Kinetics of the Reaction between Cobinamide and Isoniazid in Aqueous Solutions

The kinetics and mechanism of the reaction of diaquacobinamide (Cbi(III)) with isoniazid (iso-nicotinoyl hydrazide (INH)) are studied. It is determined that the composition of the products depends on the ratio between the concentrations of the reactants. Adding excess INH to cobinamide results in the rapid formation of a stable complex of Cbi(III) with two isoniazid molecules. If the concentrations of isoniazid and cobinamide are close, or cobinamide is in excess, then a complex of Cbi(III) with one isoniazid molecule initially forms. There is then a fast inner-sphere electron transfer to yield an unstable complex of reduced Cbi(II) with hydrazyl radical (RN 2 H 2 )(Cbi(II)) that decomposes to form reduced cobinamide and the products of the oxidation of isoniazid: isonicotinamide, pyridine-4-carboxaldehyde, and isonicotinic acid (INA). It is concluded that with a 1000% excess of cobinamide, the main product of the oxidation of INH is INA.