Department de Chimie, Université de Montréal, CP 6128, Succursale Centre-Ville, Montréal H3C3J7, Canada.
J Chem Phys. 2010 Feb 21;132(7):074112. doi: 10.1063/1.3317398.
We introduce a novel approach to compute dissociation free energy and entropy values in simulations that employ a density functional theory description of the acidic moiety and of the solvent. The approach consists of utilizing an alchemical transformation of a weak acid A-COOH into the strong acid B-COOH, which makes it practical to employ alchemical free energy perturbation methods in the context of ab initio molecular dynamics simulations. The present alchemical transformation circumvents the need to tackle changes in the total number of electrons and atoms by replacing the chemical residue responsible for the change in acidity with an easily tunable external effective potential. Our investigation demonstrates that (1) a simple but effective class of external potentials that control acidity changes in the acetic/trifluoroacetic acid series can be achieved by replacing the methyl and trifluoromethyl substituents by screened dipoles. Using this dipole-field/quantum-mechanics (DF/QM) approach one can predict gas-phase geometries, proton dissociation energies, total dipole moments, and water binding energies in good agreement with full-QM values. (2) The resulting alchemical perturbation calculations are stable and well converged and allow one to compute absolute pK(a) values whose accuracy is limited primarily by the exchange-correlation functional employed: H-COOH=2.5+/-0.6 (full-QM calculation), 3.7 (exp); F(3)C-COOH=0.4+/-0.6 (DF/QM calculation), 0.5 (exp); H(3)C-COOH=3.1+/-0.7 (DF/QM calculation), 4.7 (exp); 3) Our DF/QM model predicts that the difference in acidity between H-COOH and H(3)C-COOH is dominated by solvent entropy effects, in excellent agreement with experimental observations. The calculated difference between the dissociation energies of these acids is DeltaDelta(d)U=0.0+/-0.26 kcal/mol while the experimental value is 0.0+/-0.1 kcal/mol.
我们介绍了一种新方法，可以在使用酸性部分和溶剂的密度泛函理论描述的模拟中计算离解自由能和熵值。该方法包括利用弱酸 A-COOH 到强酸 B-COOH 的化学变化，从而使得在从头算分子动力学模拟中使用化学变化自由能微扰方法成为可能。这种化学变化避免了通过用易于调节的外部有效势代替负责酸度变化的化学残基来解决总电子数和原子数变化的需要。我们的研究表明：（1）通过用屏蔽偶极子代替甲基和三氟甲基取代基，可以实现控制乙酸/三氟乙酸系列酸度变化的简单但有效的一类外部势；使用这种偶极场/量子力学（DF/QM）方法，人们可以预测气相几何形状、质子离解能、总偶极矩和水结合能，与全量子力学值吻合良好。（2）所得的化学变化微扰计算是稳定和良好收敛的，并且允许人们计算绝对 pK(a) 值，其精度主要受所采用的交换相关泛函的限制：H-COOH=2.5+/-0.6（全量子力学计算），3.7（实验）；F(3)C-COOH=0.4+/-0.6（DF/QM 计算），0.5（实验）；H(3)C-COOH=3.1+/-0.7（DF/QM 计算），4.7（实验）；（3）我们的 DF/QM 模型预测 H-COOH 和 H(3)C-COOH 之间的酸度差异主要由溶剂熵效应主导，与实验观察结果非常吻合。这些酸的离解能差的计算值 DeltaDelta(d)U=0.0+/-0.26 kcal/mol，而实验值为 0.0+/-0.1 kcal/mol。
