There is considerable evidence indicating that the carcinogenic action of vinyl chloride involves metabolic conversion to the epoxide (chlorooxirane) as the initial step. In order to learn more about its subsequent behavior, we have computed structures, energies and other properties for two different protonated forms of the epoxide, and also for two possible rearrangement products, chloroacetaldehyde and acetyl chloride. An ab initio SCF-MO procedure (GAUSSIAN 70) was used. Oxygen protonation is found to weaken both C -0 bonds, the effect being greater for the bond involving the carbon bearing the chlorine. Chlorine protonation leads to a marked weakening of the C-CI bond; this suggests a possible loss of HCI, leaving behind a carbonium ion (and possible alkylating agent or rearrangement precursor). Thus, while C-0 bond breaking is doubtless an important reaction pathway for chlorooxirane, our results indicate that attention should also be focused upon the C-CI bond; its rupture may conceivably be a key step in the biological action of vinyl chloride.

Our objective in this work is to gain insight into the contrasting carcinogenic activities of vinyl chloride (definitely carcinogenic) and trans-dichloroethylene (apparently inactive). The initial metabolic step for each molecule is believed to be epoxidation of the double bond, and there is evidence indicating that for vinyl chloride, this epoxide (chlorooxirane) is its ultimate (direct-acting) carcinogenic form. This article presents the findings of a computational study of the reactive properties of trans-dichlorooxirane (the epoxide of trans-dichloroethylene). An ab initio SCF-MO procedure was used to determine the energy requirements for stretching the C-0 and C-CI bonds (SN1 reactivity) and to study the epoxide's S N 2 interactions with ammonia, taken as a model nucleophile. The starting points were the oxygen-and chlorine-protonated forms of the epoxide. The structure of the system was reoptimized at each step along the various reaction pathways. The results of this work are compared to an analogous earlier study of the reactive properties of chlorooxirane. The chlorineprotonated C-CI bonds are found to have much lower energy barriers to stretching than do the oxygen-protonated C-0 bonds. In the S N 2 processes, intermediate complexes are formed with ammonia by both the oxygen-and the chlorine-protonated epoxides; the latter complexes are the more stable. Based on our results, we propose two mechanisms (one SN 1 and the other SN2) whereby trans-dichlorooxirane can interact with N7 of guanine to produce an adduct analogous to one formed by chlorooxirane, which has been found to be the primary in uivo DNA alkylation product of vinyl chloride and to which has been attributed the carcinogenicity of the latter. Overall, transdichlorooxirane is found to be chemically more reactive than chiorooxirane; this may help to account for the much lesser carcinogenic and mutagenic activities of trans-dichloroethylene, since the epoxide may be reacting with other cellular nucleophiles before it reaches the key site(s) at which the carcinogenic or mutagenic interaction would occur. We also offer some speculations concerning other possible factors related to the differing carcinogenicities of vinyl chloride and trans-dichloroethylene, such as ease of epoxide formation and the likelihood of oxygen protonation.