Mechanism of Aqueous Decomposition of Trichloroethylene Oxide

Abstract

The aqueous decomposition of trichloroethylene (TCE) oxide is shown to involve both pH-independent and hydronium ion-dependent regions. C−C bond scission is a major reaction at all pH values. Disappearance of TCE oxide is the rate-determining step for the formation of CO under the conditions studied. The product distribution of CO and three carboxylic acids (HCO2H, Cl2CHCO2H, and glyoxylic acid) did not change considerably over the pH range of −1.5−14, in general, even though the hydrolysis mechanism changes from hydronium ion-dependent to pH-independent. Mechanisms for the hydronium ion-dependent and pH-independent hydrolysis of TCE oxide were elucidated on the basis of the results of H2 18O and H incorporation and identification of products of the reaction of TCE oxide with lysine in both H2 16O and H2 18O. In the pH-independent hydrolysis, a zwitterionic intermediate could be formed and undergo an intramolecular rearrangement (Cl- shift) to generate dichloroacetyl chloride, which would subsequently decompose to Cl2CHCO2H. The zwitterionic intermediate could also hydrolyze at the less sterically hindered methylene to give a glycol anion, which would dehydrohalogenate to form an oxoacetyl chloride intermediate. The oxoacetyl chloride could hydrolyze to generate either glyoxylic acid, as a final product, or an anionic intermediate, which could go through a concerted mechanism to generate CO, HCO2H, and chloride. A mechanism proposed for the hydronium ion-dependent hydrolysis is very similar to that for the pH-independent hydrolysis except for the first step, which involves hydronium ion attack on TCE oxide to form a TCE-oxide cation intermediate. The lysine amide adducts were characterized by HPLC and mass spectrometry as those resulting from reaction with the postulated acyl chlorides.

Unusual Cytochrome P450 Enzymes and Reactions

“…In addition, vinyl compounds with good leaving groups can form epoxides that rearrange, e.g. to ␣-halocarbonyls (18,19).…”

Cytochrome P450 enzymes in drug metabolism and chemical toxicology: An introduction

“…The oxidation product of pyridine is inactive, but the final product of hexane oxidation, 2,5-hexanedione, can cross-link proteins. To complicate matters, it is also not unusual for multiple products with varying metabolic activity to be formed from P450 reactions on a single substrate as with trichloroethylene [36,37] (Fig. 5C).…”

“…B, during metabolism of other chemicals, P450s may inactivate a toxicant, such as observed with pyridine (solvent) (heteroatom oxygenation), or activate a chemical to a toxic metabolite, as observed with hexane (solvent) (hydroxylation and further oxidation of the alcohols to ketones). C, in some cases, P450s may produce a mixture of deactivated and toxic products, as is the case with trichloroethylene (solvent, common contaminant in waste dumpsites) (epoxidation followed by rearrangement to a more reactive product [36], and olefin oxidation accompanied by a 1,2 migration of chloride ion to the deactivated product chloral, which is actually a sedative [37]). Despite the differences in reaction types, all reaction mechanisms proceed via the generalized P450 catalytic cycle shown in Fig.…”

Identification of Trichloroethylene and Its Metabolites in Human Seminal Fluid of Workers Exposed to Trichloroethylene

“…Humans are efficient at glucuronidating TCOH relative to rodents, although impaired ability for glucuronidation reactions is relatively frequent in the human population (Templin et al, 1993;Green et al, 1997). Recent studies indicated that dichloroacetyl chloride is generated from TCE oxide and can be trapped with lysine to form N ⑀ -dichloroacetyllysine (Cai and Guengerich, 1999). The acyl chloride subsequently decomposes to form dichloroacetic acid (DCA).…”