Transformation of the antibacterial agent sulfamethoxazole in reactions with chlorine: kinetics, mechanisms, and pathways.

Sulfamethoxazole (SMX)--a member of the sulfonamide antibacterial class--has been frequently detected in municipal wastewater and surface water bodies in recent years. Kinetics, mechanisms, and products of SMX in reactions with free chlorine (HOCl/OCl-) were studied in detail to evaluate the effect of chlorination processes on the fate of sulfonamides in municipal wastewaters and affected drinking waters. Direct reactions of free available chlorine (FAC) with SMX were quite rapid. A half-life of 23 s was measured under pseudo-first-order conditions ([FAC]0 = 20 microM (1.4 mg/L) and [SMX]0 = 2 microM) at pH 7 and 25 degrees C in buffered reagent water. In contrast, a half-life of 38 h was determined for reactions with combined chlorine (NH2Cl, NHCl2) under similar conditions. Free chlorine reaction rates were first-order in both substrate and oxidant, with specific second-order rate constants of 1.1 x 10(3) and 2.4 x 10(3) M(-1) s(-1) for SMX neutral and anionic species, respectively. Investigations with substructure model compounds and identification of reaction products verified that chlorine directly attacks the SMX aniline-nitrogen, resulting in (i) halogenation of the SMX aniline moiety to yield a ring-chlorinated product at sub-stoichiometric FAC concentrations (i.e., [FAC]0:[SMX]0 < or = 1) or (ii) rupture of the SMX sulfonamide moiety in the presence of stoichiometric excess of FAC to yield 3-amino-5-methylisoxazole, SO4(2-) (via SO2), and N-chloro-p-benzoquinoneimine. Reaction ii represents an unexpected aromatic amine chlorination mechanism that has not previously been evaluated in great detail. Experiments conducted in wastewater and drinking water matrixes appeared to validate measured reaction kinetics for SMX, indicating that SMX and likely other sulfonamide antibacterials should generally undergo substantial transformation during disinfection of such waters with free chlorine residuals.