title: Microsomal oxidation of tribromoethylene and reactions of tribromoethylene oxide.
abstract: Halogenated olefins are of interest because of their widespread use in industry and their potential toxicity to humans. Epoxides are among the enzymatic oxidation products and have been studied in regard to their toxicity. Most of the attention has been given to chlorinated epoxides, and we have previously studied the reactions of the mono-, di-, tri-, and tetrachloroethylene oxides. To further test some hypotheses concerning the reactivity of these compounds, we prepared tribromoethylene (TBE) oxide and compared it to trichloroethylene (TCE) oxide and other chlorinated epoxides. TBE oxide reacted with H(2)O about 3 times faster than did TCE oxide. Several hydrolysis products of TBE oxide were the same as formed from TCE oxide, i.e., glyoxylic acid, CO, and HCO(2)H. Br(2)CHCO(2)H was formed from TBE oxide; the yield was higher than for Cl(2)CHCO(2)H formed in the hydrolysis of TCE oxide. The yield of tribromoacetaldehyde was < 0.4% in aqueous buffer (pH 7.4). In rat liver microsomal incubations containing TBE and NADPH, Br(2)CHCO(2)H was a major product, and tribromoacetaldehyde was a minor product. These results are consistent with schemes previously developed for halogenated epoxides, with migration of bromine being more favorable than for chlorine. Reaction of TBE oxide with lysine yielded relatively more N-dihaloacetyllysine and less N-formyllysine than in the case of TCE oxide. This same pattern was observed in the products of the reaction of TBE oxide with the lysine residues in bovine serum albumin. We conclude that the proposed scheme of hydrolysis of halogenated epoxides follows the expected halide order and that this can be used to rationalize patterns of hydrolysis and reactivity of other halogenated epoxides.
authors.affiliation: Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
authors.forename: Tadao
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Joel A
authors.initials: JA
authors.lastname: Krauser
authors.forename: F Peter
authors.initials: FP
authors.lastname: Guengerich
mesh_terms: D000818:Animals; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015946:Ethylene Dibromide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D005030:Ethylenes / Q000138:chemical synthesis / Q000493:pharmacokinetics; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis / Q000378:metabolism*; D006868:Hydrolysis; D008658:Inactivation, Metabolic / Q000502:physiology*; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats
chemical_list: D004852:Epoxy Compounds; D005030:Ethylenes; D006842:Hydrocarbons, Brominated; C036489:trichloroepoxyethane; D015946:Ethylene Dibromide; C474462:ethylene tribromide