抗癌新药CPA-7的水解活性的密度泛函研究

Density Functional Study on Aquation of the Anticancer Drug CPA-7

采用密度泛函理论的DFT方法,在B3LYP/6-31G(d,p)(除SDD用于Pt原子)理论水平上对抗癌药物CPA-7的两步水解反应机理从热力学和动力学方面进行了系统研究,三个水分子被引入到反应体系以提高反应体系的溶剂化能,我们的计算结果显示:构型A和B发生第一次水合过程的活化自由能分别为101.5和102.8kJ/mol-1,紧接着发生第二次水合过程的活化自由能分别为113.7和104.6kJ/mol-1,明显高于第一个过程,而且溶剂化效应使得活化势垒有所降低,该机理很好地解释了实验结果.

Using density functional theory （DFT）, the thermodynamics and the kinetics of the double aquation reaction for the anticancer drug CPA-7 was investigated by calculating.. Three explicit water molecules were included in the calculations to improve the solvation energies. Calculated activation free energy of the first aquation step were 101.5 and 102.8 kJ/mol 1 for A and B. The activation free ener- gy for the second aquation step were found significantly higher, the calculating value were 113.7 and 104.6 kJ/mol^-1 for A and B. The mechanisms have explained well the experimental results.