QSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data

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/IGC 50) = 0.540(0.038) log K ow + 8.30(2.88) A max − 3.11(0.92), n = 25, R 2 = 0.916, R CV 2 = 0 . 896 , s = 0.141, F = 120], while the other aldehydes are modeled by the relationship [log(1/IGC 50) = 0.583 (0.034)log K ow + 9.80(2.62) A max − 4.04 (0.85), n = 52, R 2 = 0.864, R CV 2 = 0 . 844 , s = 0.203, F = 156], which is similar to the general benzene model.