Accurate pKa calculations for carboxylic acids using Complete Basis Set and Gaussian-n models combined with CPCM continuum solvation methods

ACS Citation

Liptak, M. D.; Shields, G. C. Accurate pKa Calculations for Carboxylic Acids Using Complete Basis Set and Gaussian-N Models Combined with CPCM Continuum Solvation Methods. J. Am. Chem. Soc. 2001, 123 (30), 7314-€“7319.


Complete Basis Set and Gaussian-n methods were combined with CPCM continuum solvation methods to calculate pK(a) values for six carboxylic acids. An experimental value of -264.61 kcal/mol for the free energy of solvation of H+, DeltaG(s)(H+), was combined with a value for G(gas)(H+) of -6.28 kcal/mol to calculate pK(a) values with Cycle 1. The Complete Basis Set gas-phase methods used to calculate gas-phase free energies are very accurate, with mean unsigned errors of 0.3 kcal/mol and standard deviations of 0.4 kcal/mol. The CPCM solvation calculations used to calculate condensed-phase free energies are slightly less accurate than the gas-phase models, and the best method has a mean unsigned error and standard deviation of 0.4 and 0.5 kcal/mol, respectively. The use of Cycle I and the Complete Basis Set models combined with the CPCM solvation methods yielded pK(a) values accurate to less than half a pK(a) unit.

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Journal of the American Chemical Society

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