Ho Junming
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
Phys Chem Chem Phys. 2015 Jan 28;17(4):2859-68. doi: 10.1039/c4cp04538f. Epub 2014 Dec 15.
Continuum solvent calculations of pKas and reduction potentials usually entail the use of a thermodynamic cycle to express the reaction free energy in terms of gas phase energies and free energies of solvation. In this work, we present a systematic study comparing the solution phase free energy changes obtained in this manner with those directly computed within the SMD solvation model against a large test set of 117 pKas and 42 reduction potentials in water and DMSO. The inclusion of vibrational contributions in the free energy of solvation has a negligible impact on the accuracy of thermodynamic cycle predictions of pKas and reduction potentials. Additionally, when gas phase energies in the thermodynamic cycle are computed at more accurate levels of theory, very similar results (mean unsigned difference of 0.5 kcal mol(-1)) can be achieved when the high-level computations (MP2/GTMP2Large and G3(MP2)-RAD(+)) are directly carried out within the continuum model. Increasing the accuracy of the electronic structure theory may or may not improve the agreement with experiment suggesting that the error is largely in the solvation model. For amino acids where their gas and solution phase species exist as different tautomers, the direct approach provided a significant improvement in calculated pKas. These results demonstrate that direct calculation of solution phase pKas and reduction potentials within the SMD model provides a general and reliable approximation to corresponding thermodynamic cycle based protocols, and is recommended for systems where solvation induced changes in geometry are significant. Further studies are necessary to ascertain whether the results are generalisable to other continuum solvation models.
pKa值和还原电位的连续介质溶剂计算通常需要使用热力学循环，以便根据气相能量和溶剂化自由能来表示反应自由能。在这项工作中，我们进行了一项系统研究，将以这种方式获得的溶液相自由能变化与在SMD溶剂化模型中直接计算得到的结果进行比较，所针对的是包含117个pKa值和42个在水和二甲基亚砜中的还原电位的大型测试集。在溶剂化自由能中包含振动贡献对pKa值和还原电位的热力学循环预测精度的影响可忽略不计。此外，当在更精确的理论水平上计算热力学循环中的气相能量时，在连续介质模型中直接进行高水平计算（MP2/GTMP2Large和G3(MP2)-RAD(+)）时，可以得到非常相似的结果（平均无符号差值为0.5 kcal mol⁻¹）。提高电子结构理论的精度可能会也可能不会改善与实验的一致性，这表明误差主要存在于溶剂化模型中。对于其气相和溶液相物种以不同互变异构体形式存在的氨基酸，直接方法在计算的pKa值方面有显著改进。这些结果表明，在SMD模型中直接计算溶液相pKa值和还原电位为基于相应热力学循环的方法提供了一种通用且可靠的近似方法，并且推荐用于溶剂化引起的几何结构变化显著的系统。有必要进行进一步研究以确定这些结果是否可推广到其他连续介质溶剂化模型。
