title: Assessing the structure-activity relationships of fluorotelomer unsaturated acids and aldehydes with glutathione. Reactivity of glutathione with fluorotelomer unsaturated acids and aldehydes.
abstract: Fluorotelomer alcohols (FTOHs) have been shown to degrade via abiotic and biotic mechanisms to perfluorocarboxylates (PFCAs) which are environmentally persistent and bioaccumulate in humans and wildlife depending on their chain length. Fluorotelomer unsaturated aldehydes (FTUALs) and acids (FTUCAs) are intermediate metabolites that form from the degradation of FTOHs. Their potential for toxicity is not yet defined and may be more significant compared to PFCAs. Past studies have shown that these intermediates form adducts with glutathione (GSH). The purpose of this study was to further assess the reactivity of these intermediate compounds. In vitro experiments were carried out in an aqueous buffer system (pH 7.4) where FTUCAs and FTUALs of varying chain lengths were reacted with GSH. To quantify the reactivity of FTUCAs and FTUALs, unreacted free GSH was derivatized with 5,5'-dithiobis(2-nitrobenzoic acid), its absorbance measured at 412 nm, and the percentage of unconjugated free GSH evaluated over time. EC50 values were obtained for the reactions of GSH with acrolein and methyl methacrylate to assess the accuracy of the method, as well as for acrylic acid, FTUCAs, and FTUALs. The results of this study indicated that α,β-unsaturated aldehydes are comparatively the most reactive and reaction with GSH may be influenced by the length of the fluorinated tail. This is the first study to examine the relationship of FTUCAs and FTUALs with biological nucleophiles by quantifying their intrinsic reactivity.
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Rand
authors.forename: Scott A
authors.initials: SA
authors.lastname: Mabury
mesh_terms: D000143:Acids; D000447:Aldehydes; D001711:Biotransformation; D004785:Environmental Pollutants / Q000138:chemical synthesis / Q000737:chemistry*; D005466:Fluorocarbons / Q000138:chemical synthesis / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000143:Acids; D000447:Aldehydes; D004785:Environmental Pollutants; D005466:Fluorocarbons; D005978:Glutathione