pKa prediction in non-aqueous solvents
Name
J Comput Chem - 2024 - Zheng - pKa prediction in non‐aqueous solvents.pdf
Description
Published version
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2.06 MB
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Adobe PDF
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Author(s)
Zheng, Jonathan W
Al Ibrahim, Emad
Kaljurand, Ivari
Leito, Ivo
Green, William H
Date Issued
December 11, 2024
Journal
Journal of Computational Chemistry
Publisher
Wiley
Citation
Zheng, Jonathan W, Al Ibrahim, Emad, Kaljurand, Ivari, Leito, Ivo and Green, William H. 2024. "pKa prediction in non-aqueous solvents." Journal of Computational Chemistry, 46 (1).
Version
Final published version
Abstract
Acid dissociation constants (pKa ) are widely measured and studied, most typically inwater. Comparatively few datasets and models for non-aqueous pKa values exist. Inthis work, we demonstrate how the pKa in one solvent can be accurately determinedusing reference data in another solvent, corrected by solvation energy calculationsfrom the COSMO-RS method. We benchmark this approach in 10 different solvents,and find that pKa values calculated in six solvents deviate from experimental data onaverage by less than 1 pKa unit. We observe comparable performance on a morediverse test set including amino acids and drug molecules, with higher error for largemolecules. The model performance in four other solvents is worse, with one MAEexceeding 3 pKa units; we discuss how such errors arise due to both model error andinconsistency in obtaining experimental data. Finally, we demonstrate how this tech-nique can be used to estimate the proton transfer energy between different solvents,and use this to report a value of the proton's solvation energy in formamide, a quan-tity that does not have a consensus value in literature.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1002/jcc.27517
