目的:采用量子化学计算方法进一步确定乌头碱的代谢产物结构。方法:采用密度泛函方法,在B3LYP/6-31G(d)水平上,对代谢产物的结构进行优化,在此基础上计算反应物和产物的能量,用以比较水解反应能量,并采用IEFPCM方法进行了溶剂效应计算。结果:分别比较4种可能产物的反应能量,确定乌头碱代谢产物有16-O-去甲基乌头碱和16-O-去甲基乌头次碱,水溶液中不同产物的能量差增大,进一步证实了产物的合理性。结论:量子化学计算的代谢产物与根据多级质谱裂解规律推测的结果相同,量子化学计算与HPLC-MSn结合,可为乌头碱代谢产物和代谢规律的研究提供依据。

The study is aimed to identify metabolites of aconitine by quantum chemistry calculation.Geometries of possible metabolites were optimized by using density functional theory(DFT) at B3LYP/6-31G(d) level.Energy of possible metabolites and hydrolysis reactions were obtained.Solvation effects were calculated by using IEFPCM.Comparison among four possible reaction energies showed that metabolites of aconitine were identified as 16-O-demethylaconitine and 16-O-demethylbenzoylaconine.Energy difference of possible metabolites was increased in aqueous solution.It is concluded that metabolites identified by quantum chemistry calculation is the same as results deduced by fragmentation regularity of mass spectrometry.Metabolites of aconitine can be studied by a combination of HPLC-MSn and quantum chemistry calculation.

国家自然科学基金课题青年项目(30901959):基于质谱裂解规律预测乌头碱型生物碱Ⅰ相代谢产物的研究,负责人:刘永刚;科学技术部国家“973”计划项目(2009CB522800):确有疗效的有毒中药科学应用关键问题的基础研究,负责人:叶祖光