Department Environmental Chemistry

Antimicrobial peptides (AMPs) are increasingly important as a last resort against multi-drug resistant bacteria due to resistance formation towards conventional antibiotics. However, many AMPs were introduced to the market before environmental risk assessment was required, e.g., by the European Medicines Agency (EMA) since 1998. While AMPs have been administered as antibiotics and growth promotors in feedstock since the 1960s and were reconsidered for human medicine by the EMA in 2013, details about their mobility and persistence in the environment remain unknown. This study investigated the environmental fate of three commonly used AMPs: bacitracins, daptomycin, and polymyxins B and E (Colistin). We observed moderate sorption affinity of daptomycin to standard European soils (K_d = 20.6–48.6), while polymyxins adsorbed irreversibly. Bacitracin variants sorbed slightly to sandy soil (K_d = 5.8–8) and significantly to clayey soil (K_d = 169–250). We further investigated photochemical and microbial transformation processes relevant in surface waters. We demonstrated that phototransformation of all AMPs was enhanced in the presence of dissolved organic matter and fast bimolecular reaction rate constant with singlet oxygen contributed largely to indirect phototransformation (15–41%). Phototransformation product analysis for daptomycin was consistent with expected modifications of the tryptophan and kynurenine moieties. Moreover, riverine biofilm communities demonstrated biotransformation potential for all AMPs. Our findings of sorption behaviour, photo- and biotransformation suggest that these processes play a critical role in the fate of bacitracins, daptomycin, and polymyxins in environmental systems.

The kinetic solvent isotope effect (KSIE) is typically utilized in environmental photochemistry to elucidate whether a compound is susceptible to photooxidation by singlet oxygen (¹O₂), due to its known difference in lifetime in water (H₂O) versus heavy water (D₂O). Here, the overall indirect photodegradation rates of diarylamines in the presence of dissolved organic matter (DOM) were enhanced in D₂O to a greater extent than expected based on their reactivity with ¹O₂. For each diarylamine, the relative contribution of reaction with ¹O₂ to the observed KSIE was determined from high resolution data of ¹O₂ lifetimes by time-resolved infrared luminescence spectroscopy. The additional enhancement in D₂O beyond reaction with ¹O₂ contributed significantly to the observed KSIE for diarylamines (8–65%) and diclofenac (100%). The enhancement was ascribed to slower reduction of transient radical species of the diarylamines due to H/D exchange at DOM's phenolic antioxidant moieties. A slower second-order reaction rate constant with a model antioxidant was verified for mefenamic acid radicals using transient absorption spectroscopy. Changes in lifetime and reactivity with triplet sensitizers were not responsible for the additional KSIE. Other pollutants with quenchable radical intermediates may also be susceptible to such an additional KSIE, which has to be considered when using the KSIE as a diagnostic tool.

Fenamates are a class of non-steroidal anti-inflammatory drugs (NSAIDs) that are not fully removed during wastewater treatment and can be released to surface waters. Here, near-surface photochemical half-lives were evaluated to range from minutes to hours of four fenamates and the closely related diclofenac. While quantum yields for direct photochemical reactions at the water surface vary widely from 0.071 for diclofenac to <0.001 for mefenamic acid, all fenamates showed significant reactivity towards singlet oxygen and hydroxyl radical with bimolecular reaction rate constants of 1.3-2.8 x 10⁷ M^-1 s^-1 and 1.1-2.7 x 10¹⁰ M^-1 s^-1, respectively. Photodecay rates increased in the presence of dissolved organic matter (DOM) for diclofenac (+19%), tolfenamic acid (+9%), and mefenamic acid (+95%), but decreased for flufenamic acid (-2%) and meclofenamic acid (-14%) after accounting for light screening effects. Fast reaction rate constants of all NSAIDs with model triplet sensitizers were quantified by laser flash photolysis. Here, the direct observation of diphenylamine radical intermediates by transient absorption spectroscopy demonstrates one-electron oxidation of all fenamates. Quenching rate constants of these radical intermediates by ascorbic acid, a model antioxidant, were also quantified. These observations suggest that the balance of oxidation by photoexcited triplet DOM and quenching of the formed radical intermediates by antioxidant moieties determines whether net sensitization or net quenching by DOM occurs in the photochemical degradation of fenamates.