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Reactive properties of trans ‐dichlorooxirane in relation to the contrasting carcinogenicities of vinyl chloride and trans ‐dichloroethylen
Author(s) -
Laurence Patricia R.,
Proctor Timothy R.,
Politzer Peter
Publication year - 1984
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560260310
Subject(s) - epoxide , chemistry , protonation , adduct , vinyl chloride , nucleophile , chlorine , reactivity (psychology) , molecule , ab initio , chloride , oxygen , double bond , ammonia , computational chemistry , photochemistry , medicinal chemistry , polymer chemistry , organic chemistry , catalysis , ion , medicine , polymer , alternative medicine , pathology , copolymer
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 CO and CCl bonds ( S N 1 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 CCl bonds are found to have much lower energy barriers to stretching than do the oxygen‐protonated CO 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 S N 1 and the other S N 2) whereby trans ‐dichlorooxirane can interact with N 7 of guanine to produce an adduct analogous to one formed by chlorooxirane, which has been found to be the primary in vivo DNA alkylation product of vinyl chloride and to which has been attributed the carcinogenicity of the latter. Overall, trans ‐dichlorooxirane is found to be chemically more reactive than chlorooxirane; 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.