2- Metabolism of vinyl chloride – a molecular modelling analysis

Fazlul Huq

Discipline of Biomedical Science, School of Medical Sciences, Faculty of Medicine, The University of Sydney, Australia Telephone: +61 2 9351 9522  Fax: +61 2 9351 9520 E-mail : F.Huq@fhs.usyd.edu.au.

Abstract

Vinyl chloride is a highly toxic industrial chemical that is carcinogenic to both humans and experimental animals. Molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations indicate that the long persistence of vinyl chloride in the environment is due to kinetic inertness. Although chloroethylene oxide is kinetically inert, it is thermodynamically unstable and spontaneously rearranges to more reactive metabolite chloroacetaldehyde. The high kinetic lability and the presence of electron-deficient regions would make chloroacetaldehyde a highly toxic metabolite. Relatively small LUMO-HOMO energy differences suggest that, S-formylmethylcysteine, S-acetylglutathione and N-acetyl-S-(2-hydroxyethyl)cysteine would be kinetically labile and could be quite toxic but are more easily eliminated because of greater solubility in water.

Key words: Vinylchloride, chloroethyleneoxide, chloroacetaldehyde, chloroacetic acid, toxicity, molecular modelling

<<<