DFT study on the structure-toxicity relationship of dioxin compounds using PLS analysis

Density functional theory (DFT) at B3LYP/6-311G** level was employed to optimise the dioxin compounds, i.e., 25 polychlorinated or brominated dibenzo-p-dioxins (PCDDs or PBDDs) and 34 polychlorinated dibenzofurans (PCDFs) involved in this investigation. Three groups of descriptors mainly related to chemical reactivity, molecular overall charge distribution and thermochemical property were calculated. With partial least squares (PLS) analysis and variable importance in the projection (VIP), the least significant descriptors were removed from the quantitative structure-activity relationship (QSAR), which was focused on exploring the influential factors responsible for the variance of binding affinities of dioxins to aryl hydrocarbon receptor (AhR). With better-improved and predictive QSAR (Q(2)(cum) = 0.827), further understanding of the nature of toxicity was available. Both dispersion interaction and electrostatic interaction were considered to be important and together capable of accounting for the most part of the total binding affinities, though the former could make more contribution than the latter. Comparatively, the long-range dispersion interaction should be very small.