Transformation of ß-lactam antibiotics during water chlorination: reaction kinetics and product identification

Abstract

Beta-lactam antibiotics are among the most widely used antibacterial agents globally. They have been found to persist in the environment, and their complete elimination is challenging during water and wastewater treatment processes. Chlorine is widely applied as a water disinfectant, and can degrade beta-lactam antibiotics, however, the related reaction chemistry and change of antibacterial activity have not been well understood. This study investigated the reaction of two beta-lactam antibiotics, i.e. penicillin G (PG) and cephalexin (CP), with chlorine. Using direct and competition kinetics methods, the apparent second-order rate constants (kapp) were determined for the reaction of free available chlorine species with PG and CP. Both PG and CP exhibited high reactivity towards aqueous chlorine (kapp = 1.6 × 104 M-1 s-1 and 6.1 × 105 M-1 s-1 at pH 7, respectively). The thioether moiety was the major reactive site for PG, while the thioether and amine moieties were the reactive sites for CP. The thioether moiety was transformed to stereoisomeric sulfoxide group (~15% yield for PG-R-sulfoxide, ~36% yield for CP-R-sulfoxide, and ~9% yield for CP-S-sulfoxide). A newly detected compound resulting from the beta-lactam ring opening and carbon-sulfur bond cleavage was detected for PG. The major reaction pathways during CP chlorination are S- and N-chlorination, elimination, hydrolysis, and chlorine substitution. Overall, chlorination was found to be efficient to degrade beta-lactam antibiotics, which warrants further investigation in real water matrices.