Metal-catalysed auto-oxidation of isoniazid

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Abstract
Mn++ and Cu++ were the most active catalysts found for isoniazid auto-oxidation at pH 7.5 and 37[degree]. The velocity constant of the oxidation of 0.2 m[image] isoniazid was 2.9 hr."l when catalyzed by 0.045 m[image]Mn++ in bicarbonate buffer, and 3.4 hr.l by 0.045 m[image] Cu++ in borate buffer. Mn++ was active down to 0.05 [mu][image]. The activity of the catalysts depended on the buffer. Mn++ was most active in phosphate or bicarbonate and Cu++ in bicarbonate, borate or Veronal (barbital). Certain chelating agents increased the catalytic activity of Mn++ when they were present at a lower molar concentration than it, but inhibited its activity at higher concentrations. H2O2 inhibited isoniazid auto-oxidation catalyzed by Mn++, but stimulated that catalyzed by Cu++. Isoniazid auto-oxidation followed an approximately unimoleuclar course under certain conditions. Hydrazides of a number of other acids also auto-oxidized. isoNicotinic acid, diisonicotinylhydrazine and isonicotinamide were products of auto-oxidation of isoniazid catalyzed by either metal. H2O2 resulted from auto-oxidation catalyzed by Mn++. Free radicals, probably OH and radicals derived from isoniazid, were formed during auto-oxidation catalyzed by Cu++. Peroxidase did not affect isoniazid unless H2O2 and a phenol were present, when condensation products derived from isoniazid and the phenol were formed. It is suggested that free radical formation during auto-oxidation is a major factor in the toxicity of isoniazid and other auto-oxidizable substances.