Computational Chemistry and Molecular Modeling
Atomic, Molecular and Optical Physics
Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
This article summarizes and extends our computational studies (ab initio, SCF-MO) of the reactive properties of halogenated hydrocarbon epoxides. For five such epoxides (ethylene oxide, propylene oxide, chlorooxirane, trans-dichlorooxirane, and epichlorohydrin), we analyze and compare first the energy requirements for stretching the C—O and C—Cl bonds, and second, the reactivities of the epoxide ring carbons toward a model nucleophile, ammonia. At each step along the various reaction pathways, the structure of the system was reoptimized. The epoxides were taken to be protonated, either on the oxygen or on the chlorine. Ring opening via monomolecular rupture of a C—O bond was found to occur significantly more readily when there is a —CH3 or —Cl substituent on the carbon. Epichlorohydrin is exceptional, in that stretching a C—O bond leads to a movement of the chlorine toward the carbon in question, forming a three- or four-membered ring. The stretching of protonated C—Cl bonds has remarkably low energy requirements, even when the carbon is not part of the epoxide ring. The interactions with ammonia produced intermediate complexes, which are particularly stable when there is a chlorine on the other ring carbon. The formation of the primary in vivo DNA alkylation product of vinyl chloride, suggested as being responsible for the carcinogenicity of the latter, is discussed. The most negative values of the electrostatic potentials near the oxygens of 21 different epoxides are listed and analyzed in terms of their relationship to the nature of the substituent on the epoxide ring. Also discussed are our earlier findings that epoxide carcinogenicity appears to be associated with a relatively strong negative potential near the oxygen, and that the abilities of epoxides to inhibit epoxide hydrase correlate well with this oxygen potential (modified by a parameter to take account of steric effects).
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