Gas-phase acidity of sulfonamides: implications for reactivity and prodrug design

A computational study at the Density Functional Theory level was performed on bioactive and model sulfonamides with the aim of determining the factors affecting the acidity of the sulfonamido group. The effects of introducing different substituents at either the para-aryl or the N1-sulfonamide positions were independently analyzed. The implications for the design of suitable sulfonamide prodrugs are discussed.