How to Predict the pKa of Any Compound in Any Solvent

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Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2022-05-24

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en

Pages

17369–17383

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ACS Omega, Volume 7, issue 20

Abstract

Acid-base properties of molecules in nonaqueous solvents are of critical importance for almost all areas of chemistry. Despite this very high relevance, our knowledge is still mostly limited to the pKa of rather few compounds in the most common solvents, and a simple yet truly general computational procedure to predict pKa's of any compound in any solvent is still missing. In this contribution, we describe such a procedure. Our method requires only the experimental pKa of a reference compound in water and a few standard quantum-chemical calculations. This method is tested through computing the proton solvation energy in 39 solvents and by comparing the pKa of 142 simple compounds in 12 solvents. Our computations indicate that the method to compute the proton solvation energy is robust with respect to the detailed computational setup and the construction of the solvation model. The unscaled pKa's computed using an implicit solvation model on the other hand differ significantly from the experimental data. These differences are partly associated with the poor quality of the experimental data and the well-known shortcomings of implicit solvation models. General linear scaling relationships to correct this error are suggested for protic and aprotic media. Using these relationships, the deviations between experiment and computations drop to a level comparable to that observed in water, which highlights the efficiency of our method.

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Publisher Copyright: © 2022 The Authors. Published by American Chemical Society.

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Busch, M, Ahlberg, E, Ahlberg, E & Laasonen, K 2022, ' How to Predict the p K a  of Any Compound in Any Solvent ', ACS Omega, vol. 7, no. 20, pp. 17369–17383 . https://doi.org/10.1021/acsomega.2c01393