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

Determination of p K a values, especially for OH groups of α-hydroxycarboxylic acids, is challenging and rarely reported. Here, successive p K a 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 p K a 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 p K a 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 p K a values of the remaining eight α-hydroxycarboxylic acids. Estimated p K a values of OH groups are reported for these α–hydroxycarboxylic acids that were not yet determined experimentally. [ABSTRACT FROM AUTHOR]