Manchester Interdisciplinary Biocentre (MIB), Manchester, UK.
Phys Chem Chem Phys. 2011 Jun 21;13(23):11283-93. doi: 10.1039/c1cp20380k. Epub 2011 May 13.
The prediction of pK(a) from a single ab initio bond length has been extended to provide equations for benzoic acids and anilines. The HF/6-31G(d) level of theory is used for all geometry optimisations. Similarly to phenols (Part 2 of this series of publications), the meta-/para-substituted benzoic acids can be predicted from a single model constructed from one bond length. This model had an impressive RMSEP of 0.13 pK(a) units. The prediction of ortho-substituted benzoic acids required the identification of high-correlation subsets, where the compounds in the same subset have at least one of the same (e.g. halogens, hydroxy) ortho substituent. Two pK(a) equations are provided for o-halogen benzoic acids and o-hydroxybenzoic acids, where the RMSEP values are 0.19 and 0.15 pK(a) units, respectively. Interestingly, the bond length that provided the best model differed between these two high-correlation subsets. This demonstrates the importance of investigating the most predictive bond length, which is not necessarily the bond involving the acid hydrogen. Three high-correlation subsets were identified for the ortho-substituted anilines. These were o-halogen, o-nitro and o-alkyl-substituted aniline high-correlation subsets, where the RMSEP ranged from 0.23 to 0.44 pK(a) units. The RMSEP for the meta-/para-substituted aniline model was 0.54 pK(a) units. This value exceeded our threshold of 0.50 pK(a) units and was higher than both the m-/p-benzoic acids in this work and the m-/p-phenols (RMSEP = 0.43) of Part 2. Constructing two separate models for the meta- and para- substituted anilines, where RMSEP values of 0.63 and 0.33 pK(a) units were obtained respectively, revealed it was the meta-substituted anilines that caused the large RMSEP value. For unknown reasons the RMSEP value increased with the addition of a further twenty meta-substituted anilines to this model. The C-N bond always produced the best correlations with pK(a) for all the high-correlation subsets. A higher level of theory and an ammonia probe improved the statistics only marginally for the hydroxybenzoic acid high-correlation subsets.
从单个从头算键长预测 pK(a) 已扩展到为苯甲酸和苯胺提供方程式。所有几何优化均采用 HF/6-31G(d) 理论水平。与酚类（本系列出版物的第 2 部分）类似，间/对取代苯甲酸可从一个由一个键长构建的单个模型中预测。该模型的 RMSEP 令人印象深刻，为 0.13 pK(a) 单位。邻位取代苯甲酸的预测需要识别高相关子集，其中同一子集中的化合物至少具有相同的（例如卤素、羟基）邻位取代基之一。为邻卤代苯甲酸和邻羟基苯甲酸提供了两个 pK(a) 方程，其 RMSEP 值分别为 0.19 和 0.15 pK(a) 单位。有趣的是，为这两个高相关子集提供最佳模型的键长不同。这证明了研究最具预测性键长的重要性，而该键长不一定是涉及酸氢的键长。鉴定了邻位取代苯胺的三个高相关子集。它们是邻卤代、邻硝基和邻烷基取代苯胺的高相关子集，其 RMSEP 范围为 0.23 至 0.44 pK(a) 单位。间/对取代苯胺模型的 RMSEP 为 0.54 pK(a) 单位。该值超过了我们 0.50 pK(a) 单位的阈值，并且高于本工作中的间/对苯甲酸和第 2 部分的间/对苯酚（RMSEP = 0.43）。为间位和对位取代苯胺分别构建两个单独的模型，分别得到 RMSEP 值为 0.63 和 0.33 pK(a) 单位，结果表明是间位取代苯胺导致 RMSEP 值较大。由于未知原因，随着向该模型中添加另外二十个间位取代苯胺，RMSEP 值增加。对于所有高相关子集，C-N 键总是与 pK(a) 产生最佳相关性。更高水平的理论和氨探针仅略微改善了羟基苯甲酸高相关子集的统计数据。
