2.
Molecular modelling insight into toxicity of ethylene oxide
Fazlul Huq
Discipline of Biomedical Science, School of
Medical Sciences, Faculty of Medicine, Cumberland Campus, C42, The
University of Sydney, Lidcombe, NSW, Australia.
Phone: +61 2 9351 9522; Fax: +61 2 9351 9520 Email:
F.Huq@usyd.edu.au
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.
Key words: Ethylene oxide, genotoxic, carcinogenic,
molecular modelling
<<< |