerization, and grafted monolith MIPs will be made. Moreover, the combination of monomers containing liquid and crystal templated monomers will be used to prepare MIPs without crosslinker. The ability of chiral separation will be evaluated using the new MIPs. The mechanism of mass transfer for the templates in the MIPs will be investigated by analysis of plate height and dynamics of mass transfer. The heterogeneity and accessibility of imprinted sites will be studied by frontal chromatography, thermodynamic parameters of chiral separation and adsorptive models. The relationship between the structure and performance of liquid crystal MIPs and polymerization variables will be summarized. In addition, new method towards multi-template MIPs will be developed to separate hydroquinidine, flurbiprofen , cetirizine and nitrendipine. This work provides a new strategy to develop the highly selective and efficient MIP chiral stationary phase. Furthermore, it will contribute to a theoretical and practical foundation to the development in next generation of MIPs materials and the stationary phase of high performance.

为解决分子印迹聚合物（MIP）制备时所需高交联度带来的传质慢、模板洗脱难及吸附容量低等痼疾，提出构建以其它方式保持印迹位点构型的新思路，并利用刚性棒状液晶单体形成额外物理交联网络结构的策略，首次开展低交联液晶MIP色谱固定相的研究。本课题在已成功研制低交联液晶MIP毛细管涂层手性固定相的基础上，开展多模板印迹涂层研究，结合模板单体优势构建无交联液晶MIP涂层；以基于多重引发剂的局部聚合方式制备低交联液晶MIP纳米粒；设计低交联液晶MIP接枝整体柱；并考察这些新型MIP的手性拆分能力。从传质动力学及板高分析等方面研究模板分子的传质机制；以前沿色谱、手性分离热力学及吸附模型表征其印迹位点的可接近性及不均匀性；总结聚合参数对新型MIP结构及性能影响的规律；在此基础上，实现对手性药物氢化奎尼丁、氟比洛芬、西替利嗪及尼群地平的分离。为发展高效MIP手性固定相及新一代MIP材料奠定理论和实践基础。

为解决分子印迹聚合物（MIP）制备时所需高交联度带来的传质慢、模板洗脱难及吸附容量低等痼疾，提出构建以其它方式保持印迹位点构型的新思路，并利用刚性棒状液晶单体形成额外物理交联网络结构的策略，本研究首次开展低交联液晶MIP色谱固定相的研究，制备了一批新型MIP色谱柱，包括基于POSS的液晶MIP毛细管涂层柱，组合液晶物理交联与模板单体策略的无化学交联剂的MIP毛细管涂层柱，基于手性掺杂剂的液晶MIP毛细管手性涂层柱，基于大分子拥挤效应的液晶MIP接枝整体柱，详细研究了聚合过程中一些重要的参数，如POSS含量、模板和单体比例、液晶单体含量和功能单体的组成对印迹效果、柱效和分离性能的影响，还考察了色谱条件，如流动相中缓冲液的pH值，乙腈的比例，流动相中极性溶剂的比例等对印迹柱的特异选择性的影响，并优化了印迹柱的色谱条件。其中基于POSS的液晶MIP毛细管涂层柱手性拆分分离度高达22.3，相对于不加POSS时的印迹柱提高了两倍。本项目我们从传质动力学及板高分析等方面研究模板分子的传质机制；以前沿色谱、手性分离热力学及吸附模型表征其印迹位点的可接近性及不均匀性；总结聚合参数对新型MIP结构及性能影响的规律。实验中观察到如用手性分子做掺杂剂以外消旋分子做模板也能获得较好的印迹效果，由于液晶MIP在引入手性分子做掺杂剂后，使聚合物内部结构由排列规整的向列相变为螺旋形的胆甾相，因此能更好地保护印迹位点的完整性，增大印迹因子。该研究表明有望以廉价的外消旋分子代替光学纯分子做模板来制备高选择性的分子印迹手性固定相。