The Shapes of Sulfonamides: A Rotational Spectroscopy Study.

Benzenesulfonamides are a class of molecules of extreme interest in the biochemical field because many of them are active against a variety of diseases. In this work, the pharmacophoric group benzensulfonamide, its derivatives toluensulfonamide and toluensulfonamide, and the bioactive molecule sulfanilamide, were investigated using rotational spectroscopy to determine their conformations and the influence of different substituents on their structures. For all species, the hyperfine structure due to the N atom was analyzed, and this provided crucial information for the unambiguous identification of the observed conformation of all molecules. In addition, for -toluensulfonamide, the vibration-rotation hyperfine structure related to the methyl torsion was analyzed, and the methyl group rotation barrier was determined. For benzensulfonamide, partial and structures were established from the experimental rotational constants of the parent and two deuterated isotopic species. In all compounds except -toluensulfonamide, the amino group of the sulfonamide group lies perpendicular to the benzene plane with the aminic hydrogens eclipsing the oxygen atoms. In -toluensulfonamide, where weak attractive interactions occur between the nitrogen lone pair and the methyl hydrogen atoms, the amino group lies in a orientation, retaining the eclipsed configuration with respect to the SO frame. A comparison of the geometrical arrangements found in the PDB database allowed us to understand that the bioactive conformations are different from those found in isolated conditions. The conformations within the receptor are reached with an energy cost, which is balanced by the interactions established in the receptor.