Conformational Landscape, Photochemistry, and Infrared Spectra of Sulfanilamide

Abstract

A combined matrix isolation FTIR and theoretical DFT(B3LYP)/6-311++G(3df,3pd) study of sulfanilamide (SA) was performed. The full conformational search on the potential energy surface of the compound allowed the identification of four different minima, all of them bearing the sulfamide nitrogen atom placed in the perpendicular orientation relatively to the aromatic ring and differing from each other in the orientation of the hydrogen atoms connected to the two nitrogen atoms of the molecule. All conformers were predicted to be significantly populated in the gas phase (at 100 °C, their relative populations were estimated as being 1:0.9:0.3:0.2). However, in agreement with the theoretically calculated low-energy barriers for conformational isomerization, in the low-temperature matrices, only the most stable conformer could be observed, with the remaining forms being converted into this form during matrix deposition (conformational cooling). The unimolecular photochemistry of matrix-isolated SA (in both argon and xenon) was also investigated. Upon broadband UV irradiation (λ > 215 nm), two photofragmentation pathways were observed: the prevalent pathway (A), leading to extrusion of sulfur dioxide and simultaneous formation of benzene-1,4-diamine, which then converts to 2,5-cyclohexadiene-1,4-diimine, and the minor pathway (B), conducting an γ-cleavage plus [1,3] H-atom migration from the sulfamide group to the aromatic ring, which leads to formation of iminosulfane dioxide and aniline, the latter undergoing subsequent phototransformation into cyclohexa-2,5-dien-1-imine. Finally, the crystalline polymorph of SA resulting from warming (265 K) the amorphous solid obtained from fast cooling of the vapor of the compound onto the cold (13 K) substrate of the cryostat was identified spectroscopically, and found to be the γ-crystalline phase, the one exhibiting in average longer H-bonds and an infrared spectrum resembling more that of the low temperature SA glass. Full assignment of the infrared spectra of this crystalline variety as well as of those of the β-polymorph room temperature crystalline sample and low temperature amorphous state was undertaken with help of theoretical results obtained for the crystallographically relevant dimer of SA.

Synthesis, Structure, and Cytotoxicity of a New Sulphanyl‐Bridged Thiadiazolyl‐Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction

“…On the other hand, preliminary calculations performed with the smaller 6–311++G(d,p) basis set were found to strongly underestimate the frequencies for the modes localized in the ‐SO 2 ‐ fragment, in particular the two stretching vibrations and the scissoring and wagging modes. These results follow the trends described in previous studies in which the infrared spectra of other molecules bearing the ‐SO 2 ‐ moiety were discussed. It has been shown that the use of highly polarized basis sets is necessary to provide the wavefunction the required flexibility to account properly for properties (including vibrational frequencies) of hypervalent sulphur containing molecules.…”

Synthesis, Anticancer Activity and Computational SAR Analysis of Acylsulfonylpiperazines Derivatives

“…Importantly, if we consider the position of the sulphur bound oxygen atoms with respect to the piperazine nitrogen substituents, family I and IV present the anti and the fully eclipsed conformations, respectively ( Figure 3B). Thus, in agreement with previously reported results on benzosulfonamide derivatives [35][36][37] the two most favoured families of conformers are I and IV, with family I (i.e., anti conformation of the oxygen atoms with respect to the piperazine nitrogen substituents) representing the GM family, as found in the crystal structure of N,N-dimethyltoluene-p-sulfonamide [38].…”

Preferred protonation site of a series of sulfa drugs in the gas phase revealed by IR spectroscopy

“…Originally, protonation and deprotonation sites in sulfanilamide were derived from UV spectra under acidic and basic conditions, as well as from an analysis of the possible resonance 0123456789(). : V,-vol structures and their influence on frequency and integrated absorbance of the UV bands [20][21][22]. Later also pH-dependent Raman spectra were reported [23].…”