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Some reactive properties of chlorooxirane, a likely carcinogenic metabolite of vinyl chloride
Author(s) -
Laurence Patricia 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.560250305
Subject(s) - epoxide , protonation , chemistry , nucleophile , vinyl chloride , photochemistry , chlorine , molecule , computational chemistry , reactivity (psychology) , oxygen , ab initio , chloride , medicinal chemistry , organic chemistry , ion , catalysis , medicine , polymer , alternative medicine , pathology , copolymer
We have carried out a computational study of the reactive properties of chlorooxirane, the metabolically produced epoxide of vinyl chloride that is believed to be a direct‐acting carcinogenic form of this molecule. An ab initio SCF‐MO procedure (GAUSSIAN 70) was used to compute the energy requirements for stretching the CCl and both CO bonds ( S N 1 reactivity) and to determine the course of the epoxide's possible S N 2 reactions with ammonia, taken as a model for nucleophilic sites on DNA. The epoxide was assumed to be protonated; both the oxygen‐ and chloro‐protonated forms were considered. At each step along the various reaction pathways, the structure of the system was reoptimized. For the oxygen‐protonated epoxide, the C 1 O bond has a significantly lower energy barrier to stretching than does the C 2 O. (The carbon bearing the chlorine is designated C 1 .) However, both are very much higher than that of the CCl bond in the chloro‐protonated form, confirming our earlier finding of the relative weakness of this bond. In the S N 2 processes involving ammonia, intermediate complexes are formed with both carbons of the oxygen‐protonated epoxide, the C 2 ‐complex being the more stable. However, the most stable ammonia complex occurs at C 1 of the chloro‐protonated epoxide. Our calculated results, both the energies and also the geometry changes, allow us to propose two possible mechanisms for the formation of the 7‐N‐(2‐oxoethyl) derivative of guanine that has been observed to be the major in vivo DNA alkylation product of vinyl chloride and has been suggested as possibly being responsible for its carcinogenicity. One of these mechanisms is S N 1 and starts with the chloro‐protonated epoxide; the other is S N 2 and involves the oxygen‐protonated form.