Is the isonicotinoyl radical generated during activation of isoniazid by MnIII-pyrophosphate?

The antituberculosis drug isoniazid (INH) is quickly oxidised by stoichiometric amounts of manganese(III)-pyrophosphate and the following products were identified: isonicotinic acid 1 , isonicotinamide 2 and isonicotinaldehyde 3 , the acid being the major product. The oxidation of INH with Mn III -pyrophosphate was carried out in either H 2 16 O, or H 2 18 O or D 2 O and under varied atmosphere composition (argon, air, O 2 or 18 O 2 ). LC–MS analyses of isotope incorporation suggest the simultaneous presence of two competitive pathways leading to the formation of acid 1 , with the isonicotinoyl radical as a common intermediate. One route is oxygen-dependent and the other is water-dependent. Analyses of isotope incorporation in amide 2 and aldehyde 3 also support this mechanism.