Structural Chemistry

, Volume 27, Issue 1, pp 191–198 | Cite as

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

  • Oleg V. Tinkov
  • Luidmila N. Ognichenko
  • Victor E. Kuz’min
  • Leonid G. Gorb
  • Anna P. Kosinskaya
  • Nail N. Muratov
  • Eugene N. Muratov
  • Frances C. Hill
  • Jerzy Leszczynski
Original Research


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.


Nitroaromatic xenobiotics Acute toxicity SiRMS Virtual screening 



We thank ERDC for financial support (grant number W912HZ-13-P-0037). The computation time was provided by the Extreme Science and Engineering Discovery Environment (XSEDE) by National Science Foundation Grant Number OCI-1053575 and XSEDE award allocation Number DMR110088 and by the Mississippi Center for Supercomputer Research. EM is grateful for financial support from the US National Institutes of Health (GM 096967 and GM66940). The use of trade, product or firm names in this report is for descriptive purposes only and does not imply endorsement by the US Government. Results in this study were funded and obtained from research conducted under the Environmental Quality Technology Program of the United States Army Corps of Engineers by the US Army ERDC. Permission was granted by the Chief of Engineers to publish this information. 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.

Supplementary material

11224_2015_715_MOESM1_ESM.xls (842 kb)
Supplementary material 1 (XLS 842 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Oleg V. Tinkov
    • 1
  • Luidmila N. Ognichenko
    • 2
  • Victor E. Kuz’min
    • 2
  • Leonid G. Gorb
    • 3
  • Anna P. Kosinskaya
    • 2
    • 4
  • Nail N. Muratov
    • 5
  • Eugene N. Muratov
    • 6
  • Frances C. Hill
    • 7
  • Jerzy Leszczynski
    • 8
  1. 1.Department of ChemistryT.G. Shevchenko State UniversityTiraspolMoldova
  2. 2.Department of Molecular Structures and ChemoinformaticsA.V. Bogatsky Physical–Chemical Institute NAS of UkraineOdessaUkraine
  3. 3.HX5, LLCVicksburgUSA
  4. 4.Odessa National Medical UniversityOdessaUkraine
  5. 5.Chemical-Technological DepartmentOdessa National Polytechnic UniversityOdessaUkraine
  6. 6.Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of PharmacyUniversity of North CarolinaChapel HillUSA
  7. 7.US Army Research and Development CenterVicksburgUSA
  8. 8.Department of Civil and Environmental Engineering, Interdisciplinary Nanotoxicity CenterJackson State UniversityJacksonUSA

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