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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. May 2005, Volume 4, Number 5, 355-366 |
A QSAR Approach to Physico-Chemical Data for Organophosphates with Special
Focus on Known and Potential Nerve Agents
Lars Carlsen
Internet Electron. J. Mol. Des. 2005, 4, 355-366
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Abstract:
Nerve agents like Sarin, Tabun, Soman, VX, Amiton etc. are highly
toxic organophosphates (OPs) that exert their toxic effect by
inhibition of acetylcholine esterase. These compounds have received
considerable interest due their inherent nature as weapons of mass
destruction. Since these compounds have been developed for
military purposes, data is typically classified material and thus only
scarcely available. QSAR modeling is an obvious possibility in order
to remedy the lack of data availability. However, a wide variety of
structurally related OP insecticides are well known and well
characterized. "Noise-deficient" QSARs, i.e., a QSAR model where
the natural variation in both the experimental data and the primary
models data has been suppressed in a subsequent modeling step, for
physico-chemical properties of nerve agents are based on the use of
the EPI Suite, a general QSAR model from the US EPA. Partial
order ranking is an important tool to establish an identity for nerve
agents relative to well-known OP insecticides. The development of a
simple QSAR model for toxicological properties was unsuccessful.
The results described in the paper are obtained using QSAR
modeling based on the EPI Suite in comparison with partial order
ranking. The concept of "noise deficient" QSARs is introduced.
"Noise deficient" QSARs can be obtained using EPI Suite generated
data in combination with experimental data for the test set, the data
subsequently being applied in the ranking exercise. In the present
study it is shown that to a certain extent selected insecticides may act
as substitutes for nerve agents in preliminary experimental studies.
The paper suggests that experimentally well-characterized
compounds may be selected as substitutes for highly toxic
compounds for preliminary experimental studies of the
environmental behavior of the latter.
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