基于密度泛函理论的荷叶碱分子反应活性位点分析

Analysis of Active Reaction Sites of Nuciferine Molecule Based on Density Functional Theory

目的:全面分析荷叶碱分子反应活性位点,为在分子水平阐明荷叶碱作用机理和构效关系,进一步推动荷叶碱结构改造和荷叶资源开发利用提供理论参考。方法:依据量子化学密度泛函理论,利用Gaussian软件优化荷叶碱分子结构,利用Multiwfn软件从分子表面静电势、前线分子轨道、原子电荷等方面对其反应活性位点进行计算分析。结果:荷叶碱分子甲氧基O(22)和苯环H(17)附近存在静电势最大值点和最小值点。叔胺N(39)原子附近具有分子表面静电势极小点(-29.72kcal/mol),具有较高负电荷(-0.284a.u.),较高f-值(0.098),且为HOMO轨道。结论:荷叶碱分子中甲氧基O(22)和苯环H(17)在易发生以静电吸引为主的反应;叔胺N(39)原子易发生亲电反应;苯环C(3)、C(5)易发生亲电取代反应。

Objective:To provide theoretical reference for elucidating the action mechanism and structure-activity relationship of nuciferine at the molecular level,and further promote the structural transformation of nuciferine and the development and utilization of lotus leaf resources,the molecular reactive active sites of nuciferine was comprehensively analyzed.Methods:According to quantum chemical density functional theory,the molecular structure of nuciferine was optimized by using Gaussian 09 software,and the reactive active sites were calculated and analyzed from several aspects such as surface electrostatic potential,frontline molecular orbital and atomic charge.Results:There are the maximum and minimum points of electrostatic potential near the methoxy O(22)and the benzene ring H(17)of the nuciferine molecule.Near the tertiary amine N(39)atom there is a minimum point of surface electrostatic potential(-29.72kcal/mol),it also has a higher negative charge(-0.284a.u.)and a higher f-value(0.098),and it is HOMO orbital.Conclusions:The methoxy O(22)and the benzene ring H(17)in the nuciferine molecule play an important role in the reaction dominated by electrostatic attraction.The N(39)atom of tertiary amine is the active site for electrophilic reaction,and the benzene ring C(3)and C(5)are prone to electrophilic substitution reaction.