Encapsulation of Cation in Sulphate and Anion in Methyl Sulphate Salt of Sulphathiazole

Abstract

The structural studies and solution studies were performed to establish the structural identity of the self-assemblies of the sulphate and methyl sulphate salt of sulphathiazole. The methyl sulphate salt was formed in situ by reaction of sulphuric acid with methanol in the presence of sulphathiazole, while a similar reaction in dimethylformamide and methanol provided the sulphate salt. The sulphate salt had two cations per anion, out of which one set formed non-covalently linked dimers. In the lattice, the dimers were encapsulated by hydrogen-bonded cyclic units that were formed by cations and anions. Whereas the methyl sulphates have the anions encapsulated within the spaces formed by hydrogen-bonded cations. An increase in solubility of the salts in ethanol compared to the parent compound was observed, and the relative solubility trend was sulphathiazole < sulphate salt < methyl sulphate salt. DFT calculations for geometry optimisation and to determine energies of optimised structures of different assemblies were performed using 6-311G+(d,p) and further with the def2QZV basis set with the M062X functional. The relative gain in energy to form mono-deprotonated salt or di-deprotonated salts was calculated. From such calculations, it was also found that the hydrate sulphate salts had higher stability over their respective anhydrous forms.