七、八元瓜环对氯氮平的包合和增溶作用

Solubilization and inclusion of clozapine by cucurbit [n=7,8] urils in aqueous solution

目的:研究七元瓜环(Q[7])、八元瓜环(Q[8])与氯氮平(CLP)的超分子包合作用及包合物的溶解性能。方法:利用紫外光谱、1 H-NMR等技术研究Q[7]、Q[8]与CLP的主-客体包合作用。测定了Q[7]-CLP、Q[8]-CLP的包合作用pH敏感性、包合比、包合稳定常数及包合物的溶解性能。结果:Q[7]-CLP、Q[8]-CLP体系的超分子包合作用均具有pH敏感性,包合比分别为1∶1与1∶2,Q[7]-CLP和Q[8]-CLP的包合平衡常数分别为2.5×10~4 L·mol^(-1)和8.0×10~3 L·mol^(-1),Q[7]-CLP和Q[8]-CLP的溶解性分别比CLP提高了90倍和14倍。结论:Q[7]及Q[8]包合对CLP有明显的增溶作用。

OBJECTIVE To investigate the supermolecular inclusion of cucurbit[7,8]urils with clozapine（CLP）and solubility of inclusion complexes.METHODS Solubility,pH sensitivity,inclusion ratio and stability constant of inclusion complexes of Q[7,8]-CLP system were determined with 1 H-NMR technique and UV-Vis spectroscopy.RESULTS The interaction of host-guest inclusion complexes was pH sensitive.The inclusion ratios between host molecular and Q[7]-CLP or Q[8]-CLP were 1∶1 and1∶2,respectively.Stability constants of inclusion complexes of Q[7]-CLP and Q[8]-CLP were 2.5×10^4 L·mol^（-1）and 8.0×10^3 L·mol^（-1）,respectively.The solubilities of Q[7]-CLP and Q[8]-CLP were increased by 90 and 14 times than that of CLP,respectively.CONCLUSION The solubility of Q[7]-CLP and Q[8]-CLP is significantly improved than the original drug CLP.