衍生化环糊精修饰的纳米金粒子用于开管毛细管电色谱手性药物分离研究

项目名称： 衍生化环糊精修饰的纳米金粒子用于开管毛细管电色谱手性药物分离研究

项目编号： No.81473178

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郭兴杰

作者单位： 沈阳药科大学

项目金额： 70万元

中文摘要： 手性药物分离一直是分析化学家们面临的一个挑战。毛细管电色谱法（CEC）兼具毛细管电泳法（CE）的高分离效能和HPLC的高选择性，是功能强大的手性药物对映体分离技术。开管毛细管电色谱法(OTCEC)是CEC的重要分支，被认为是填充柱的理想替代模式，是当前CEC研究的热点。由于毛细管内表面积小，开管柱可涂布的固定相量少、相比低，致使样品分离效率低，制约了开管柱分离技术的应用和发展。本项目拟利用纳米金比表面积大，容易功能化的特点，采用新设计合成的衍生化环糊精（CDs）为手性选择剂，制备以CDs修饰的纳米金为涂层的开管毛细管电色谱柱。在此基础上，建立多种类型手性药物的对映体分离系统，结合光谱分析法和分子模拟技术判断主客体分子间的作用类型和结合位点，从分子水平上阐明其分离机理。本项目的实施，将推动毛细管电色谱分离技术的发展，提高手性药物对映体分离能力和水平，具有较高的学术意义和应用价值。

中文关键词： 对映体分离；毛细管电色谱；纳米粒子；衍生化环糊精；手性药物

英文摘要： The search for efficient and effective methods for enantioseparation of chiral drugs has always been the focus of chemists. Capillary electrochromatography (CEC), which combines the high efficiency of CE and the high selectivity of HPLC, exhibits great performance in chiral separation and has been extensively used. Open-tubular capillary electrochromatography (OTCEC), an important branch in CEC, provides advantages of ease of preparation, absence of bubble formation, and simple instrumental handling. But in OTCEC, superficial area of the inner face wall is small, and the amount of coating stationary phase is limited, resulting in relatively poor phase ratio and sample separation efficiency. Gold nanoparticles (GNPs) have their special characteristics of large specific surface area, easy formation of active complexes, and controllable particle size with narrow size distribution. They could compensate the lack mentioned above for OTCEC, and widen the application of OTCEC. In this research, GNPs will be modified by cyclodextrin derivatives (CDs), and these functionalized CD-GNPs are subsequently immobilized on capillaries as stationary phase for chiral separation. Enantioseparation systems of various kinds of chiral drugs will be established utilizing these prepared open-tubular capillaries. Then the host-guest interaction mode and inclusion binding site between CDs and chiral drug will be studied by means of spectrum methods and molecular modeling. The possible enantioseparation mechanism at the molecular level will also be discussed. The project will provide theoretical and practical support for establishing new enantioseparation platform of chiral drugs and promote the development of CEC technology.

英文关键词： Enantioseparation;Capillary Electrochromatography;Nanoparticles;Cyclodextrins;Chiral drugs