Sequential exposure to anoxic/oxic conditions leads to biotransformation and detoxification of sitagliptin in urban hyporheic zones

Pharmaceuticals are increasingly recognized as contaminants of concern in aquatic environments. Sitagliptin, an antidiabetic drug that carries a trifluoromethyl group, which is a precursor of the persistent trifluoroacetic acid, is excreted largely unmetabolized and inefficiently removed in wastewater treatment plants, leading to its widespread detection in surface waters. The hyporheic zone -- a region between surface water and groundwater -- serves as a natural bioreactor with high microbial activity and diverse redox conditions, offering the potential for sitagliptin attenuation. This study explored the biotransformation of sitagliptin in hyporheic sediments under varying redox conditions through batch experiments and field observations. Furthermore, we showed that batch experiments can complement field observations to capture both mechanistic insights and their environmental relevance. Batch experiments revealed amide hydrolysis and N-acetylation of sitagliptin under anoxic conditions, with subsequent deamination and oxidation of transformation products under oxic conditions. Metagenome-resolved metaproteomics suggested Pseudomonas asiatica as a key player in the oxic transformation. Field analysis of pore water samples identified up to 6.47 {micro}g L-{superscript 1} sitagliptin and ten transformation products with concentrations of up to 4.82 {micro}g L-{superscript 1}. Amide hydrolysis products were the most abundant transformation products and preferentially formed under anoxic conditions. All investigated transformation products exhibited lower cytotoxicity and oxidative stress response than sitagliptin in in vitro bioassays, highlighting the detoxification potential of the hyporheic zone. By identifying conditions that promote sitagliptin transformation and characterizing its transformation products toxicologically, our work provides parameters for enhanced sitagliptin removal in aquatic environments and improved risk assessment of fluorinated trace organic contaminants. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/657625v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@b43cf4org.highwire.dtl.DTLVardef@10dd64eorg.highwire.dtl.DTLVardef@170ca9corg.highwire.dtl.DTLVardef@5e433_HPS_FORMAT_FIGEXP M_FIG C_FIG