Reactivity and transformation of antibacterial N-oxides in the presence of manganese oxide

Organic N-oxides are an important structural class in many pharmaceutical and industrial chemicals. Little is known about the potential transformation of organic N-oxides at the sediment-water interface. Veterinary antibacterial agents carbadox and olaquindox are examples of commonly used heterocyclic N-oxides. Investigation with various N-oxides including carbadox, olaquindox, quinoline xide, and quindoxin revealed surprisingly high reactivity toward MnO2 for all of the compounds except olaquindox. Desoxycarbadox and quinoxaline two structurally related compounds that lack an N-oxide functional group, showed much lower or no reactivity toward MnO2. Comparisons among the previous compounds indicate that N-oxide moiety is the primary reactive site to MnO2, and substitution at the alpha-C adjacent to the N-oxide group is critical in determining the overall reactivity. Reactions of N-oxides with MnO2 appeared to be oxidation,with generation of Mn2+ parallel to degradation of the parent organics. Product characterization confirmed that quinoline N-oxide and quindoxin transformed into 2-hydroxyquinoline and quinoxaline 2,3-diol, respectively, in reactions with MnO2. The transformation involves separate steps of N-oxide moiety deoxygenation and neighboring alpha-C hydroxylation as elucidated by 180 isotope experiments. All of the experimental results pointed to a mechanism that involves an N-oxide radical intermediate. This is the first study to report such transformation reactivity of organic N-oxides toward manganese oxide, offering a new degradation pathway that could be important for the fate of this group of compounds in the aquatic environment.