密度泛函法研究抗癌性钌配合物NAMI-A酸性条件下水解机理

A DFT Study on the Hydrolysis Mechanism of the Anticancer Complex NAMI-A under Acidic Condition

用量子化学密度泛函(DFT)方法,研究了第一个进入临床的抗癌性钌配合物[ImH][trans-RuCl4(DMSO)(Im)](NAMI-A)在酸性条件下的第一步水解反应。气相中,在UB3LYP/(LanL2DZ+6-31G(d))水平上对水解反应中各中间体、过渡态进行几何结构和振动频率的计算与分析。随后,用更高级基组,即在UB3LYP/(LanL2DZ(f)+6-311++G(3df,2pd)水平上进行单点能计算,并采用CPCM模型考虑溶剂化效应。通过计算不仅获得了反应中相关的几何和电子结构特征及详细的反应势能面,还得出酸性条件下,NAMI-A中的DMSO基团易于水解,同时伴随着Cl缓慢水解的结论,这与实验结果相吻合。该研究工作可为深入理解抗癌性钌配合物NAMI-A的水解机理提供有意义的理论参考。

The density functional theory（DFT） combined with the conductor-like polarizable calculation model（CPCM） was used to investigated the first hydrolysis step under acidic condition of a Ru（III） complex [trans-RuCl4（DMSO）（Im）]（NAMI-A） and the first ruthenium anticancer complex that has entered clinical testing.Full geometry optimizations and frequency calculations for each transition states and intermediate species were carried out at the UB3LYP/（LanL2DZ＋6-31G（d）） level in gas phase.Single-point energies were calculated at the UB3LYP/（LanL2DZ（f）＋6-311＋＋G（3df,2pd） level based on the optimized structures in acidic solution.The geometrical and electronic structures,and detailed energy profiles during the hydrolysis processes of the complex were investigated.It was found interestingly that the hydrolysis of DMSO ligand in acidic solution has thermodynamic preference over the hydrolysis of Cl atom,which was in good agreement with the experimental results.Thus this work can offer a significant theoretical reference for deeply understanding the hydrolysis mechanism of NAMI-A.