Quantitative structure-activity analysis of the algae toxicity of nitroaromatic compounds

Proliferation toxicity toward the algae Scenedesmus vacuolatus in a 24 h on e-generation reproduction assay was determined for nitrobenzene and 18 deri vatives, including two phenols. The resultant EC50 values covering more tha n 4 orders of magnitude were subjected to a quantitative structure-activity analysis (QSAR) using hydrophobicity in terms of the octanol/water partiti on coefficient in logarithmic form, log K-ow, and 16 quantum chemical descr iptors of molecular reactivity that were calculated with the AM1 scheme. Fo r 13 mononitro derivatives and the highly hydrophobic trifluralin, a narcot ic-type mode of action can explain most of the toxicity variation. Correcti on of log K-ow for ionization for the phenols and quantification of the mol ecular susceptibility for one-electron reduction as apparently rate-determi ning biotransformation step by the energy of the lowest unoccupied molecula r orbital, E-LUMO, yields a highly significant QSAR for all 19 compounds (r (adj)(2) = 0.90), which can be further improved when adding the maximum net atomic charge at the nitro nitrogen, q(nitro-N), as the third descriptor ( r(adj)(2) = 0.93). Comparison of the energy of the singly occupied molecula r orbital, E-SOMO, of the radical anions as initial metabolites with the E- SOMO of known redox cyclers suggests that dinitrobenzenes and TFM as well a s multiply chlorinated nitrobenzenes may also exert oxidative stress. This is based on an E-SOMO window of -0.30 to 0.55 eV as a tentative criterion f or molecular structures to have the potential for redox cycling, derived fr om a set of eight known redox cyclers. The discussion includes a detailed a nalysis of apparently relevant metabolic pathways and associated modes of t oxic action of nitroaromatics.