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 para-toluensulfonamide and ortho-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 14N atom was analyzed, and this provided crucial information
for the unambiguous identification of the observed conformation of all molecules. In addition, for
ortho-toluensulfonamide, the vibration–rotation hyperfine structure related to the methyl torsion was
analyzed, and the methyl group rotation barrier was determined. For benzensulfonamide, partial rS
and r0 structures were established from the experimental rotational constants of the parent and two
deuterated isotopic species. In all compounds except ortho-toluensulfonamide, the amino group of
the sulfonamide group lies perpendicular to the benzene plane with the aminic hydrogens eclipsing
the oxygen atoms. In ortho-toluensulfonamide, where weak attractive interactions occur between
the nitrogen lone pair and the methyl hydrogen atoms, the amino group lies in a gauche orientation,
retaining the eclipsed configuration with respect to the SO2 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.