Jorgensen William L, Tirado-Rives Julian
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.
J Phys Chem B. 2025 Jul 3;129(26):6574-6583. doi: 10.1021/acs.jpcb.5c02405. Epub 2025 Jun 18.
Free energies of solvation in liquid benzene and hexafluorobenzene have been computed for 42 uncharged solutes. Monte Carlo statistical mechanics was used with the free-energy perturbation theory and the OPLS-AA force field. The results address the transferability of the potential functions developed for pure liquids to mixed systems and the potential importance of explicit polarization for neutral organic molecules in aromatic solvents. Although the free-energy results cover an 11 kcal/mol range, the average error in comparison with experimental data points is only 0.4 kcal/mol. There is no systematic pattern to the discrepancies, so the need to add explicit treatment of solute-solvent polarization effects is not supported. This contrasts the situation with cationic solutes as reflected in cation-π interactions. Results for free energies of hydration are also provided for the 42 solutes in TIP4P water and give an average error of 0.49 kcal/mol. Implications for modeling biomolecular systems with standard force fields are considered. It is also interesting to note the overall similar values for free energies of solvation in benzene and hexafluorobenzene despite the reversal of polarity for the aromatic rings; the most significant exception is the more favorable solvation of perfluoroalkanes in the perfluoro solvent. Alternative accommodations of solutes in the two solvents are illustrated.
已计算了42种不带电荷溶质在液态苯和六氟苯中的溶剂化自由能。采用蒙特卡罗统计力学结合自由能微扰理论和OPLS - AA力场。结果涉及为纯液体开发的势函数对混合体系的可转移性，以及芳香族溶剂中中性有机分子明确极化的潜在重要性。尽管自由能结果涵盖了11千卡/摩尔的范围，但与实验数据点相比，平均误差仅为0.4千卡/摩尔。差异没有系统的模式，因此不支持添加溶质 - 溶剂极化效应的明确处理的必要性。这与阳离子溶质在阳离子 - π相互作用中所反映的情况形成对比。还给出了42种溶质在TIP4P水中的水合自由能结果，平均误差为0.49千卡/摩尔。考虑了用标准力场对生物分子系统进行建模的影响。同样有趣的是，尽管芳香环的极性发生了反转，但苯和六氟苯中溶剂化自由能的总体值相似；最显著的例外是全氟烷烃在全氟溶剂中的溶剂化更有利。说明了溶质在两种溶剂中的不同容纳方式。
