基于密度泛函理论的卡博特韦分子反应活性位点预测

Prediction of Active Reaction Sites of Cabotegravir Molecule Based on Density Functional Theory

基于量子化学密度泛函理论,对卡博特韦分子表面静电势、平均局部离子化能、前线分子轨道、原子电荷及概念密度泛函活性指数进行计算分析。结果显示:卡博特韦分子羟基O(27)原子具有较多的Mulliken负电荷,附近具有分子表面静电势极小点,具有较多负电荷,较高f-值,为HOMO轨道。羰基O(24)及O(23)原子计算结果类似。研究表明:卡博特韦分子中羟基O(27)、羰基O(24)和O(23)原子为亲电反应活性位点,亲核反应的部位主要集中羰基C(14)、C(6)和C(9)原子上。在静电吸引中,羰基O(28)、羟基O(27)及亚甲基H(31)将发挥主要作用。

Based on quantum chemical density functional theory,the surface electrostatic potential,average local ionization energy,frontier molecular orbital,atomic charge and conceptual density functional activity index of cabotegravir were calculated and analyzed.The results showed that the hydroxyl O(27)atom of cabotegravir molecule had more Mulliken negative charge,and there was a minimum point of molecular surface electrostatic potential nearby,with more negative charge,the higher f-value,it also was HOMO orbital.Similar results were calculated for the carbonyl O(24)and O(23)atoms.Studies showed that the hydroxyl O(27),carbonyl O(24)and O(23)atoms in the cabotegravir molecule were electrophilic reactive sites,and the nucleophilic reaction sites were mainly carbonyl C(14),C(6)and C(9)atomically.In electrostatic attraction,carbonyl O(28),hydroxyl O(27)and methylene H(31)would play a major role.