Journal of Molecular Modeling

, 25:354 | Cite as

Correlation between the pKa and nuclear shielding of α-hydrogen of ketones

  • Suting Xing
  • Juanfeng Lu
  • Xinyun Zhao
  • Xi ChenEmail author
  • Chang-Guo ZhanEmail author
Original Paper


The α-H acidity is an important chemical property of ketones that has attracted much research interest. Theoretical prediction of pKa for ketone α-H is significant. In this work, we theoretically studied the nuclear shielding of various α-Hs in a set of ketones and that of the corresponding enolic hydroxyl Hs in tautomeric enol forms. It has been demonstrated through linear regression analyses that the pKa values of these ketones correlate with both sets of the calculated nuclear shielding values. The correlation coefficient R2 of the linear correlation relationship is 0.90. The present work has provided a new approach to computationally evaluating the acidity of α-Hs in ketones, enabling us to semi-empirically predict the ketone α-H acidity from the calculated nuclear shielding values.

Graphical Abstract

Experimental pKa values in DMSO vs predicted pKa values calculated from 1H nuclear shielding for the hydroxyl hydrogens in the enol forms and for the α-Hs in the keto forms. The surrounding solvent effects were modelled by keto/enol-DMSO clusters and SMD solvent models


Nuclear shielding pKa Ketone Enol Linear correlation 


Funding information

The work was supported by the National Natural Science Foundation of China (grant number 21273089), the Fundamental Research Funds for the South-Central University for Nationalities (CZW17004), the Open Project Fund of the Key Laboratory of the Pesticides and Chemical Biology of Central China Normal University (grant number 2018-A01).

Supplementary material

894_2019_4244_MOESM1_ESM.docx (5 mb)
ESM 1(DOCX 5164 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Chemistry & Materials ScienceSouth-Central University for NationalitiesWuhanPeople’s Republic of China
  2. 2.Department of Pharmaceutical Sciences, College of PharmacyUniversity of KentuckyLexingtonUSA

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