Complexation facilitated reduction of aromatic N -oxides by aqueous Fe ^II-tiron complex: Reaction kinetics and mechanisms

Rapid reduction of carbadox (CDX), olaquindox and several other aromatic N-oxides were investigated in aqueous solution containing Fe^II and tiron. Consistent with previous work, the 1:2 Fe^II-tiron complex, FeL₂^6-, is the dominant reactive species as its concentration linearly correlates with the observed rate constant k _obs under various conditions. The N-oxides without any side chains were much less reactive, suggesting direct reduction of the N-oxides is slow. UV-vis spectra suggest FeL₂^6- likely forms 5-or 7-membered rings with CDX and olaquindox through the N and O atoms on the side chain. The formed inner-sphere complexes significantly facilitated electron transfer from FeL₂^6- to the N-oxides. Reduction products of the N-oxides were identified by HPLC/QToF-MS to be the deoxygenated analogs. QSAR analysis indicated neither the first electron transfer nor N-O bond cleavage is the rate-limiting step. Calculations of the atomic spin densities of the anionic N-oxides confirmed the extensive delocalization between the aromatic ring and the side chain, suggesting complex formation can significantly affect the reduction kinetics. Our results suggest the complexation facilitated N-oxide reduction by Fe^II-tiron involves a free radical mechanism, and the subsequent deoxygenation might also benefit from the weak complexation of Fe^II with the N-oxide O atom.