A QSAR Approach to Physico-Chemical Data for Organophosphates with Special Focus on Known and Potential Nerve Agents

Internet Electronic Journal of Molecular Design 2004, xxxx 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 modelling 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 for physico-chemical properties of nerve agents are based on the use of the EPI Suite. Partial order ranking is an important tool to establish an identity for nerve agents relative to well-know OP insecticides. The development of a simple QSAR model for toxicological properties was unsuccessful. Method. 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. Results. “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 Conclusions. The paper suggests that experimentally well-characterized compounds may be selected as substitutes for highly toxic compounds for preliminary experimental studies. Availability. The reference manual for the EPI Suite: P2 Manual 6-00.pdf' found at http://www.epa.gov/pbt/framwork.htm, The EPI Suite is available at http://www.epa.gov/oppt/exposure/docs/episuitedl.htm