摘要
目的研究大黄素与Al^(3+)、Fe^(3+)、Fe^(2+)、Cu^(2+)四种金属离子的配位作用,从配位化学角度探讨大黄素治疗阿尔茨海默症(Alzheimers disease,AD)的作用机理。方法采用GaussianView软件,设计大黄素与Al^(3+)、Fe^(3+)、Fe^(2+)、Cu^(2+)四种金属离子可能形成的配合物;采用Gaussian09软件,在HF/3-21G水平下,对配合物进行几何的优化和振动频率的分析,并在B3LYP/6-31G*水平下进行自然键轨道分析。结果大黄素与Al^(3+)、Fe^(3+)、Fe^(2+)、Cu^(2+)四种金属离子均可以形成1∶1和2∶1配比的配合物,这与已有的实验预测相吻合,除此之外,大黄素与Al^(3+)和Fe^(3+)还能形成3∶1配位的配合物,且3∶1配比的配合物具有较高的稳定性;金属离子与大黄素配位时,配位能力由大到小依次是:Al^(3+)> Fe^(3+)> Cu^(2+)> Fe^(2+)。结论基于前期文献调研和计算结果,本研究推测大黄素治疗AD的作用机理为:大黄素通过配位患者体内的Al^(3+)、Fe^(3+)、Fe^(2+)、Cu^(2+)等"金属离子外邪"从而除去AD"毒损脑络"之"内生毒邪"的产生。
Objective To study the coordination of emodin with Al3+,Fe3+,Fe2+,Cu2+,and to explore the mechanism of emodin in the treatment of AD from the perspective of coordination chemistry.Methods The possible complexes of emodin with four metal ions,Al3+,Fe3+,Fe2+,Cu2+,were designed by GaussianView.The geometry and vibrational frequencies of the complexes were calculated at the HF/3-21G level of the Gaussian09 package,and the natural bond orbita analysis was calculated at B3LYP/6-31G*level.Results Emodin and four metal ions could form complexes with coordination ratio of 1∶1 and 2∶1,which are consistent with the existing experimental prediction.In addition,emodin and Al3+,Fe3+could also form complexes with 3∶1 coordination ratio,which have higher stability compared with 1∶1 and 2∶1 complexes.And the coordination ability of metal ions with emodin was Al3+>Fe3+>Cu2+>Fe2+.Conclusion Based on previous literature research and quantum computational chemical results,the present study speculated that the mechanism of emodin of treatment of AD is:emodin could remove the“endogenous toxic”of"toxin damaging brain collaterals"by coordinating“exogenous metal ion”such as Al3+,Fe3+,Fe2+,Cu2+in AD patients.
作者
韩冬月
宋玲玲
关君
Han Dongyue;Song Lingling;Guan Jun(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2020年第3期829-835,共7页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会青年基金项目(81403069):基于计算量子化学和分子动力学模拟方法以SHP-2为靶分子研究雄黄抗肿瘤的药效物质和作用机理,负责人:关君
北京中医药大学科研发展基金项目(2019):矿物药及金属有机药物的配位-络合-配伍理论探索,负责人:关君。
