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01- Semi-empirical and DFT analyses of the metabolism
of hydrazine
Fazlul Huq
School
of Biomedical Sciences, Faculty of Health Sciences, The University of
Sydney
Correspondences author: Dr. Fazlul Huq,
School
of Biomedical Sciences, Faculty of Health Sciences, C42, The
University of Sydney,
PO
Box 170, Lidcombe, NSW 1825, Australia.
Telephone: +61 2 9351 9522 F Fax: +61 2 9351 9520
E-mail :
f.huq@fhs.usyd.edu.au
Abstract:
Hydrazine is a highly used but toxic industrial chemical that causes
fatty liver and in some cases liver necrosis, CNS disturbances and
tumours in various organs. It is remarkably stable even though it has
high (positive) heat of formation. Molecular modelling analyses based
on semi-empirical and DFT calculations show that although the reaction
in which hydrazine decomposes to nitrogen and hydrogen is spontaneous,
the relatively large kinetic barrier imparts stability to hydrazine
molecule. However, since the reaction is highly exothermic, once it
starts, it would speed up quickly. The metabolites THOPC and pyruvate
hydrazone have relatively small LUMO-HOMO differences indicating that
the two compounds would be the most reactive metabolites of hydrazine.
The presence of some electron-deficient regions on the molecular
surfaces of hydrazine and its metabolites indicate that they may react
with cellular glutathione and can cause oxidation of nucleobases in
DNA. However, the kinetic inertness of the molecules suggests that the
effects of such adverse reactions would be low unless the reactions
are speeded up enzymatically.
Key words:
Hydrazine, pyruvate hydrazone, urea, toxicity, molecular modelling
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