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Title (Primary) Quantitative structure-activity analysis of the algae toxicity of nitroaromatic compounds
Author Schmitt, H.; Altenburger, R.; Jastorff, B.; Schüürmann, G.;
Journal Chemical Research in Toxicology
Year 2000
Department OEC; BIOTOX; COE;
Volume 13
Issue 6
Language englisch;
Abstract Proliferation toxicity toward the algae Scenedesmus vacuolatus in a 24 h one-generation reproduction assay was determined for nitrobenzene and 18 derivatives, including two phenols. The resultant EC50 values covering more than 4 orders of magnitude were subjected to a quantitative structure−activity analysis (QSAR) using hydrophobicity in terms of the octanol/water partition coefficient in logarithmic form, log Kow, and 16 quantum chemical descriptors of molecular reactivity that were calculated with the AM1 scheme. For 13 mononitro derivatives and the highly hydrophobic trifluralin, a narcotic-type mode of action can explain most of the toxicity variation. Correction of log Kow for ionization for the phenols and quantification of the molecular susceptibility for one-electron reduction as apparently rate-determining biotransformation step by the energy of the lowest unoccupied molecular orbital, ELUMO, yields a highly significant QSAR for all 19 compounds (radj2 = 0.90), which can be further improved when adding the maximum net atomic charge at the nitro nitrogen, qnitro-N, as the third descriptor (radj2 = 0.93). Comparison of the energy of the singly occupied molecular orbital, ESOMO, of the radical anions as initial metabolites with the ESOMO of known redox cyclers suggests that dinitrobenzenes and TFM as well as multiply chlorinated nitrobenzenes may also exert oxidative stress. This is based on an ESOMO window of −0.30 to 0.55 eV as a tentative criterion for molecular structures to have the potential for redox cycling, derived from a set of eight known redox cyclers. The discussion includes a detailed analysis of apparently relevant metabolic pathways and associated modes of toxic action of nitroaromatics.
ID 7623
Persistent UFZ Identifier
Schmitt, H., Altenburger, R., Jastorff, B., Schüürmann, G. (2000):
Quantitative structure-activity analysis of the algae toxicity of nitroaromatic compounds
Chem. Res. Toxicol. 13 (6), 441 - 450