Tetrachloroethylene oxide: hydrolytic products and reactions with phosphate and lysine.
Tetrachloroethylene, or perchloroethylene (PCE), has considerable industrial use and is of toxicological interest because of a variety of effects. Most of the existing literature presents PCE oxide as a critical intermediate in the oxidative metabolism of PCE to Cl(3)CCO(2)H, oxalic acid, and products covalently bound to proteins, including trichloroacetyl derivatives of lysine. PCE oxide was synthesized by photochemical oxidation of PCE and characterized. Decomposition at neutral pH (t(1/2) = 7.9 min at 0 degrees C, 5.8 min at 23 degrees C, 2.6 min at 37 degrees C) yielded only trace ( approximately 1%) Cl(3)CCO(2)H; the major products identified were CO (73% yield) and CO(2) (63% yield). In phosphate buffer (0.10 M) a major product was identified as oxalyl phosphate. Oxalyl chloride also reacted to form CO and CO(2) in aqueous solution and to form oxalyl phosphate in neutral phosphate buffer. Oxalyl phosphate decomposed to oxalic acid (t(1/2) = 53 min at 37 degrees C) but did not react with lysine. Reaction of PCE oxide with free lysine yielded the oxalic acid amide derivatives of lysine plus lysine dimers in which cross-linking of the amino groups involved oxalo linkage. The reaction of PCE oxide with albumin yielded mainly N(6)-oxalolysine and some (<5%) N(6)-trichloroacetyllysine. We propose a reaction pathway for PCE oxide based on our previous studies with trichloroethylene oxide, in which C-C bond scission is a major product of reaction in aqueous buffer and yields CO and CO(2). Oxalyl species are proposed as intermediates and prominent acylating species formed in the reactions of the epoxide. The formation of Cl(3)CCO(2)H in cytochrome P450 reactions is postulated to result from intramolecular migration within an enzyme intermediate.
Yoshioka
Tadao
T
Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Krauser
Joel A
JA
Guengerich
F Peter
FP
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004852:Epoxy Compounds / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008239:Lysine / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
D004852:Epoxy Compounds; D010710:Phosphates; D012710:Serum Albumin, Bovine; C036488:tetrachloroepoxyethane; D008239:Lysine