Netzeva, T.I.; Schultz, T.W. QSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data. Chemosphere 2005, 61, 11, 1632–1643.

Abstract

The aim of the study was to develop quantitative structure-activity relationships (QSARs) for a large group of 77 aromatic aldehydes tested for acute toxicity to the ciliate Tetrahymena pyriformis using mechanistically interpretable descriptors. The resulting QSARs revealed that the 1-octanol/water partition coefficient (log K(ow)), is the most important descriptor of aldehyde aquatic toxic potency. The model with log K(ow) was improved by adding electronic descriptor (the maximum acceptor superdelocalizability in a molecule--A(max)) based on calculations with the semi-empirical AM1 model. The two descriptors reflect the two main processes responsible for demonstration of acute aquatic toxicity, namely penetration through cell membranes (log K(ow)) and interaction with the biomacromolecules (A(max)) into the cells. Results showed that generally the studied group of aldehydes could be modeled by this simple two-descriptor approach. However, the group of 2- and/or 4-hydroxylated aldehydes demonstrates enhanced toxicity compared to the other aldehydes. Transformation to quinone-like structures is proposed as the explanation for this enhanced potency. The 2- and/or 4-hydroxylated aldehydes are modeled successfully by [log(1/IGC50) = 0.540(0.038) log K(ow) + 8.30(2.88)A(max) - 3.11(0.92), n = 25, R2 = 0.916, R(CV)2 = 0.896, s = 0.141, F = 120], while the other aldehydes are modeled by the relationship [log(1/IGC50) = 0.583 (0.034)log K(ow) + 9.80(2.62)A(max) - 4.04 (0.85), n = 52, R2 = 0.864, R(CV)2 = 0.844, s = 0.203, F = 156], which is similar to the general benzene model.