Quantum chemical predictions of aqueous pKa values for OH groups of some α-hydroxycarboxylic acids based on ab initio and DFT calculations

Abstract

Determination of pKa values, especially for OH groups of α-hydroxycarboxylic acids, is challenging and rarely reported. Here, successive pKa values for COOH, and more importantly for OH groups of the nine biologically important α-hydroxycarboxylic acids (glycolic, lactic, methyl lactic, α-hydroxybutyric, mandelic, atrolactic, benzilic, malic, and citramalic) were calculated computationally. We benchmarked the accuracy for predicting pKa values by HF, MP2, B3LYP, B97D, B2PLYP, M06-2X, G3 and CBS-QB3 levels of theory combined with CPCM and SMD solvation models applied to lactic acid whose experimental pKa values are reported in the literature. Also, we considered six thermodynamic cycles in combination with a number of DFT methods and some cavity sets, such as, UAKS, Pauling and Bondi to obtain the reasonable results. Finally, we employed two best methods to predict the pKa values of the remaining eight α-hydroxycarboxylic acids. Estimated pKa values of OH groups are reported for these α–hydroxycarboxylic acids that were not yet determined experimentally.