Formation of bioactive transformation products during glucocorticoid chlorination

摘要: Glucocorticoid (GC) release into the environment has led to widespread detection of glucocorticoid receptor (GR) activity in water resources that been shown persist throughout conventional and some advanced wastewater treatment processes. Here, we used high performance liquid chromatography, resolution mass spectrometry nuclear magnetic resonance spectroscopy explore reaction natural (cortisone, cortisol) synthetic (prednisone, prednisolone, dexamethasone) GCs with free chlorine (HOCl) simulate their fate during chemical disinfection wastewater. Generally, react slowly (t1/2 ∼ 7–200 h) HOCl when compared other steroid classes, but they yield complex mixtures transformation products, at times majority product comprising structurally identifiable likely bioactive steroids. For example, frequently observed chlorination C-9 position (e.g., 9-chloro-prednisone), a known increase GC 4-fold. We also identified products adrenosterone family androgens produced via cleavage C-17 side-chain on many GCs. Another common pathway was conversion endogenous more potent analogs oxidation C-1/C-2 positions, unsaturation reported GR 4-fold cortisol prednisolone). Despite identification such vitro assays generally suggest decreases extent parent decay chlorination. Cortisol exception, only decreasing 2-fold (based measured EC50 values) despite 95% reduction concentration, result attributable formation prednisolone Furthermore, our assay underestimates bioactivity as it did not account for several byproducts first require vivo activation C-11 reduction, nor consider androgen (AR) associated from family. To avoid conserved bioactivity, processes may represent promising approach; show much rapidly ozone 0.4–1.3 min) produce no observable UV-active products. This suggests disruption conjugated π-electron ring systems, thereby mitigating biological activity.