No abstract

Quantitative structure-activity relationship analysis and estimation of toxicological effects at lower-mid trophic levels provide first aid means to understand the toxicity of chemicals. Daphnia magna serves as a good starting point for such toxicity studies and is also recognized for regulatory use in estimating the risk of chemicals. The ECOTOX database was queried and analysed for available data and a homogenous subset of 253 compounds for the endpoint LC50 48 h was established. A four-parameter quantitative structure-activity relationship was derived (coefficient of determination, r (2) = 0.740) for half of the compounds and internally validated (leave-one-out cross-validated coefficient of determination, [Formula: see text] = 0.714; leave-many-out coefficient of determination, [Formula: see text] = 0.738). External validation was carried out with the remaining half of the compounds (coefficient of determination for external validation, [Formula: see text] = 0.634). Two of the descriptors in the model (log P, average bonding information content) capture the structural characteristics describing penetration through bio-membranes. Another two descriptors (energy of highest occupied molecular orbital, weighted partial negative surface area) capture the electronic structural characteristics describing the interaction between the chemical and its hypothetic target in the cell. The applicability domain was subsequently analysed and discussed.

No abstract

This chapter presents a review of whole-molecule descriptors obtained from two-dimensional chemical structure. The sections include a short overview of the mathematical foundation (graph theory) that is behind the calculation of topological descriptors. A concise overview, together with practical calculated examples, is provided for major classes of 2-D descriptors, including topological indices, information content descriptors, electrotopological descriptors, and autocorrelation descriptors. Numerous examples of their practical use in QSAR modelling are presented. The examples are dedicated to in silico toxicology modelling applications, including toxicities towards Pimephales promelas, Tetrahymena pyriformis, Daphnia magna, Vibrio fischeri, Chlorella vulgaris, rodents and humans. Also the role of 2-D descriptors in the modelling of soil sorption coefficients is presented. Emphasis is given to the interpretation of topological descriptors in QSAR models. Finally, a state-of-the art overview of available applications for the calculation of molecular descriptors is given together with an extensive bibliography of the relevant literature.

The abstraction of hydrogen by general radicals has a wide role in environmental and also in technological processes because it results in reactive free radicals that play a vital role in atmospheric chemistry and also in biochemical processes. In addition to experimental studies, the theoretical modelling of this elementary reaction has been important for understanding and predicting respective rate constants. In this paper, molecular descriptors in the context of a QSAR approach are used to codify the relationship between molecular structure and rate constants. Unique experimental data is collected from the literature for the reaction R(i)• + R(j)H → R(i)H + R(j)•, where R(i)• = H• and R(j)• are diverse radicals. The four-parameter QSAR model (n = 34, r(2) = 0.81, r(2)(CV) = 0.74, r(2)(scr) = 0.12, s(2) = 0.19) is presented for the bimolecular rate constants, accompanied with model diagnostics and analysis of descriptors in the model.