Widespread misinterpretation of pKa terminology for zwitterionic compounds and its consequences
Name
2024_pKa_inconsistency.pdf
Size
673.35 KB
Format
Adobe PDF
Checksum (MD5)
0939fdf929893d39f57b7f4d78ec4ad2
Author(s)
Zheng, Jonathan
Leito, Ivo
Green, William
Date Issued
November 19, 2024
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Citation
Widespread Misinterpretation of pKa Terminology for Zwitterionic Compounds and Its Consequences. Jonathan W. Zheng, Ivo Leito, and William H. Green. Journal of Chemical Information and Modeling 2024 64 (23), 8838-8847.
Version
Author's final manuscript
Abstract
The acid dissociation constant (pKa), which quantifies the propensity for a solute to donate a proton to its solvent, is crucial for drug design and synthesis, environmental fate studies, chemical manufacturing, and many other fields. Unfortunately, the terminology used for describing acid-base phenomena is inconsistent, causing large potential for misinterpretation. In this work, we examine a systematic confusion underlying the definition of "acidic" and "basic" pKa values for zwitterionic compounds. Due to this confusion, some pKa data is misrepresented in data repositories, including the widelyused and highly trusted ChEMBL Database. Such datasets are widely used to supply training data for pKa prediction models, and hence, confusion and errors in the data makes model performance worse. Herein, we discuss the intricacies of this issue. We make suggestions for describing acid-base phenomena, training pKa prediction models, and stewarding pKa datasets, given the high potential for confusion and potentially high impact of accurately describing acid-base phenomena.
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/acs.jcim.4c01420
