A Theoretical Structural Study of Isoniazid Complexes with Thiotriazoline

Abstract

A combined molecular mechanics and quantum chemistry modeling was performed for investigation of the structure and relavive stability of two- and three-component complexes formed by the antituberculosis agent isoniazid with morpholinium (3-methyl-1,2,4-triazol-5-yl)thioacetate (MTTA). The possible interactions between the molecules were identified by molecular mechanics calculations, and the stability of the complexes was calculated by the density functional method B97-D/6-311G**, with accounting for the solvent effects in the SMD continuum model. The calculations showed that stable complexes of isoniazid with this thiatriazoline are possible both in the gas phase (ΔG298 = -13.6 kcal/mol) and in aqueous solution (ΔG298 = -7.6 kcal/mol). The formation of two-component complexes between isoniazid and MTTA without involving morpholine is considerably less favored (ΔG298 = -6.6 kcal/mol in the gas phase and ΔG298 = -2.6 kcal/mol in solution). Thus, morpholine may be considered as a component facilitating the formation of isoniazid complexes with MTTA.