title: Formation, stability, and rearrangements of the glutathione conjugates of butadiene monoxide: evidence for the formation of stable sulfurane intermediates.
abstract: Butadiene monoxide, a toxic metabolite of 1,3-butadiene, is a substrate for the human placental glutathione (GSH) S-transferase. The products have been identified as S-(2-hydroxy-3-buten-1-yl)glutathione (I) and S-(1-hydroxy-3-buten-2-yl)glutathione (II). S-(4-hydroxy-2-buten-1-yl)glutathione (III), which was formed chemically, was not detected. 1H NMR analysis of II was consistent with its structure, but spectra of I indicated a 1:1 equilibrium between I and the sulfurane tautomer (IVB) formed by intramolecular displacement of the hydroxyl group by the sulfur atom. The ratio of I to IVB did not change whether the spectrum was obtained at pH 3, 7, or 9 in the presence or absence of LiClO4. Incubations of I at pH 7 or 9 for 5 days at 25 degrees C or for 7 h at 50 degrees C, in the presence or absence of nucleophiles plus LiClO4, did not affect the HPLC profile of I. Storage of I at -20 degrees C for 30 weeks, reflux at pH 7.8 for 5 h in the presence of GSH, or incubations at pH 2 for 5 h at 55 degrees C in the presence of GSH or 2-mercaptoethanol, however, resulted in the conversion of I to III (10-30%). Treatment of I with H2O2 resulted in formation of the corresponding sulfoxide (V) and sulfone (VI), which blocked the formation of III. NMR and chemical reactivity studies of III indicated an initial 1:1 equilibrium between III and the five-membered ring sulfurane (VIIB) formed by intramolecular displacement of the hydroxyl group by the sulfur atom.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, Madison 53706.
authors.forename: J E
authors.initials: JE
authors.lastname: Sharer
authors.forename: R J
authors.initials: RJ
authors.lastname: Duescher
authors.forename: A A
authors.initials: AA
authors.lastname: Elfarra
mesh_terms: D004355:Drug Stability; D004852:Epoxy Compounds / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction
chemical_list: D004852:Epoxy Compounds; C024370:3,4-epoxy-1-butene; D005982:Glutathione Transferase; D005978:Glutathione