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(83-15) QSARs for the prediction of the toxicity of poly-hydroxylated phenols to Tetrahymena pyriformis. Netzeva, Tatiana*,1,3, Aptula, Aynur2, Duffy, Judith1, Schultz, Terry4, Schüürmann, Gerrit2, Cronin, Mark1, 1 Liverpool John Moores University, Liverpool, England3 Medical University-Sofia, Sofia, Bulgaria2 UFZ Centre for Environmental Research, Leipzig, Germmany4 The University of Tennessee, Knoxville, TN ABSTRACT- The aim of this study was to develop quantitative structure-activity relationships for the toxicity to Tetrahymena pyriformis (IGC50) of 30 poly-hydroxylated phenols. These compounds included phenol 2-, 3- and 4- hydroxy substitued phenols. Physico-chemical descriptors for the expression of free radical formation, associated with the OH moiety on the aromatic ring, were calculated. These included one-electron equilibrium constants that did and did not account for the oxidation of the OH-group, homolytic bond dissociation energy (BDE), electronegativity (EN) and absolute hardness (AH), in addition to the distribution coefficient (log D) as a measure of hydrophobicity. The reactivity descriptors were calculated using the semi-empirical AM1 Hamiltonian in the MOPAC molecular orbital software. Following the removal of outliers, statistically significant two-parameter QSARs for toxicity were obtained by combination of log D with either BDE or AH [log (IGC50)-1 = 0.293 log D - 5.59 BDE + 82.5, n = 25, R2 = 0.804, R2CV = 0.724, s = 0.382, F = 45.1; log (IGC50)-1 = 0.552 log D - 3.70 AH + 16.5, n = 25, R2 = 0.870, R2CV = 0.836, s = 0.326, F = 73.4]. Many compounds exhibited toxicity greater than that associated with polar narcosis. Further, QSARs based on suggested that toxicity is associated with hydrophobicity and the probability of radical formation. [This work was supported in part by the European Union IMAGETOX Research Training Network (HPRN-CT- 1999-00015)]. Key words: QSAR, Tetrahymena pyriformis, free radicals, poly-hydroxylated phenols |
