ERDC TR-09-3, Strategic Environmental Research and Development Program - Sensitivity Analysis of QSAR Models for Assessing Novel Military Compounds

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 octanolwater partition coefficient (Kow or log P) was estimated for several proposed 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 variants 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 compounds [hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), butanetriol trinitrate (BTTN), and 2,4,6-trinitrotoluene (TNT)] and two pesticides [1chloro-3-ethylamino-5-isopropylamino-2,4,6-triazine (atrazine) and dichlorodiphenyldichloroethylene (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. DISCLAIMER: The contents of this report are not to be used for advertising, publication, or promotional purposes. Citation of trade names does not constitute an official endorsement or approval of the use of such commercial products. All product names and trademarks cited are the property of their respective owners. The findings of this report are not to be construed as an official Department of the Army position unless so designated by other authorized documents. DESTROY THIS REPORT WHEN NO LONGER NEEDED. DO NOT RETURN IT TO THE ORIGINATOR.