Oxidative Transformation of Fluoroquinolone Antibacterial Agents and Structurally Related Amines by Manganese Oxide

Abstract

Various members of the popular fluoroquinolone antibacterial agents (FQs) have been frequently detected in municipal wastewater and surface water bodies in recent years. This study was conducted to gain a better understanding of the fate of FQs in the sediment−water environment. Seven FQs were examined for adsorptive and oxidative interactions with δ-MnO₂ under environmental conditions and exhibited reactivity in the order of ciprofloxacin ∼ enrofloxacin ∼ norfloxacin ∼ ofloxacin > lomefloxacin > pipemidic acid ≫ flumequine. Four amines that are structurally related to the aniline and piperazine functional groups of FQs showed reactivity to oxidation by δ-MnO₂ in the order of 1-phenylpiperazine > aniline > N-phenylmorpholine > 4-phenylpiperidine. Comparison among the above compounds clearly indicates that the piperazine moiety of FQs is the predominant adsorptive and oxidative site to MnO₂. Product analyses showed that oxidation by MnO₂ results in dealkylation and hydroxylation at the piperazine moiety of FQs, with the quinolone ring essentially intact. The reaction kinetics, reactivity comparison, and product characterization point to a surface reaction mechanism that likely begins with formation of a surface complex between FQ and the surface-bound Mn^IV, followed by oxidation at the aromatic N₁ atom of FQ's piperazine moiety to generate an anilinyl radical intermediate. The radical intermediates subsequently undergo N-dealkylation, C-hydroxylation, and possibly coupling to yield a range of products. Even though the quinolone ring appears to be stable with respect to MnO₂, it affects the overall reactivity and potentially product distribution of FQs via substituent effects. Results of this study strongly suggest that manganese oxides commonly present in soils will likely play an important role in the abiotic degradation of fluoroquinolone antibacterial agents in the environment.