用量子化学密度泛函理论(DFT),并结合导体极化连续模型(CPCM)研究了具有潜在抗肿瘤活性的"Keppier型"钌配合物trans-[Ru~ⅢCl_4(2-NH_2-5-Me-STz)2](1)的水解反应过程.首先,在UB3LYP/(LanL2DZ+6-31G(d))理论水平上对水解反应中各平衡构型在气相条件下的有关结构进行全几何优化及振动频率分析;然后,在更高的基组水平LanL2DZ(f)+6-311HG(3df,2dp)上对优化的结构进行单点能计算,并考虑溶剂效应.计算得到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的活化能垒为92.9 kJ·mol~(-1),与已经报道的配合物trans.[Ru~ⅢCl_4(2-NH_2-Tz)_2](2)的活化能垒(96.3 kJ·mol~(-1))相接近,并与实验结果相符.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,恰如顺铂的水解反应机理一样,存在着所谓"顺式效应".即生成的顺式水解产物有利于其与生物分子靶标的键合,因此,顺式双水解产物在生物反应中有望成为重要的前体药物.本文研究结果有助于深入理解抗癌性Ru(Ⅲ)配合物与相关生物靶标的作用机理.%The hydrolysis of a potential antitumor Ru(Ⅲ) complex trans-[Ru~ⅢCl_4(2-NH_2-5-Me-STz)_2](1) was investigated using density functional theory (DFT) combined with the conductor-like polarizable calculation model (CPCM). Full geometry optimizations and frequency calculations in vacuo for each related equilibrium geometry were carried out at the UB3LYP/(LanL2DZ+6-31G(d)) level. Single-point energies were calculated in the gas phase and in solution at the UB3LYP/(LanL2DZ(f)+6-311++G(3df,2dp) level on the optimized structures. The structural characteristics and detailed energy profiles for the hydrolysis processes of this complex were obtained. For the first hydrolysis step,complex 1 has an activation energy of 92,9 kJ·mool~(-1) in solution and this is similar to that of the reported Ru(Ⅲ) complex trans-[Ru~ⅢCl_4(2-NH_2-Tz)_2](2) (96.3 kJ·mol~(-1)) and is in good agreement with experimental results, For the second hydrolysis step, the formation of cis-diaqua products is found to be thermodynamically preferred over the trans isomers. Similar to the hydrolysis action mechanism of cisplatin, a "cis effect" is present wherein the cis-diaqua products prefer binding to pertinent biomolecular targets. Therefore, cis-diaqua products can be expected to be important precursors for biological actions. These theoretical results should help in understanding the action mechanism of these potential Ru(Ⅲ)drugs with pertinent biomolecular targets.
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