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

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journal contribution
posted on 14.01.2010, 00:00 by Shuming Zhang, Jon Baker, Peter Pulay
In part 1 of this series, we developed a protocol for the large-scale calculation of pKa 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, pKa values are calculated from a linear regression fit to deprotonation energies: pKa(f) = αf(EAEHA) + βf, where f denotes a family of functional groups. In this paper, we derive (αf, βf) values for the acidic functional groups −COOH, −POOH, alcoholic and phenolic −OH, −SH, −NHOH/NOH, and −NROH, using a data set of 449 experimental pKa 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 pKa units or less for each with a maximum error range of ±1.5 pKa units. In certain subgroups, such as monocarboxylic acids, considerably better fits (mean absolute deviation ∼0.20 pKs units) were obtained at the cost of more empirical parameters. Almost 70% of pKa’s calculated by our protocol lie within ±0.4 pKa units and over 90% within ±0.8 pKa units of the experimental reference value. Our results compare favorably with previous similar models which have greater computational cost.