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Avoiding gas-phase calculations in theoretical pK a predictions

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Abstract

CBS-QB3, two simplified and less computationally demanding versions of CBS-QB3, DFT-B3LYP, and HF quantum chemistry methods have been used in conjunction with the CPCM continuum solvent model to calculate the free energies of proton exchange reactions in water solution following an isodesmic reaction approach. According to our results, the precision of the predicted pK a values when compared to experiment is equivalent to that of the thermodynamic cycles that combine gas-phase and solution-phase calculations. However, in the aqueous isodesmic reaction schema, the accuracy of the results is less sensitive to the presence of explicit water molecules and to the global charges of the involved species since the free energies of solvation are not required. In addition, this procedure makes easier the prediction of pK a values for molecules that undergo large conformational changes in solvation process and makes possible the pK a prediction of unstable species in gas-phase such as some zwitterionic tautomers. The successive pK a values of few amino acids corresponding to the ionization of the α-carboxylic acid and α-amine groups, which is one of the problematic cases for thermodynamic cycles, were successfully calculated by employing the aqueous isodesmic reaction yielding mean absolute deviations of 0.22 and 0.19 pK a units for the first and second ionization processes, respectively.

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Acknowledgments

This work was funded by the Spanish Government in the framework of Project CTQ2008-02207/BQU. One of us (R. C.) wishes to acknowledge a fellowship from the Spanish MEC within the FPU program. The authors are grateful to “Centro de Cálculo de Superomputación de Galicia” (CESGA) and to “Centre de Supercomputació de Catalunya” (CESCA) for access to their computational facilities.

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Authors and Affiliations

  1. Department of Chemistry, Universitat Illes Balears, 07122, Palma de Mallorca, Spain

    Rodrigo Casasnovas, David Fernández, Joaquín Ortega-Castro, Juan Frau, Josefa Donoso & Francisco Muñoz

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  1. Rodrigo Casasnovas
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  2. David Fernández
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  3. Joaquín Ortega-Castro
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  4. Juan Frau
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  5. Josefa Donoso
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  6. Francisco Muñoz
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Correspondence to Juan Frau.

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Casasnovas, R., Fernández, D., Ortega-Castro, J. et al. Avoiding gas-phase calculations in theoretical pK a predictions. Theor Chem Acc 130, 1–13 (2011). https://doi.org/10.1007/s00214-011-0945-5

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