Development of ecotoxicity QSAR models based on partial charge descriptors for acrylate and related compounds

Abstract

Using Gasteiger's partial equalization of orbital electronegativity (PEOE) method, we constructed ecotoxicity prediction equations based on two-dimensional descriptors for α,β-unsaturated carbonyl compounds. After examining electrostatic effects on the calculated ecotoxicities of 10 α,β-unsaturated ketones and aldehydes (A-group compounds) by using the Mulliken atomic charges on the carbonyl oxygen atoms, we investigated the efficacy of the PEOE descriptors for the same 10 compounds and the correlation between the PEOE descriptors and the Mulliken charge. We then constructed QSAR models for acute fish and Daphnia toxicities by using the PEOE descriptors for acrylic acids and compounds with acrylate-like substructures (CH-group compounds). In the constructed models, the adjusted squared correlation coefficients between measured and calculated toxicities with the lowest Akaike information criterion were 0.77 and 0.79, respectively. The applicability of the constructed models was then evaluated for various methacrylates and similar compounds (CH₃-group compounds). Both the fish and the Daphnia toxicities of some of the CH₃-group compounds were underestimated by these models. Nevertheless, we concluded that the QSAR models based on the PEOE descriptors were practical for predicting acute toxicity, especially for α,β-unsaturated carbonyl compounds with an α-hydrogen. Combining hydrophobicity and PEOE descriptors led to accurate predictions for fish toxicity.

Keywords:

• ecotoxicity predictions
• partial charges
• PEOE
• α,β-unsaturated carbonyl compounds
• acrylate, acute fish and Daphnia toxicities