Ligand-controlled Ru(III)-catalyzed oxidation of Isoniazid by chloramine-T in acidic medium: a kinetic and mechanistic investigation

This study investigates the kinetics and intricate reaction mechanism of the homogeneous Ru(III)-catalyzed oxidation of the anti-tubercular drug Isoniazid by chloramine-T in an acidic medium, within the temperature range of 30–45 °C. The experiments were performed under well-defined and comparable solution conditions, with acidity controlled through the initial concentration of perchloric acid. Mercuric acetate was employed as a chloride-ion scavenger. Kinetic analysis revealed that the reaction is first order with respect to both Ru(III) and isoniazid under pseudo-first-order conditions. The reaction exhibited an unusual zero-order dependence on chloramine-T and was found to proceed through an inner-sphere mechanism involving a proposed Ru(IV)–isoniazid intermediate, distinguishing it from previously reported oxidation systems. The reaction rate increased with increasing [H⁺], whereas the chloride ions inhibited the reaction. The influence of imidazole as an auxiliary ligand was also examined. Initial inhibition was observed due to coordination of imidazole with Ru(III), followed by restoration of catalytic activity at higher imidazole concentrations through the formation of a more labile Ru–imidazole complex. The temperature dependence of the reaction rate was also assessed through kinetic measurements at different temperatures, enabling evaluation of activation parameters. The oxidation product was characterized by mass spectrometry and UV–Vis spectroscopy, and its formation was monitored spectrophotometrically to determine the reaction stoichiometry. Based on kinetic results, a plausible mechanism involving the formation of a Ru–Isoniazid complex has been proposed, and the corresponding rate law has been derived. This study establishes a ligand- and speciation-controlled Ru(III)-catalyzed oxidation pathway for isoniazid that differs significantly from previously reported direct oxidation mechanisms.