Structure, acidity and basicity of a benzene disulfonamide inhibitor of carbonic anhydrase

N-(4-Diethylaminoethoxybenzyl)benzene-1,4-bis(sulfonamide) (I-3) and its hydrochloride salt (I-3·HCl) were prepared. The X-ray molecular structure of (I-3·HCl) has been determined. The gas phase geometry of free base, its anion, cation and hydrochloride has been computed using Becke3LYP/6-311++G(d,p) and B97D/6-311++G(d,p) model chemistry. The conformational behavior of these systems in water was examined using the solvation CPCM model. In the solid state this compound possesses a sandwich-like structure. According to the density functional calculations using B97D Grimme’s functional including dispersion this structure is also present in the gas phase and/or in water solution. On the other hand, the B3LYP functional calculations prefer extended conformer in gas phase. The calculated gas-phase acidity and basicity are conformationally dependent and low, indicating that I-3 behaves as a weak acid and/or base.