A Reliable and Efficient First Principles-Based Method for Predicting pKa Values. 2. Organic Acids

In part 1 of this series, we developed a protocol for the large-scale calculation of pK(a) values in aqueous solutions from first principles calculations, with the goal of striking a compromise between accuracy and computational efficiency. Following previous workers in the field, pK(a) values are calculated from a linear regression fit to deprotonation energies: pK(a)(f) = alpha(f)(E(A)(-) - E(HA)) + beta(f), where f denotes a family of functional groups. In this paper, we derive (alpha(f), beta(f)) values for the acidic functional groups -COOH, -POOH, alcoholic and phenolic -OH, -SH, -NHOH/ horizontal lineNOH, and -NROH, using a data set of 449 experimental pK(a) values. Several groupings of these functional groups were explored; our final recommended method uses five families (10 empirical parameters). Mean absolute deviations between our fits and experiment are 0.4 pK(a) units or less for each with a maximum error range of +/-1.5 pK(a) units. In certain subgroups, such as monocarboxylic acids, considerably better fits (mean absolute deviation approximately 0.20 pK(s) units) were obtained at the cost of more empirical parameters. Almost 70% of pK(a)'s calculated by our protocol lie within +/-0.4 pK(a) units and over 90% within +/-0.8 pK(a) units of the experimental reference value. Our results compare favorably with previous similar models which have greater computational cost.