The formation of the Hg–N3(T) bond between the 1‐methylthymine (T) molecule and the hydrated Hg2+ cation was explored with the combined quantum mechanics/molecular mechanics (QM/MM) method including Free Energy Perturbation corrections. The thermodynamic properties were determined in the whole pH range, when these systems were explicitly investigated and considered as the QM part: (1) T + [Hg(H2O)6]2+, (2) T + [Hg(H2O)5(OH)]+, (3) T + Hg(H2O)4(OH)2, and (4) N3‐deprotonated T + Hg(H2O)4(OH)2. The MM part contained only solvent molecules and counterions. As a result, the dependence of Gibbs‐Alberty reaction free energy on pH was obtained along the reaction coordinate. We found that an endoergic reaction in acidic condition up to pH < 4–5 becomes exoergic for a higher pH corresponding to neutral and basic solutions. The migration of the Hg2+ cation between N3 and O4/2 positions in dependence on pH is discussed as well. For the verification, DFT calculations of stationary points were performed confirming the qualitative trends of QM/MM MD simulations and NMR parameters were determined for them.

中文翻译：

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QM 和 QM/MM 伞形采样 Hg(II)-胸腺嘧啶键形成的 MD 研究：评估恒定 pH 溶液中反应能量分布的模型

1-甲基胸腺嘧啶 (T) 分子和水合 Hg2+ 阳离子之间 Hg-N3(T) 键的形成是通过结合量子力学/分子力学 (QM/MM) 方法探索的，包括自由能扰动校正。当这些系统被明确研究并被视为 QM 部分时，热力学特性在整个 pH 范围内确定：(1) T + [Hg(H2O)6]2+，(2) T + [Hg(H2O)5 (OH)]+、(3) T + Hg(H2O)4(OH)2 和 (4) N3 去质子化的 T + Hg(H2O)4(OH)2。MM 部分仅包含溶剂分子和反离子。结果，沿反应坐标获得了 Gibbs-Alberty 反应自由能对 pH 值的依赖性。我们发现，在酸性条件下，pH < 4-5 的吸能反应对于对应于中性和碱性溶液的较高 pH 变得放热。还讨论了 Hg2+ 阳离子在 N3 和 O4/2 位置之间的迁移取决于 pH 值。为了验证，进行了驻点的 DFT 计算，确认了 QM/MM MD 模拟的定性趋势，并为其确定了 NMR 参数。