Computational predictions of metal–macrocycle stability constants require accurate treatments of local solvent and pH effects
Computational predictions of metal–macrocycle stability constants require accurate treatments of local solvent and pH effects
复制标题
金属大环稳定性常数的计算预测需要准确处理局部溶剂和 pH 影响
DOI：
10.1039/d1cp00611h
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发表时间：
2021
影响因子：
3.3
通讯作者：
Keith, John A.
中科院分区：
文献类型：
--
作者：
Gentry, Brian M.;Choi, Tae Hoon;Belfield, William S.;Keith, John A.
合理设计分子螯合剂需要详细了解溶剂相中配体-金属的物理化学相互作用。计算量子化学方法应该能够提供这一点，但计算报告显示，在确定许多螯合分子的绝对结合常数时，准确性较差。为了理解为什么，我们比较并基准静态和动态为基础的计算程序的一系列单价和二价阳离子结合到一个传统的穴状配体分子：2.2.2-穴状配体（[2.2.2]）。基准比较表明，动力学模拟使用标准OPLS-AA经典电位可以合理地预测结合常数为一价阳离子，但这些程序失败的二价阳离子。我们还考虑计算效率的静态程序，使用Kohn-Sham密度泛函理论（DFT）和集群连续建模，占局部微溶剂化和pH值的影响。与实验相比，这种方法准确地预测了一价和二价阳离子的结合能，平均误差为3.2 kcalmol-1。因此，这种静态的程序应该是有用的，为未来的分子筛选工作，在文献中的高绝对误差可能是由于局部溶剂和pH值的影响建模不足。
Rational design of molecular chelating agents requires a detailed understanding of physicochemical ligand–metal interactions in solvent phase. Computational quantum chemistry methods should be able to provide this, but computational reports have shown poor accuracy when determining absolute binding constants for many chelating molecules. To understand why, we compare and benchmark static- and dynamics-based computational procedures for a range of monovalent and divalent cations binding to a conventional cryptand molecule: 2.2.2-cryptand ([2.2.2]). The benchmarking comparison shows that dynamics simulations using standard OPLS-AA classical potentials can reasonably predict binding constants for monovalent cations, but these procedures fail for divalent cations. We also consider computationally efficient static procedure using Kohn–Sham density functional theory (DFT) and cluster-continuum modeling that accounts for local microsolvation and pH effects. This approach accurately predicts binding energies for monovalent and divalent cations with an average error of 3.2 kcal mol−1 compared to experiment. This static procedure thus should be useful for future molecular screening efforts, and high absolute errors in the literature may be due to inadequate modeling of local solvent and pH effects.