ERDC TR-09-3
(Strategic Environmental Research and Development Program)
Sensitivity Analysis of QSAR Models for Assessing Novel Military Compounds
by Jay L. Clausen, Erin Bennett, and Igor Linkov
Abstract:
Reliable estimates of physical and biochemical properties of novel energetic compounds are essential before making the investment to synthesize, scale-up, and manufacture a new material for use in either military or civilian applications. Quantitative Structure-Activity Relationship (QSAR) software tools are available for predicting the physicochemical properties and environmental impacts of these emerging materials. The uncertainty and variability in melting point, solubility, half-lives, and related properties as a means of determining whether QSAR tools could provide meaningful results were evaluated. In particular, the octanol-water partition coefficient (Kow or log P) was estimated for several pro-posed compounds. Log P was selected both because it typically can be measured with a high degree of certainty and because it correlates highly with water solubility and bioaccumulation. This study tested: 1) the variability in QSAR model predictions resulting from potential structural vari-ants in emerging chemicals; and 2) the uncertainty from six different commercial Kow calculators: KOWWIN, MarvinSketch, ACD/Labs, CLogP, SPARC, and ALOGPs. Analyses were performed on three military com-pounds [hexahydro-1,3,5-trinitro-1,3,
5-triazine (RDX), butanetriol trini-trate (BTTN), and 2,4,6-trinitrotoluene (TNT)] and two pesticides [1-chloro-3-ethylamino-5-isopropylamino-2,4,6-triazine (atrazine) and di-chlorodiphenyldichloroethylene (DDE)]. Analyses of these compounds revealed that the uncertainty due to structural variations can be several orders of magnitude. Variability among the five software packages was as high as 10 orders of magnitude for emerging materials although lower for more well-studied chemicals such as DDE and atrazine. The magnitude of the uncertainty suggests use of existing QSAR models for emerging energetic materials is not appropriate.
If you wish to access/download the document (43 pages, 1.3 mb) in pdf format, the address is: http://libweb.wes.army.mil/uhtbin/hyperion/ERDC-TR-09-3.pdf