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 hydrogen bonds, however, it is presently not established whether the sulfonamide functionality also interacts aromatic rings. Here, synthetic, spectroscopic, structural, quantum analyses on 2,6-diarylbenzenesulfonamides are reported, which two flanking positioned close to central moiety. Fine-tuning character by substituents leads linear trends acidity proton affinity of sulfonamides. This physical-organic chemistry study demonstrates a capacity stabilize via through-space NH–? interactions. These results implications rational drug design targeting electron-rich proteins.