Modeling and prediction by using whim descriptors in QSAR studies: toxicity of heterogeneous chemicals on Daphnia magna

Abstract

Recently proposed 3-dimensional molecular indices (WHIM: Weighted Holistic Invariant Molecular descriptors), developed to describe the whole molecular structure in terms of size, shape, symmetry and atom distribution, are applied in QSARs for the toxicity of several groups of organic chemicals to Daphnia magna. Models with excellent predictive capability have been obtained for amines, chlorobenzenes, organotin compounds and organophosphorous pesticides. Moreover, a more general model has been produced for the whole, highly heterogeneous, set of 49 compounds. The resulting 7-variable equation accounts for 75% of the variability of the toxic effect, over a range of more than 7 logarithmic units, and the model has been externally validated with success. Some attempts are made here to interpret the toxicological mode of action of the chemicals in function of molecular features described by the indices.