苯丁酸氮芥的七、八元瓜环包合物的稳定性研究

Study on the stability of inclusion compound of chlorambucil and cucurbit(n=7,8) uril

苯丁酸氮芥是一种良好的抗癌药物,但其在水溶液中溶解度低和易水解的特点,使得它的疗效和发展受到限制,瓜环可以包合小分子物质并改善小分子的理化性质,本实验采用分子模拟的方法对瓜环和苯丁酸氮芥包合物的稳定性进行了研究。首先利用分子力学的方法,确定苯丁酸氮芥与七、八元瓜环包合物的最稳定优势构型,在此基础上模拟一定时间内包合物的动态结构,统计苯丁酸氮芥包合前后结构的变化,计算结果表明:由于范德华力和氢键的作用,苯丁酸氮芥和瓜环包合后势能明显下降,证明了七、八元瓜环包合苯丁酸氮芥的包合物动力学上可以稳定的存在。

Chlorambucil is a good kind of anti-cancer drugs, but the efficacy and development is restricted because of its low solubility and ease hydrolysis in aqueous. Cucurbit can include small molecules and improve the physics and chemistry characteristics of the small molecules. This experiment studied the stability of inclusion of chlorambucil and cucurbit with the method of molecular simulation. First, use the methods of molecular dynamics to determine the most stable configuration of the inclusion, then simulate the dynamic structure of inclusion complexes in a certain time, statistic the structure changes before and after the simulation. The results show that： the potential energy of the inclusion decreased significantly due to van der Waals forces and the role of hydrogen bonds, the inclusion of chlorambucil and cucurbit can stable exist in dynamic.