Interactions of Fluoroquinolone Antibacterial Agents with Aqueous Chlorine: Reaction Kinetics, Mechanisms, and Transformation Pathways

Citations Over TimeTop 10% of 2005 papers

Abstract

Kinetics, products, and mechanistic aspects of reactions between free available chlorine (HOCl/OCl-), ciprofloxacin (CF), and enrofloxacin (EF) were extensively investigated to elucidate the behavior of fluoroquinolone antibacterial agents during water chlorination processes. Although the molecular structures of these two substrates differ only with respect to degree of N(4) amine alkylation, CF and EF exhibit markedly different HOCl reaction kinetics and transformation pathways. HOCl reacts very rapidly at CF's secondary N(4) amine, forming a chloramine intermediate that spontaneously decays in aqueous solution by concerted piperazine fragmentation. In contrast, HOCl reacts relatively slowly at EF's tertiary N(4) amine, apparently forming a highly reactive chlorammonium intermediate (R3N(4)Cl+) that can catalytically halogenate EF or other substrates present in solution. Flumequine, a fluoroquinolone that lacks the characteristic piperazine ring, exhibits no apparent reactivity toward HOCl but appears to undergo facile halodecarboxylation in the presence of R3N(4)Cl+ species derived from EF. Measured reaction kinetics were validated in real water matrixes by modeling CF and EF losses in the presence of free chlorine residuals. Combined chlorine (CC) kinetics were determined under selected conditions to evaluate the potential significance of reactions with chloramines. CF's rapid kinetics in direct reactions with HOCl, and relatively high reactivity toward CC, indicate that secondary amine-containing fluoroquinolones should be readily transformed during chlorination of real waters, whether applied chlorine doses are present as free or combined residuals. However, EF's slower HOCl reaction kinetics, recalcitrance toward CC, and participation in the catalytic halogenation cycle described herein suggest that tertiary amine-containing fluoroquinolones will be comparatively stable during most full-scale water chlorination processes.

Related Papers

• → A sensitive and selective assay for chloramine production by myeloperoxidase(2005)171 cited
• → Kinetic Analysis of the Role of Histidine Chloramines in Hypochlorous Acid Mediated Protein Oxidation(2005)100 cited
• → Elevated levels of chloramines and chlorine detected near an indoor sports complex(2022)13 cited
• → Hydrogen peroxide-induced apoptosis of HL-60 human leukemia cells is mediated by the oxidants hypochlorous acid and chloramines(2002)32 cited
• → Relative reactivities of model chloramines and hypochlorous acid with human plasma constituents(1999)