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 language | English |
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Pages (from-to) | 5721-5729 |
Number of pages | 9 |
Journal | Chemistry - A European Journal |
Volume | 27 |
Issue number | 18 |
Early online date | 30 Dec 2020 |
DOIs | |
Publication status | Published - 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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CCDC 2030936: Experimental Crystal Structure Determination
Jian, J. (Contributor), Hammink, R. (Contributor), McKenzie, C. J. (Contributor), Bickelhaupt, F. M. (Contributor), Poater, J. (Contributor) & Mecinović, J. (Contributor), Unknown Publisher, 1 Jan 2021
DOI: 10.5517/ccdc.csd.cc265c2v, https://doi.org/10.5517%2Fccdc.csd.cc265c2v
Dataset / Software: Dataset