Laser desorption single-conformation UV and IR spectroscopy of the sulfonamide drug sulfanilamide, the sulfanilamide-water complex, and the sulfanilamide dimer

We have studied the conformational preferences of the sulfonamide drug sulfanilamide, its dimer, and its monohydrated complex through laser desorption single-conformation UV and IR spectroscopy in a molecular beam. Based on potential energy curves for the inversion of the anilinic and the sulfonamide NH2 groups calculated at DFT level, we suggest that the zero-point level wave function of the sulfanilamide monomer is appreciably delocalized over all four conformer wells. The sulfanilamide dimer, and the monohydrated complex each exhibit a single isomer in the molecular beam. The isomeric structures of the sulfanilamide dimer and the monohydrated sulfanilamide complex were assigned based on their conformer-specific IR spectra in the NH and OH stretch region. Quantum Theory of Atoms in Molecules (QTAIM) analysis of the calculated electron density in the water complex suggests that the water molecule is bound side-on in a hydrogen bonding pocket, donating one O-H center dot center dot center dot O=S hydrogen bond and accepting two hydrogen bonds, a NH center dot center dot center dot O and a CH center dot center dot center dot O hydrogen bond. QTAIM analysis of the dimer electron density suggests that the C-i symmetry dimer structure exhibits two dominating N-H center dot center dot center dot O=S hydrogen bonds, and three weaker types of interactions: two CH center dot center dot center dot O bonds, two CH center dot center dot center dot N bonds, and a chalcogen O center dot center dot center dot O interaction. Most interestingly, the molecular beam dimer structure closely resembles the R-2(2) dimer unit-the dimer unit with the greatest interaction energy-of the alpha, gamma, and delta crystal polymorphs. Interacting Quantum Atoms analysis provides evidence that the total intermolecular interaction in the dimer is dominated by the short-range exchange-correlation contribution.