title: pKa prediction from an ab initio bond length: part 3--benzoic acids and anilines.
abstract: 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.
authors.affiliation: Manchester Interdisciplinary Biocentre (MIB), Manchester, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Harding
authors.forename: P L A
authors.initials: PL
authors.lastname: Popelier
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D001565:Benzoates / Q000737:chemistry*; D005740:Gases / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D062385:Hydroxybenzoates / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical
chemical_list: D000814:Aniline Compounds; D001565:Benzoates; D005740:Gases; D062385:Hydroxybenzoates; D006859:Hydrogen; C023650:aniline