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Isodesmic reaction for pK a calculations of common organic molecules

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Abstract

Three quantum chemistry methods (B3LYP, M05-2X and CBS-4B3*) have been used, in combination with SMD and CPCM continuum solvent models, to calculate the aqueous pK a values of common organic compounds (aliphatic alcohols, carboxylic acids, amines, phenols, benzoic acids and pyridines) by using an isodesmic reaction. Good precision is found for all the studied functional groups, resulting mean absolute deviations of 0.5–1 pK a units (equivalent to the best results obtained with thermodynamic cycles). It is worthy to note that no explicit water molecules were needed with the isodesmic reaction. In addition, the quality of the results is not strongly dependent on the combination of quantum chemistry method, solvent model and reference species. Therefore, the isodesmic reaction could be successfully used when dealing with gas-phase unstable species, with species that undergo large conformational changes between gas-phase and solution-phase or other difficult cases for the thermodynamic cycles.

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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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  1. Institut d’Investigació en Ciènces de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, 07122, Palma de Mallorca, Spain

    Sebastián Sastre, Rodrigo Casasnovas, Francisco Muñoz & Juan Frau

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  1. Sebastián Sastre
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  2. Rodrigo Casasnovas
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  3. Francisco Muñoz
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  4. Juan Frau
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Correspondence to Juan Frau.

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Published as part of the special collection of articles derived from the 8th Congress on Electronic Structure: Principles and Applications (ESPA 2012).

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Sastre, S., Casasnovas, R., Muñoz, F. et al. Isodesmic reaction for pK a calculations of common organic molecules. Theor Chem Acc 132, 1310 (2013). https://doi.org/10.1007/s00214-012-1310-z

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