A Reliable and Efficient First Principles-Based Method for Predicting pK(a) Values. 2. Organic Acids

by Zhang, Shuming; Baker, Jon; Pulay, Peter

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/=NOH, 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 similar to 0.20 pK(a) 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.

Journal of Physical Chemistry A
Start Page
1520-5215; 1089-5639