A mechanistic investigation of the environmental chemodynamics of fluoroquinolone antibiotics

Fluoroquinolones (FQs), commonly used in human and veterinary medicine due to their broad spectrum of antibacterial activity, can affect biogeochemical processes mediated by soil bacteria and both the growth and morphology of aquatic photosynthetic organisms. These antibiotics bind strongly to mineral and organic constituents of soils, which influence their environmental degradation and bioavailability. Focusing on the common FQ ciprofloxacin (Cipro), both modeling and experimental techniques were employed to explore its mechanisms of interactions with metal cations and natural organic matter (NOM) and to determine its potential toxicological targets in photosynthetic organisms. Molecular modeling of Cipro complexation with Ca2+, Mg 2+, and Fe2+ resulted in bidendate chelates whereby the Fe-Cipro and Mg-Cipro complexes would be the most stable within clay minerals and NOM. Simulations of Cipro within humic substance (HS) sorbents showed that H-bonding interactions with HS moieties and outer-sphere complexes with an HS-bound metal cation were important in forming the most thermodynamically-favorable complexes with HS-Mg and HS-Fe(II). Sorption experiments of Cipro with HS from terrestrial and aquatic sources, which were conducted to monitor the predicted theoretical interactions under acidic and alkaline pH conditions, confirmed electrostatic interactions between cationic Cipro species and HS ligands whereby Cipro sorption was impeded in the presence of divalent cations. The terrestrial HS exhibited up to three times higher sorption capacity than the aquatic HS, which led to the hypothesis that electrostatic and H-bonding interactions are prevalent with the aquatic HS whereas the high aromaticity of terrestrial HS facilitates, in addition, favorable pi-pi interactions. To determine toxicological targets, structure-activity relationship analyses with well-known photosynthetic substrates indicate that FQs possess structural features found in compounds that target photosystem II (PSII). Experimental assays with spinach plants exposed to Cipro resulted in stunted plant growth and inhibition of the PSII photochemical process implying that FQs may inhibit chloroplast replication via a mechanism similar to its antibacterial action and, additionally, interfere with the photosynthetic electron transport. This research presents the mechanisms by which FQs can be sequestered and protected from degradation within soils whereas they can be bioavailable in aquatic systems and interfere with the health of aquatic photosynthetic habitats.