手性蜂窝状胶束材料及其对手性药物分离的研究

Chiral polymer material is widely applied in chiral drug separation because of its diverse chiral centers and configurations. At present, most of the materials applied in chiral separation are small chiral molecular surfactants and only a few are polymer materials polymerized by small chiral molecular surfactants. Studies on the application of micelle materials formed by chiral amphiphilic polymers to pseudostationary phases have not yet researched, where chiral amphiphilic polymers show superiority in variety of chiral center compositions and configurations. Based on the above issue, this project will systematically explore the preparation, structure and performance of chiral honeycomb micelle materials for drug separation. The separation process was based on the different strength（such as clathration,π-π effect, hydrogen bond, steric hindrance, van der waals force and synergistic effect）of chiral centers and the racemic drugs, and was carried out by Micellar Electrokinetic Capillary Chromatography and adsorption-ultrafiltration methods. In this project, we will also study the effects of material composition, configuration, morphology and external conditions such as temperature, pressure, pH value, and concentration on drug seperation to reveal the process and mechanism of resolution, explore new ways to enhance resolution selectivity and efficiency, as well as develop new theories and methods to separate chiral drugs.

手性高分子材料具有手性中心及形态多样化的特点，在手性药物分离领域有广泛的应用。目前用于手性分离的胶束材料绝大部分为手性小分子表面活性剂，只有少数为由手性小分子表面活性剂聚合得到的高分子材料，而以手性中心和结构形态更加多样化的手性两亲性聚合物形成的胶束材料用于准固定相的研究还是空白。针对上述问题，本项目拟系统探索具有手性药物分离功能的手性蜂窝状胶束材料的制备、结构与性能，利用胶束中的手性中心与外消旋药物间不同强度的亲和作用(如包合作用、π-π作用、氢键、立体排斥、范德华力及协同作用等)，借助于毛细管胶束电动色谱和吸附-超滤的方式实现对外消旋体的识别与分离；研究该类胶束材料的组成、结构、形态及外界拆分条件如温度、压力、pH值、浓度等对药物分离的影响，揭示拆分的过程和机理，探索提高拆分选择性和效率的手段，发展手性药物分离的新理论与新方法。

聚合物自组装制备的胶束粒子用于手性分离的研究较少，本项目立足于手性胶束粒子的制备及其对手性化合物的识别与分离研究，主要研究内容包括：1）合成了基于β-环糊精和多种氨基酸的手性单体，大分子单体等；2）合成了几种末端带有羧基和炔基的链转移剂（CTA）；3）利用自由基聚合和RAFT聚合制备多种含β-环糊精和氨基酸基的聚合物，尝试结合“点击”化学法和扩链法制备多种嵌段聚合物；4）RAFT聚合一步法制备胶束粒子，得到稳定的核层交联、不交联的胶束粒子，并通过吸附-脱附-超滤的方式实现了对D/L苯丙氨酸的识别与分离；5）制备手性水凝胶，利用吸附-脱附的方式实现对手性化合物的分离；6）利用“点击“化学反应在色谱硅胶表面接枝手性聚合物，通过加压过滤实现对手性化合物的分离。通过研究发现，手性胶束对对映体具有不同的吸附作用，可以用于手性化合物的拆分，对胶束粒子用于手性识别和拆分的研究具有一定的指导作用。