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11- Molecular modelling analysis of the metabolism of
carbon tetrachloride
Fazlul Huq
School of
Biomedical Sciences, Faculty of Health Sciences, The University of
Sydney,
Australia.
Telephone: +61 2 9351 9522 Fax: +61 2 9351 9520
E-mail :
f.huq@fhs.usyd.edu.au.
Abstract
Carbon tetrachloride is a potent hepatotoxin, causing increased liver
weight, lipid peroxidation, fatty infiltration and liver necrosis. It
is carcinogenic to animals and classified as a probable human
carcinogen. Molecular modelling analyses based on molecular mechanics,
semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations show
that carbon tetrachloride and all its metabolites have moderately
large to large LUMO-HOMO energy differences so that they would be
kinetically inert except :CCl2 and carbon monoxide which
have much smaller values. Thus the persistence of CCl4 and
its metabolites in the environment is due to their kinetic inertness.
The molecular surface of CCl2 has significant amount of
electron-deficient blue regions so that it can react readily with
glutathione and nucleobases in DNA, thus causing inducing cellular
toxicity due to glutathione depletion and DNA damage due to oxidation
of nucleobases in DNA.
Key words:
Carbon tetrachloride, trichloromethyl free radical, hexachloroethane,
toxicity, molecular modelling
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