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Blue moon ensemble simulation of aquation free energy profiles applied to mono and bifunctional platinum anticancer drugs
Journal of Computational Chemistry ( IF 3 ) Pub Date : 2020-06-26 , DOI: 10.1002/jcc.26367
Teruo Hirakawa 1, 2 , David R Bowler 3, 4, 5 , Tsuyoshi Miyazaki 5 , Yoshitada Morikawa 1, 6, 7 , Lionel A Truflandier 1, 2
Affiliation  

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 activation, 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, is discussed.

中文翻译:

应用于单功能和双功能铂抗癌药物的水化自由能分布的蓝月系综模拟

使用最先进的热力学积分计算了中性顺铂和阳离子单官能衍生物(包括三氨基氯铂(II)和顺式二胺(吡啶)氯铂(II))的水合自由能分布,其中使用密度明确地考虑了温度和溶剂基于泛函理论的经典分子动力学(DFT-MD)。对于所有系统,都观察到金属中心充当氢键受体的“逆水合”。这促使在定义启动受限 DFT-MD 轨迹所需的反应坐标时考虑反键溶剂分子。我们发现自由活化焓几乎没有差异,因此这些铂类抗癌药物在水性介质中的表现可能相同。
更新日期:2020-06-26
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