Aqueous chlorination of levofloxacin: kinetic and mechanistic study, transformation product identification and toxicity.

The aim of this study was to gain further insight into the fate of levofloxacin during the chlorination process. First, a kinetic study was thus performed at pH 7.2, 20 °C and in the presence of an excess of total chlorine. A slower apparent removal of levofloxacin (k ~ 26 M(-1) s(-1)) was noted when sodium thiosulfate was used to stop the chlorination reaction compared to the degradation observed without using a reducing agent (k ~ 4400 M(-1) s(-1)). The formation of a chlorammonium intermediate which could be converted back into the parent compound through a reaction with thiosulfate was thus expected. This intermediate would result from an initial chlorine attack on the tertiary amine function of levofloxacin. Secondly, four chlorination transformation products were detected by LC/UV/MS analysis. The chemical structures of two of them are proposed. It was suggested that these compounds could come from a secondary reaction of the chlorammonium intermediate on levofloxacin. A reactional pathway is then proposed. Finally, a bioassay using Vibrio fisheri was carried out to study the toxicity pattern during levofloxacin chlorination. An increase in toxicity was observed during chlorination suggesting that the first transformations products formed were more toxic than the parent compound.

Effect of some parameters on the rate of the catalysed decomposition of hydrogen peroxide by iron(III)-nitrilotriacetate in water.

The decomposition rate of H(2)O(2) by iron(III)-nitrilotriacetate complexes (Fe(III)NTA) has been investigated over a large range of experimental conditions: 3 < pH < 11, [Fe(III)](T,0): 0.05-1 mM; [NTA](T,0)/[Fe(III)](T,0) molar ratios : 1-250; [H(2)O(2)](0): 1 mM-4 M) and concentrations of HO· radical scavengers: 0-53 mM. Spectrophotometric analyses revealed that reactions of H(2)O(2) with Fe(III)NTA (1 mM) at neutral pH immediately lead to the formation of intermediates (presumably peroxocomplexes of Fe(III)NTA) which absorb light in the region 350-600 nm where Fe(III)NTA and H(2)O(2) do not absorb. Kinetic experiments showed that the decomposition rates of H(2)O(2) were first-order with respect to H(2)O(2) and that the apparent first-order rate constants were found to be proportional to the total concentration of Fe(III)NTA complexes, were at a maximum at pH 7.95 ± 0.10 and depend on the [NTA](T,0)/[Fe(III)](T,0) and [H(2)O(2)](0)/[Fe(III)](T,0) molar ratios. The addition of increasing concentrations of tert-butanol or sodium bicarbonate significantly decreased the decomposition rate of H(2)O(2), suggesting the involvement of HO· radicals in the decomposition of H(2)O(2). The decomposition of H(2)O(2) by Fe(III)NTA at neutral pH was accompanied by a production of dioxygen and by the oxidation of NTA. The degradation of the organic ligand during the course of the reaction led to a progressive decomplexation of Fe(III)NTA followed by a subsequent precipitation of iron(III) oxyhydroxides and by a significant decrease in the catalytic activity of Fe(III) species for the decomposition of H(2)O(2).