硫普罗宁药物的葫芦脲包合物稳定性研究  

A Molecular dynamics research:inclusive stability investigation on cucurbituril[n](n=7,8) complexes with tiopronin

作　　者：刘立[1] 李代禧[1] 余华星[1] 翟振[1] 张燕[1] 刘宝林[1] 

机构地区：[1]上海理工大学食品科学与工程研究所,上海200093

出　　处：《计算机与应用化学》2014年第6期760-762,共3页Computers and Applied Chemistry

基　　金：上海市重点学科项目(T0503和P0502);上海市"创新行动计划"国际科技合作项目(12430702000);上海市自然科学基金(12ZR1420400);上海市联盟计划项目和上海理工大学人文社会科学基金项目(11XSY23)

摘　　要：近年来,随着超分子化学的迅猛发展,环糊精、葫芦脲等物质在药学方面的应用日趋受到关注。色谱技术的发展,也使得药物分子的分离纯化技术有了很大提升。本文利用分子动力学模拟和Gaussian量子化学计算,分析硫普罗宁对映体的葫芦脲[n](n=7,8)包合物在常温下的动态结构稳定性和热力学稳定性,以期研究葫芦脲在亲和色谱分离时作为固定相的可能性。在真空条件下,通过分析包合物在常温时的动态结构、包合物的氢键作用和热力学分析结果可知,葫芦脲[月](n=7,8)可以包合硫普罗宁对映体,2个硫普罗宁对映体-葫芦脲[7]包合物的稳定性高于2个硫普罗宁对映体-葫芦脲[8]包合物。因此,葫芦脲[7]可以用于亲和富集2个硫普罗宁对映体,但不能有效地拆分硫普罗宁对映体;而葫芦脲[8]对2个硫普罗宁对映体包合作用尽管稍小,但差异性非常明显,故葫芦脲[8]有望作为1个有效的亲和色谱手性剂使用,用于拆分硫普罗宁对映体。With the rapid development of supramolecular chemistry,cyclodextrin and cucurbituril have been widely used in medical science.The development of chromatography technology has made great contributions to the improvement of separation and purification on drug.In current research,molecular dynamics simulation and Gaussian quantum chemical calculation were used to investigate the dynamic structure and thermodynamic stability of cucurbituril [n] （n=7,8） with tiopronin at room temperature,with respect to researching the possibility of cucurbituril used as stationary phase during affinity chromatography.By analyzing the dynamic structure,H-bond interactions and the thermodynamics properties of inclusion,the results revealed that cucurbituril [h] （n=7,8） inclusions with tiopronin could be formed,and the inclusive stability of cucurbituril [n] （n=7） inclusions with tiopronin were much more stable than that of the cucurbituril [n] （n=8） inclusions with tiopronin.So cucurbituril [n] （n=7） can be used for affinity enrichment of tiopronin,but it can＇t effectively perform the chiral separation.However,the inclusive stable differences between RTP-CB[8] and STP-CB[8] inclusion are obvious,although the cucurbituril [n] （n=8） inclusions with tiopronin inclusions have the lower stability,which suggests that cucurbituril [n] （n=8） can be used as chiral separation reagent in affinity chromatography to separate tiopronin enantiomers.

关 键 词：葫芦脲 硫普罗宁 稳定性 分子动力学 热力学 

分 类 号：TQ015.9[化学工程] TP391.9[自动化与计算机技术—计算机应用技术]