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Do Sulfonamides Interact with Aromatic Rings?
Author(s) -
Jian Jie,
Hammink Roel,
McKenzie Christine J.,
Bickelhaupt F. Matthias,
Poater Jordi,
Mecinović Jasmin
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202004732
Subject(s) - aromaticity , moiety , chemistry , sulfonamide , hydrogen bond , aromatic amino acids , ring (chemistry) , stereochemistry , combinatorial chemistry , computational chemistry , molecule , organic chemistry , enzyme
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.