Comparison of different atomic charge schemes for predicting pKa variations in substituted anilines and phenols

A number of different methods have been proposed for assigning partial charges to the atoms of a molecule, including both quantum chemical and empirical schemes. A reasonable expectation for any successful calculational scheme is that the atomic charges it produces should vary in a manner consistent with chemical intuition and, more specifically, that these variations should be correlated in a sensible way with experimental observations. Seven of the most popular atomic charge schemes (Bader's AIM charges Q(AIM), electrostatic potential charges Q(ESP), GAPT charges Q(GAPT), Gasteiger pi charges Q(Gast), Lowdin charges Q(Low), Mulliken charges Q(Mul), and charges derived from natural population analysis Q(NPA)) were tested for their ability to represent variations in the pK(a)'s Of 19 monosubstituted anilines and 19 monosubstituted phenols. In most cases the calculations were performed at the B3LYP/6-311G** level of theory. For the substituted anilines, the amino nitrogen, anilinium proton, and total amino group charges were taken as representative regression parameters, and for the phenols, the phenolic hydrogen, phenoxide oxygen, and hydroxyl group charges were employed. Overall, Q(AIM), Q(Low), and Q(NPA) yielded the most successful correlations with the pKa's of these compounds, although for the phenol series, Q(GAPT) and Q(Mul) also yielded good results. (C) 2002 Wiley Periodicals, Inc.