Estimation of empirically fitted parameters for calculating pK a values of thiols in a fast and reliable way


Two empirically fitted parameters (m and C 0) for the calculation of pK a values for thiols are provided for the first time, at 74 levels of theory. The coefficients were obtained by least-squares fits of the difference in Gibbs energy between each acid and its conjugated base versus experimental pK a values. The reliability of this fitted parameters approach (FPA) was confirmed using an independent test set of molecules. It was found that deviations from experiments are systematically lower than 0.5 pK a units, in terms of mean unsigned errors. In addition, all the tested levels of theory produced maximum absolute errors lower than 1 pK a unit. The parameters estimated here are expected to facilitate pK a calculations, using electronic structure-based strategies, with uncertainties close to the experimental ones. Albeit the present study deals only with molecules of modest complexity, i.e., the reliability of the FPA for more complex systems remains to be tested, it seems to be a promising approach for obtaining pK a values of thiols in a fast and reliable way.

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We gratefully acknowledge the Laboratorio de Visualización y Cómputo Paralelo at Universidad Autónoma Metropolitana-Iztapalapa and the Dirección General de Servicios de Cómputo Académico (DGTIC) at Universidad Nacional Autónoma de México. Adriana Pérez-González acknowledges the economic support of the Program of Cátedras - CONACYT from CONACyT - UAMI (2015–2025). Romina Castañeda-Arriaga acknowledges the economic support of the program of Estancias Posdoctorales Nacionales from CONACYT.

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Correspondence to Juan Raúl Alvarez-Idaboy or Annia Galano.

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Published as part of the special collection of articles “In Memoriam of Claudio Zicovich”.

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Pérez-González, A., Castañeda-Arriaga, R., Verastegui, B. et al. Estimation of empirically fitted parameters for calculating pK a values of thiols in a fast and reliable way. Theor Chem Acc 137, 5 (2018).

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  • Acid constant
  • Deprotonation
  • Density functional theory
  • Acid–base equilibria