A DFT-based toxicity QSAR study of aromatic hydrocarbons to Vibrio fischeri: Consideration of aqueous freely dissolved concentration

In the present study, quantitative structure-activity relationship (QSAR) techniques based on toxicity mechanism and density functional theory (DFT) descriptors were adopted to develop predictive models for the toxicity of alkylated and parent aromatic hydrocarbons to Vibrio fischeri. The acute toxicity data of 17 aromatic hydrocarbons from both literature and our experimental results were used to construct QSAR models by partial least squares (PLS) analysis. With consideration of the toxicity process, the partition of aromatic hydrocarbons between water phase and lipid phase and their interaction with the target biomolecule, the optimal QSAR model was obtained by introducing aqueous freely dissolved concentration. The high statistical values of R-2 (0.956) and Q(CuM)(2) (0.942) indicated that the model has good goodness-of-fit, robustness and internal predictive power. The average molecular polarizability (alpha) and several selected thermodynamic parameters reflecting the intermolecular interactions played important roles in the partition of aromatic hydrocarbons between the water phase and biomembrane. Energy of the highest occupied molecular orbital (E-HOMO) was the most influential descriptor which dominated the toxicity of aromatic hydrocarbons through the electron-transfer reaction with biomolecules. The results demonstrated that the adoption of freely dissolved concentration instead of nominal concentration was a beneficial attempt for toxicity QSAR modeling of hydrophobic organic chemicals. (C) 2016 Elsevier B.V. All rights reserved.