Fully In Silico Calibration Of Empirical Predictive Models For Environmental Fate Properties Of Novel Munitions Compounds
EMSL Project ID
40016
Abstract
Predicting chemical properties is a long-standing challenge that has received extensive study for many applications (chemical engineering, green chemistry, environmental chemistry, toxicology, pharmacology, etc.). For chemical properties that determine the fate and effects of environmental contaminants, the field is mature enough to have already engendered several generations of compilations of predictive models. However, a realistic assessment of the state-of-the-art in this field reveals some pervasive limitations. In particular, most existing property prediction models are based on empirical correlations between the target property and descriptor variables (e.g., quantitative structure-activity relationships, QSARs), which must be calibrated with measured data, and are of dubious validity for extrapolation outside the training set data-space. Expanding or validating the scope of application of such QSARs requires more experimental data, which often ends up being the same data that the QSAR was supposed to serve to estimate.To overcome this combination of challenges, we will use a novel approach to QSAR development, where all of the calibration data (both target and descriptor variables) are calculated from molecular structure theory. Rates of the most likely breakdown pathways (target variables) will be calculated with the highest level of theoretical accuracy and these data will be correlated to molecular properties (descriptor variables) that are obtained with more computational methods that are more available and feasible for most chemists. Only after promising QSARs have been obtained by this approach will we attempt to validate them by predicting data for (safe and available) model compounds and comparison to measured experimental values.
The project is divided into four reaction pathways that contribute most to the overall fate of explosives in the environment: Hydrolysis and associated elimination reactions, which are ubiquitous in water; Homogeneous nitro reduction by outer-sphere electron transfer with dissolved electron donors; Heterogeneous nitro reduction by inner-sphere electron transfer at surfaces of reducing minerals; Polymerization of the amino products (with themselves and with the phenolic moieties associated with natural organic matter) of reduction, by oxidative coupling or nucleophilic condensation.
Each one of these will be investigated in five tasks: (i) reaction formulation and mining of existing data, (ii) calculation of target variable data with high level theory, (iii) calculation of descriptor variable data with lower level theory, (iv) correlation analysis and fitting QSARs, and (v) validation of data predicted with the QSAR.
The project should produce predictive models for the kinetics of the four most important processes that contribute to the fate of explosives in the environment. The models will be flexible enough to handle most types of molecular structures that are found in candidate compounds for new explosives. A more general benefit of this project we will to demonstrate a novel approach to chemical property estimation that could be applied to other environmental fate properties.
While this research is funded by the DoD's SERDP program, we need significant computational resources to do steps ii and iii. EMSL has the cutting edge computational resources that we can use to carry out this research.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2010-10-01
End Date
2012-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Salter-Blanc A, EJ Bylaska, H Johnston, and PG Tratnyek. 2015. "Predicting Reduction Rates of Energetic Nitroaromatic Compounds Using Calculated One-Electron Reduction Potentials." Environmental Science & Technology. doi:10.1021/es505092s
Salter-Blanc A, EJ Bylaska, JJ Ritchie, and PG Tratnyek. 2013. "Mechanisms and Kinetics of Alkaline Hydrolysis of the Energetic Nitroaromatic Compounds 2,4,6-Trinitrotoluene (TNT) and 2,4-Dinitroanisole (DNAN)." Environmental Science & Technology 47(13):6790-6798. doi:10.1021/es304461t