NAMI-A型钌配合物（HL）（trans—RuCl4L（dmso—s）]（L=1-methyl-1，2，4-triazole）水解机理的理论研究

Hydrolysis Mechanism of the NAMI-A-type Antitumor Complex （HL）[trans-RuCl4L（dmso-S）] （L=1-methyl-l,2,4-triazole）

用量子化学密度泛函方法结合导体极化连续模型研究了具有潜在抗肿瘤活性的NAMI—A型钉配合物（HL）[trans—RuCl4L（dmso．s）1（L=1—methyl-1，2，4-triazole，dmso-S=S—dimethylsul foxide）（1）的水解反应过程．计算得到该配合物水解反应过程中相应的结构特征和详细的反应势能面．对于第一步水解，液相中配合物1的活化能垒比已经报道的抗肿瘤药物（Him）[trans—RuCl4（dmso-S）（im）1（NAMI—A，im=imidazole）的活化能垒稍高，这与实验中显示配合物1的水解反应的半衰期稍大的结果相吻合．对于第二步水解，反应在热力学上优先生成顺式双水解产物．另外，通过对水解反应过程中各平衡构型的电子结构特征的分析，预示了水解产物被生物分子靶标亲核进攻能力的倾向．

The hydrolysis process of Ru（III） complex （HL）[trans-RuC14L（dmso-S）] （L=l-methyl-l,2,4- triazole and dmso-S=S-dimethyl sulfoxide） （1）, a potential antitumor complex similar to the well-known antitumor agent （Him）[trans-RuC14 （dmso-S）（im）] （NAMI-A, im=imidazole）, was investigated using density functional theory combined with the conductor-like polarizable continuum model approach. Tile structural characteristics and the detailed energy profiles for the hydrolysis processes of this complex were obtained. For the first hydrolysis step, complex 1 has slightly higher barrier energies than the reported anticancer drug NAMI-A, and the result is in accordance with the experimental evidence indicating larger half-life for complex 1. For the second hydrolysis step, the formation of cis-diaqua species is thermodynamic preferred to that of trans isomers. In addition, on the basis of the analysis of electronic characteristics of species in the hydrolysis process, the trend in nucleophilic attack abilities of hydrolysis products by pertinent biomolecules is revealed and predicted.