Methodological Approach Based on Structural Parameters, Vibrational Frequencies, and MMFF94 Bond Charge Increments for Platinum-Based Compounds

In this work, we performed a comprehensive benchmark study for the ground state of five small- and medium-sized platinum derivatives, PtH, PtCl, [PtCl4]2–, [Pt(NH3)4]2+, and cis-[Pt(NH3)2Cl2], in the gas phase and two cisplatin polymorphs in the solid phase. The benchmark encompassed 16 density functionals, including nonhybrids, hybrids, and double hybrids. Furthermore, Hartree–Fock (HF) and Post-HF by Møller–Plesset MP2 methods were also tested. Additionally, 11 basis sets were explored, comparing relativistic all-electron and RECP approaches. Our results indicate that the methodologies best suited for predicting structural parameters do not excel in predicting vibrational frequencies and vice versa. In the context of this theoretical framework, we also examine the derivation of partial atomic charges and bond charge increments (bci) as fundamental parameters within the MMFF94 classical force field. Our results show that the partial atomic charges of CHELPG present a slight charge fluctuation in Pt for all investigated levels of theory, and this behavior reproduces well the soft acid definition for Pt2+, giving the best description of the chemical environment of platinum in the cisplatin complex. The average calculated bci values effectively capture the atomic charge variations in the chemical environment of Pt in the investigated species. The developed bci optimization tool, based on MMFF94, was implemented using a Python code made available at https://github.com/molmodcs/bci_solver. This methodology will be further implemented in the DockThor receptor–ligand docking program, allowing future molecular docking validations involving ligand compounds containing Pt atoms.本研究针对五种中小型铂衍生物（气相中的PtH、PtCl、[PtCl₄]²⁻、[Pt(NH₃)₄]²⁺以及顺式-[Pt(NH₃)₂Cl₂]）与固相中的两种顺铂多晶型物的基态，开展了全面的基准测试研究。本次基准测试涵盖16种密度泛函（含非杂化泛函、杂化泛函与双杂化泛函），同时测试了哈特里-福克（Hartree–Fock, HF）方法与莫勒-普莱塞特MP2后哈特里-福克（Post-HF）方法。此外，本研究探索了11种基组，对比了相对论全电子基组与有效核势（Relativistic Effective Core Potential, RECP）两种计算方案。研究结果表明，最适于预测结构参数的计算方法，在振动频率预测方面表现欠佳，反之亦然。基于该理论框架，本研究还探讨了作为MMFF94经典力场核心参数的部分原子电荷与键电荷增量（bond charge increments, BCI）的推导方法。结果显示，在所有考察的理论方法下，CHELPG电荷均在铂原子上呈现轻微的电荷波动，这一现象与Pt²⁺的软酸定义吻合良好，可最佳描述顺铂配合物中铂的化学环境。计算得到的平均键电荷增量值，能够有效反映所考察物种中铂原子化学环境下的原子电荷变化情况。本研究基于MMFF94开发了键电荷增量优化工具，其Python实现代码已公开于https://github.com/molmodcs/bci_solver。该方法将进一步集成至DockThor受体-配体对接程序中，为未来开展含铂原子配体化合物的分子对接验证提供支撑。