Klamt Andreas, Eckert Frank, Diedenhofen Michael, Beck Michael E
COSMOlogic GmbH&COKG, Burscheider Str. 515, 51381 Leverkusen, Germany.
Bayer Cropscience, BCS-R-SCLA, Alfred-Nobel-Str. 50, 40789 Monheim, Germany.
J Phys Chem A. 2003 Nov 6;107(44):9380-6. doi: 10.1021/jp034688o.
The COSMO-RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for more realistic solvation (RS) simulations, has been used for the direct prediction of pKa constants of a large variety of 64 organic and inorganic acids. A highly significant correlation of r(2) = 0.984 with a standard deviation of only 0.49 between the calculated values of the free energies of dissociation and the experimental pKa values was found, without any special adjustment of the method. Thus, we have a theoretical a priori prediction method for pKa, which has the regression constant and the slope as only adjusted parameters. Such a method can be of great value in many areas of physical chemistry, especially in pharmaceutical and agrochemical industry. To our surprise, the slope of pKa vs ΔGdiss is only 58% of the theoretically expected value of 1/RTln(10). A careful analysis with respect to different contributions as well as a comparison with the work of other authors excludes the possibility that the discrepancy is due to weaknesses of the calculation method. Hence, we must conclude that the experimental pKa scale depends differently on the free energy of dissociation than generally assumed.
COSMO-RS方法是量子化学介电连续介质溶剂化模型COSMO与用于更实际溶剂化（RS）模拟的统计热力学处理的结合，已被用于直接预测64种多种有机和无机酸的pKa常数。在解离自由能的计算值与实验pKa值之间发现了高度显著的相关性，r(2) = 0.984，标准差仅为0.49，且无需对该方法进行任何特殊调整。因此，我们有了一种用于pKa的理论先验预测方法，该方法仅将回归常数和斜率作为调整参数。这种方法在物理化学的许多领域可能具有很大价值，尤其是在制药和农用化学工业中。令我们惊讶的是，pKa与ΔGdiss的斜率仅为理论预期值1/RTln(10)的58%。对不同贡献的仔细分析以及与其他作者工作的比较排除了差异是由于计算方法缺陷的可能性。因此，我们必须得出结论，实验pKa标度对解离自由能的依赖方式与通常假设的不同。
