Do Sulfonamides Interact with Aromatic Rings?

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-pi interactions. These results have implications in rational drug design targeting electron-rich aromatic rings in proteins.

Automated summary

This study investigates the interactions between sulfonamides and aromatic rings by analyzing 2,6-diarylbenzenesulfonamides, and shows that fine-tuning the aromatic character with substituents can linearly affect the acidity and proton affinity of sulfonamides. The study demonstrates that aromatic rings have the capacity to stabilize sulfonamides through through-space NH-pi interactions, which has implications for rational drug design targeting electron-rich aromatic rings in proteins.