Computational assessment of environmental hazards of nitroaromatic compounds: influence of the type and position of aromatic ring substituents on toxicity

This study summarizes the results of our recent QSAR and QSPR investigations on prediction of numerous aspects of environmental behavior of nitro compounds. In this study, we applied the QSAR/QSPR models previously developed by our group for virtual screening of energetic compounds, their precursors and other compounds containing nitro groups. To make predictions on the environmental impact of nitro compounds, we analyzed the trends in the change of the experimentally obtained and QSAR/QSPR-predicted values of aqueous solubility, lipophilicity, Ames mutagenicity, bioavailability, blood–brain barrier penetration, aquatic toxicity on T. pyriformis and acute oral toxicity on rats as a function of chemical structure of nitro compounds. All the models were developed using simplex descriptors in combination with random forest (RF) modeling techniques. We interpreted the possible environmental impact (different toxicological properties) in terms of dividing considered nitro compounds based on hydrophobic and hydrophilic characteristics and in terms of the influence of their molecular fragments that promote and interfere with toxicity. In particular, we found that, in general, the presence of amide or tertiary amine groups leads to an increase in toxicity. Also, it was predicted that compounds containing a NO2 group in the para-position of a benzene ring are more toxic than meta-isomers, which, in turn, are more toxic than ortho-isomers. In general, we concluded that hydrophobic nitroaromatic compounds, especially the ones with electron-accepting substituents, halogens and amino groups, are the most environmentally hazardous