单双功能铂类抗癌药物水合自由能分布的蓝月亮系综模拟
Blue moon ensemble simulation of aquation free energy profiles applied to mono and bifunctional platinum anticancer drugs
摘要：
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-二氨（吡啶）氯铂（II）的水化自由能分布，计算使用最先进的热力学积分，其中温度和溶剂占明确使用密度泛函理论为基础的典型分子动力学（DFT-MD）。在所有体系中均观察到金属中心作为氢键受体的“逆水合”现象。这促使我们在定义反应坐标时考虑反向键合的溶剂分子，以启动受约束的DFT-MD轨迹。我们发现，在活化的游离分子量方面存在很小的差异，使得这些基于铂的抗癌药物在水性介质中可能以相同的方式表现。详细分析了平面正方形配合物的微观溶剂化结构，并讨论了水合机理的关键步骤。
英文摘要：
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.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
