QSPR prediction of impact sensitivity of nitro energetic compounds
Résumé
The new European regulation of chemicals REACH aiming to reinforce the control of risks from chemicals in Europe entered into force in 2007. It may require the reassessment of hazardous properties for up to 140000 substances. However, the complete experimental characterization of (eco) toxicological and physico-chemical properties is time-consuming, costly and sometimes not feasible at the R&D stage. Therefore, the development of validated alternative methods for assessing hazardous properties of chemicals is promoted in REACH. Quantitative Structure-Property Relationships (QSPR), already used extensively in biological and toxicological applications to reduce unnecessary animal testing, are now also developed to predict physico-chemical properties. The present work focuses on the development and validation of QSPR models to predict the impact sensitivity of potentially explosive molecules (nitroaromatics, nitroaliphatics and nitramines, ...).To set up appropriate relationships between different molecular descriptors of these compounds and their impact sensitivity, an original approach associating the QSPR method to quantum chemical calculations was developed. More than 300 molecular descriptors (constitutional, topological, geometrical, quantum chemical) were calculated using CodessaPro software from calculated molecular structures, optimized with the Density Functional Theory (DFT) in GaussianO3 package. These descriptors were integrated into statistical multilinear regressions to link them quantitatively to the experimental impact sensitivity property. Projection and classification methods (PCA, PLS, decision trees) were also used, notably for the development of qualitative models. When enough experimental data became available, models were developed on a training dataset and were validated according to the OECD principles for the use ofQSPRs in a regulatory context. Once validated, models are expected to be integrated into a global tool to estimate explosibility hazards of substances (for classification purposes) and the need for further experimental testing