论文标题
蓝色月亮合奏模拟的含水能源轮廓应用于单声道和双功能铂抗癌药物
Blue moon ensemble simulation of aquation free energy profiles applied to mono and bifunctional platinum anticancer drugs
论文作者
论文摘要
中性顺铂和阳离子单功能衍生物的含水游离能谱，包括三氨基氯铂（II）和顺式 - 二氨基氨基氨基氨基氨基氨酸（吡啶）叶绿素（II），使用ART热力学整合的状态进行了基于哪种温度和溶液的动力学canicity decticalitial doctial canical canony canon canon canon canon canon canon can on can can canon can can in can can in Art热力学整合，使用ART热力学整合进行计算。对于所有系统，已经观察到金属中心充当氢键受体的“反水合”。这促使在启动受约束的DFT-MD轨迹所需的反应坐标的定义中考虑反键合溶剂分子。我们发现，自由激活焓几乎没有差异，因此这些基于铂的抗癌药物在水性培养基中的行为可能相同。讨论了方形平面复合物的微覆盖结构的详细分析，以及含水机制的关键步骤。
Aquation free energy profiles of neutral cisplatin and cationic monofunctional derivatives, including triaminochloroplatinum(II) and cis-diammine(pyridine)chloroplatinum(II), were computed using state of the art thermodynamic integration, for which temperature and solvent were accounted for explicitly using density functional theory based canonical molecular dynamics (DFT-MD). For all the systems the "inverse-hydration" where the metal center acts as an acceptor of hydrogen bond has been observed. This has motivated to consider the inversely bonded solvent molecule in the definition of the reaction coordinate required to initiate the constrained DFT-MD trajectories. We found that there exists little difference in free enthalpies of activations, such that these platinum-based anticancer drugs are likely to behave the same way in aqueous media. Detailed analysis of the microsolvation structure of the square-planar complexes, along with the key steps of the aquation mechanism are discussed.
