分子印迹膜内手性通道的构建及其结构调控的研究

In traditional membrane chiral separation processes, the separation efficiency deteriorates with the saturation of chiral selectors immobilized in the membrane. To address this issue, we propose to adopt a different separation mechanism and redesign the membrane, synergizing both molecular imprinting technology and membrane formation mechanism of block copolymer via self-assembly, in such a way to construct chiral selective channels within the selective layer of a membrane. Good enantioselectivity can be obtained by optimizing the channel structure by varying the experimental conditions. The main focus of this project is to investigate the relationship between the structure of the chiral channels and the membrane formation conditions, i.e. the properties of the polymer, imprinting molecules, solvents, concentration ratio, temperature and the strength of external electric field if any. Furthermore, the chiral pharmaceutical resolution efficiency of the as-prepared membrane is to be tested using tryptophan as the model molecule. As the separation mechanism of the chiral channel is facilitating selectively the transport of one enantiomer while rejecting the other, instead of retarding the transport of the enantiomer with higher affinity (as in the case of affinity filtration), the chiral selector, in this case the chiral channel, is not going to be saturated. Thus the problem of the selectivity decline can be solved and the membrane can operate with long term stability. The success of this study is not only going to provide new ideas and theoretical foundation for future research, but is also going to fabricate highly enantioselective membranes for the pharmaceutical industry, assisting the R&D and production of the active pharmaceutical ingredients. The cost of pharmaceuticals, and therefore the cost of medication can be reduced, such that the wellbeing of the people can be enhanced.

传统的“吸附－分离”型手性膜过程中，分离效率会随着手性选择剂的吸附饱和而逐渐降低。为解决这一问题，本项目应用不同的分离机理来设计手性分离膜，利用分子印迹技术和嵌段共聚物自组装成膜技术，在膜选择层中构建手性通道，并通过调节实验条件控制通道结构，制备出有效的手性分离膜。本项目将重点研究手性通道的成型及其结构与成膜聚合物、印迹分子、溶剂、浓度比、温度以及外加电场等的关系，总结出分子印迹技术构建手性通道的普适性方法；其次，将以色氨酸为模型分子，研究新型膜对于手性药物的拆分效率。该膜能选择性传递（而非吸附）对应的药物异构体，避免了吸附饱和的问题，因此能长期稳定运行。通过本项目的研究，不仅能为手性分离膜的进一步研究提供新的思路和理论基础，并且可望制备出高效的手性分离膜，应用到手性药物的研发和生产中，以起到节约成本、提高产量的作用。这对于降低药物价格，减轻百姓医疗负担，提高人民生活质量都具有积极意义。

本研究针对传统手性分离过程中，分离效率随手性选择剂吸附饱和而逐渐降低的问题，从分离机理的设计出发，利用界面聚合技术，将环糊精、DNA和BSA这三类手性选择剂引入到选择层中构建手性通道，并通过对聚合物浓度、手性选择剂种类、助剂类别、温度等条件的优化制备出了有效的手性分离膜。以色氨酸为模型分子，通过实验证明了该类复合薄膜的分离机理与传统的“吸附-分离”机理不同，手性选择剂构建的传输通道能促进与之相互作用力更强的手性分子（L-色氨酸）的传递，而非通过吸附作用来降低L-色氨酸的通量。在较长时间（>24h）实验中，手性选择性能维持不变，可见本研究制备的复合薄膜可以避免吸附饱和的问题，达到了项目的预期目标。同时，通过两种压滤和渗透这两种膜过程的比较，本研究总结出：当手性分离选择层的传递阻力越大，驱动力越小的时候，手性选择剂促进传递的现象越显著。综上，本研究对手性分离膜的制备进行了理论创新，制备了运用促进传质分离机理的复合薄膜，为手性分离膜以及其他超滤、纳滤膜的制备提供了新思路和理论基础。尽管本研究的成果暂时还无法直接应用，后续研究的分离膜若能进一步提高选择性，将能应用到手性药物的研发和生产中，这对降低医药成本，减轻人们医疗负担，提高生活水平都具有积极意义。