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.

How to Cite
Zubatyuk, R. I.; Kucherenko, L. I.; Mazur, I. A.; Khromyleva, O. V.; Shishkin, O. V. Chem. Heterocycl. Compd. 2014, 50, 438. [Khim. Geterotsikl. Soedin. 2014, 476.]

For this article in the English edition see DOI 10.1007/s10593-014-1493-4