基于离子液体的毛细管电泳手性拆分新体系研究

Enantiomeric separation has received increasing attention. However, the enantiorecognition capability of single chiral separation system in capillary electrophoresis (CE) is limited, and the amount of conventional chiral selectors is still small. Therefore, it is of great importance to develop and discover novel chiral reagents, and to explore new separation systems in CE by the modification of conventional systems. Ionic liquids (ILs)，as new material, have drawn great attention. However, only more than ten literatures focused on the application of ILs in CE chial separation. In this project, novel ILs-based CE chiral separation systems will be systematically studied: self-design and synthesis of chiral ILs; development and discovery of novel ILs chiral selectors; study and establishment of chiral ILs synergistic separation systems and achiral ILs modified separation systems baesd on conventional chiral selectors (polysaccharides, antibiotics and cyclodextrins); development of ligand-exchange CE chiral separation systems with chiral ILs as chiral ligands and micellar electrokinetic chromatographic enantioseparation systems with ILs surfactants. Furthmore, research on the chiral recognition mechanism will be carried out by computer molecular simulation, CE method and spectroscopic analysis, so as to speculate the discovery of novel CE separation system and the enantioseparation of drugs. The enantioseparation and optical purity test of new chiral drugs will also be performed. The project presents high-level of academic value, and is of great importance in practical application.

手性药物的拆分已得到广泛关注，然而单一手性选择剂手性识别能力及种类有限，因此，对传统拆分系统进行修饰，研制和发现新型手性识别材料，开展毛细管电泳（CE）手性拆分新体系研究，意义重大。离子液体作为一种新型材料，已成为当前研究热点，而在CE手性拆分领域，其相关研究仅十余篇文献报道，存在很大研究空白。本项目拟系统开展基于离子液体的CE手性拆分新体系研究，自主设计并合成手性离子液体，研制或发现新型离子液体手性选择剂，研究并构建基于传统手性选择剂（多糖、抗生素、环糊精）的手性离子液体协同拆分体系和非手性离子液体修饰拆分体系、手性离子液体配体交换拆分体系及离子液体胶束电动毛细管色谱拆分体系。采用计算机分子模拟，结合CE和光谱分析法从分子水平上研究手性识别机理，辅助新型CE拆分体系的发现和构建，评估手性药物拆分的可能性。研究成果直接用于创新药物的CE拆分和光学纯度检查，具有较高的学术意义和应用价值。

手性药物的拆分已得到广泛关注，然而单一手性选择剂手性识别能力及种类有限，因此，对传统拆分系统进行修饰，研制和发现新型手性识别材料，开展毛细管电泳（CE）手性拆分新体系研究，意义重大。离子液体作为一种新型材料，已成为当前研究热点，而在CE手性拆分领域仍存在很大研究空白。在本项目中，我们成功研制开发了2个新型离子液体手性选择剂，研究构建了一系列性能优越的基于传统手性选择剂的手性离子液体协同拆分体系、非手性离子液体修饰拆分体系、手性离子液体配体交换拆分体系、离子液体胶束电动毛细管色谱拆分体系，取得了创新性的研究成果；采用计算机分子模拟，结合毛细管电泳和光谱分析方法从分子水平上对手性识别机理进行了研究，也取得了具有一定创新性的研究成果。建立了新药的光学纯度检查方法，并用于实际样品的光学纯度分析。本项目的完成有助于推动毛细管电泳手性选择剂以及毛细管电泳手性拆分新系统的发展，促进单一对映体新药的研制，具有较高的学术意义和实用价值。