Do sulfonamides interact with aromatic rings?

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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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
JournalChemistry: A European Journal
Volume27
Issue number18
Pages (from-to)5721-5729
ISSN0947-6539
DOIs
Publication statusPublished - 26. Mar 2021

Keywords

  • Hydrogen Bonding
  • Models, Molecular
  • Proteins
  • Protons
  • Sulfonamides

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