Nonpublic Medical College in Wrocław, Nowowiejska 69, 50-340, Wrocław, Poland.
J Mol Model. 2011 Sep;17(9):2411-21. doi: 10.1007/s00894-011-1060-1. Epub 2011 May 11.
The search was made for theoretical confirmation of hypothesis that mechanism of cisplatin cytotoxicity is based on dissociative electron transfer (ET) processes. Applying quantum chemical calculations based on supermolecular approach, the reactions mimicking presumed steps of cisplatin activation were evaluated. The electronic structure of model systems: cis- and transplatin with free electrons, hydrated electrons, and water, was studied by using density functional (DFT) within the Huzinaga basis set and GAUSSIAN-09 package. The respective energy was evaluated with the use of B3LYP density hybrid functional. The calculations were performed for gas phase and water solution; the solvent effects were studied by using the polarizable continuum model. Analysis of the energetic and structural parameters of cisplatin vs. transplatin behavior in the model systems leads to conclusion: there are two possible ways of cisplatin biotransformation, hydrolysis and hydrated electron impact, dependent on the medium redox state.
本次搜索旨在从理论上证实假说，即顺铂细胞毒性的机制基于离域电子转移（ET）过程。应用基于超分子方法的量子化学计算，评估了模拟顺铂激活假定步骤的反应。通过使用密度泛函（DFT）在 Huzinaga 基组和 GAUSSIAN-09 包内，研究了模型体系中顺式和反式铂与自由电子、水合电子和水的电子结构。分别使用 B3LYP 密度杂化函数评估相应的能量。在气相和水溶液中进行了计算；通过使用极化连续模型研究了溶剂效应。对模型体系中顺铂与反铂行为的能量和结构参数的分析得出结论：顺铂的生物转化有两种可能的途径，即水解和水合电子冲击，这取决于介质的氧化还原状态。
