Multinuclear NMR and vibrational spectroscopy studies of the substituent effects in benzensulphonamide inhibitors of the enzyme carbonic anhydrase

Abstract

Substituent effects on the electronic structure of sixteen biologically active benzensulphonamide derivatives were investigated by means of 15N, 13C, 1H NMR, and IR spectroscopy, as well as by quantum chemical calculations. Good correlations were found between the spectroscopic data and both substituent constant and computed electronic charges. On this basis the substituent effects are interpreted in terms of electronic charge perturbation, which is linearly transmitted from the substituent to the biofunctional −SO 2NH 2 group. The resonance nature of the substituent seems most important in determining the 15N chemical shifts, which follow a “reverse” trend; i.e., electron-donor substituents induce downfield 15N shifts.