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Nitrobenzene toxicity: QSAR correlations and mechanistic interpretations
Author(s) -
Katritzky Alan R.,
Oliferenko Polina,
Oliferenko Alexander,
Lomaka Andre,
Karelson Mati
Publication year - 2003
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.643
Subject(s) - chemistry , nitrobenzene , tetrahymena pyriformis , quantitative structure–activity relationship , electrophile , picric acid , nitro , computational chemistry , stereochemistry , acute toxicity , nucleophile , ionization energy , medicinal chemistry , toxicity , ionization , organic chemistry , biochemistry , ion , alkyl , tetrahymena , catalysis
The overall five‐parameter QSAR correlation [ $R^2=0.723, R_{\rm cv}^2=0.676, s=0.42$ in terms of log(IGC 50 −1 )] based on CODESSA‐PRO methodology for the aquatic toxicity of 97 substituted nitrobenzenes to the ciliate Tetrahymena pyriformis supports previous conclusions that hydrophobicity and electrophilic reactivity control nitrobenzene toxicity. Correcting for the ionization of acidic species (picric and nitrobenzoic acids) improves the results: $R^2=0.813, R_{\rm cv}^2=0.787, s=0.346$ . Consideration of the total set of 97 compounds suggests two mechanisms of toxic action. A subset containing 43 compounds favorably disposed to reversible reduction of nitro group with respect to the single occupied molecular orbital energy, E SOMO correlated well with just four theoretically derived descriptors: $R^2=0.915, R_{\rm cv}^2=0.890, s=0.276$ . Another set of 49 substances predisposed to aromatic nucleophilic substitution modeled well ( $R^2=0.915, R_{\rm cv}^2=0.888, s=0.232$ ) with five descriptors. Copyright © 2003 John Wiley & Sons, Ltd.