A Theoretical Structural Study of Isoniazid Complexes with Thiotriazoline

作者：Zubatyuk R I^*; Kucherenko L I; Mazur I A; Khromyleva O V; Shishkin O V

来源：Chemistry of Heterocyclic Compounds, 2014, 50(3): 438-443.

DOI：10.1007/s10593-014-1493-4

• isoniazid
• thiotriazoline
• conformational search
• molecular complexes
• quantum-chemical calculations

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 (Delta G(298) = -13.6 kcal/mol) and in aqueous solution (Delta G(298) = -7.6 kcal/mol). The formation of two-component complexes between isoniazid and MTTA without involving morpholine is considerably less favored (Delta G(298) = -6.6 kcal/mol in the gas phase and Delta G(298) = -2.6 kcal/mol in solution). Thus, morpholine may be considered as a component facilitating the formation of isoniazid complexes with MTTA.

• 出版日期2014-6