七元瓜环与阿德福韦衍生物的自组装体系研究

Study on the Self-assembly System of Cucurbit[7]uril with Adefovir Derivative

利用1HNMR、红外光谱、紫外吸收光谱、质谱及等温量热滴定(ITC)等方法分析了七元瓜环(Q[7])与阿德福韦单熊去氧胆酸-3-丙基酯,单L-异亮氨酸-3-丙基酯(X3I3)草酸盐的包合作用,并进行了自组装包结物的体外累积释放度研究和吸湿稳定性考察。结果表明,随着Q[7]比例的增大,体系内的主客体多种作用模式并存,甚至存在1个客体分子“挂满”4个Q[7]的包合物,波谱及ITC结果显示1.0∶1包合模式为稳定作用模式。在人工胃液中,Q[7]对X3I3草酸盐起到控释作用;在人工肠液中,Q[7]对X3I3草酸盐释放起到促进作用。X3I3与Q[7]形成的固体包结物的吸湿稳定性明显提高,常温、常湿条件下放置90 d仍然为白色固体。

The interaction properties and mechanism of host-guest of cucurbit[7]uril with adefovir mono L-isoleucine-3-propyl ester,mono ursodeoxycholic acid-3-propyl ester were investigated by 1HNMR,IR spectroscopy,UV absorption spectrum,high resolution mass spectrometry and isothermal calorimetry(ITC).Moreover,cumulative release in vitro and hygroscopic stability were evaluated.The experimental results revealed that cucurbit[7]uril can form host-guest complex with adefovir prodrug,and the inclusion ratio of Q[7]and X3I3 oxalate was related to the concentration of Q[7].As the molar ratio of Q[7]in the system increases,multiple action modes of host and guest coexisted in the system,and even existed an guest molecule“loaded”with four Q[7]clathrates,but only the 1.0∶1 mode was the most stable one.Studies on cumulative release in vitro showed that Q[7]play a controlling role in the release of X3I3 oxalate in artificial gastric juice,and it promoted the release of X3I3 oxalate in artificial intestinal fluid.The hygroscopic stability of the solid inclusion formed by X3I3 and Q[7]was significantly improved,and it remained white solid for 90 d under normal temperature and constant humidity.