Abstract

Although ethylene oxide (EO) is a widely used industrial chemical, being an alkylating agent it is genotoxic and carcinogenic Molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations show that EO and its metabolites have large LUMO-HOMO energy differences ranging from 5.1 to 10.1 eV. The values suggest EO and its metabolites would be inert kinetically. In actual fact, EO is highly reactive in biological systems, suggesting that the reactions of EO with biomolecules such as glutathione, proteins and DNA may be following enzyme-catalysed pathways. That EO is also highly reactive in the environment, points to the limitations of the molecular modelling calculations for an isolated molecule in a vacuum.  

The molecular surface of EO is found to abound in electron-deficient blue regions so that the compound can be subject to nucleophilic attacks. Nucleophilic attacks can be due to glutathione and nucleobases in DNA so that the two compounds may induce cellular toxicity due to glutathione depletion and DNA damage due to oxidation of nucleobases in DNA.