Do Sulfonamides Interact with Aromatic Rings?

Jie Jian, Roel Hammink, Christine J. McKenzie, F. Matthias Bickelhaupt, Jordi Poater, Jasmin Mecinović*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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Abstract

Aromatic rings form energetically favorable interactions with many polar groups in chemical and biological systems. Recent molecular studies have shown that sulfonamides can chelate metal ions and form hydrogen bonds, however, it is presently not established whether the polar sulfonamide functionality also interacts with aromatic rings. Here, synthetic, spectroscopic, structural, and quantum chemical analyses on 2,6-diarylbenzenesulfonamides are reported, in which two flanking aromatic rings are positioned close to the central sulfonamide moiety. Fine-tuning the aromatic character by substituents on the flanking rings leads to linear trends in acidity and proton affinity of sulfonamides. This physical-organic chemistry study demonstrates that aromatic rings have a capacity to stabilize sulfonamides via through-space NH–π interactions. These results have implications in rational drug design targeting electron-rich aromatic rings in proteins.

Original languageEnglish
Pages (from-to)5721-5729
Number of pages9
JournalChemistry - A European Journal
Volume27
Issue number18
Early online date30 Dec 2020
DOIs
Publication statusPublished - 26 Mar 2021

Bibliographical note

Funding Information:
J.J. thanks the financial support from the China Scholarship Council (CSC201808440511). F.M.B. acknowledges the Netherlands Organization for Scientific Research (NWO) for financial support. J.P. thanks the Spanish MINECO (PID2019-106830GB-I00 and MDM-2017-0767) and the Generalitat de Catalunya (2017SGR348). The Carlsberg Foundation is acknowledged for funding for the X-ray diffractometer (grant CF15-0675).

Publisher Copyright:
© 2020 Wiley-VCH GmbH

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • aromatic compounds
  • molecular recognition
  • noncovalent interactions
  • polar–pi interactions
  • sulfonamides

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