Correlations Between Quantum Chemical Indices and the pKas of a Diverse Set of Organic Phenols

In earlier studies (Gross and Seybold, Int J Quantum Chem, 2001, 85, 569; Gross et al., Int J Quantum Chem, 2002, 90, 445), it was shown that variations in several calculated quantum chemical charge and energy parameters were strongly correlated with the pKa variations in a set of substituted phenols. Here, we examine whether this approach can be extended to the pKas of a diverse set of more complex organic phenolic compounds. Three levels of theory were tested: (1) the RM1 semiempirical method, with and without the SM5.4 solvent model, (2) density functional theory at the B3LYP/6-311G** level, and (3) single-point B3LYP/6-31!G* calculations with the self-consistent reaction field SM8 solvent model. The best results were obtained with quantum chemical indices calculated using the SM8 solvent model. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem 109: 3679–3684, 2009