Interactions between sulfonamide antibiotics and metal ions: does toxicity increase or decrease?

With the increasing occurrence of multiple pollutants in aquatic environments, interactions among coexisting contaminants and their combined environmental effects have attracted considerable attention. Among these interactions, the coexistence of antibiotics and metal ions is widespread; however, the effects of antibiotic-metal interactions on photochemical behavior and biological toxicity remain insufficiently understood. In this study, two representative sulfonamide antibiotics, sulfadiazine (SDZ) and sulfamethoxazole (SMX), together with three environmentally relevant metal ions (Fe(iii), Al(iii), and Cu(ii)), were selected to investigate changes in spectroscopic characteristics, physicochemical properties, and toxicity following metal binding. Toxicity was evaluated using the Vibrio fischeri bioluminescence inhibition assay. FTIR analysis suggested that the pyrimidine nitrogen atom of SDZ and the sulfonamide nitrogen and sulfonyl oxygen atoms of SMX may participate in metal binding. UV-vis spectra showed pH-dependent red or blue shifts and changes in absorption intensity, indicating that metal interaction altered the electronic environment of sulfonamides. SDZ showed a greater tendency to interact with metal ions under acidic conditions, whereas SMX favored interaction under neutral conditions. Among the investigated metal ions, the apparent interaction strength with sulfonamides followed the order Fe(iii) > Cu(ii) > Al(iii). Metal binding was associated with enhanced fluorescence intensity, which may be attributed to increased molecular rigidity and reduced non-radiative energy dissipation. Toxicity assays revealed that the toxicity of sulfonamides generally decreased after interaction with metal ions. Especially, when the intrinsic toxicity of a metal ion exceeded that of the corresponding antibiotic, the observed toxicity of the equilibrated metal-antibiotic system was lower than the sum of the individual toxicities. Overall, interactions between sulfonamide antibiotics and metal ions significantly influence their spectroscopic behavior and toxicity, with important implications for contaminant fate, bioavailability, environmental risk assessment, and remediation strategies in aquatic environments.