Density functional theory-based reactivity descriptors for dioxins

Reactivity descriptors based on density functional theory were used to analyse the toxicities and to predict the reactive sites of various dioxins at the B3LYP/6-311G(d,p) level. Many polychlorinated dibenzo-p-dioxins, including 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD), 2,3,7,8-tetrafluoro dibenzo-p-dioxin (TFDD) and 2,3,7,8-tetrabromo dibenzo-p-dioxin (TBDD), were considered for this purpose. The present study showed that higher toxicity dioxins had a large atomic charge in their lateral part. The global softness values for the more toxic dioxins were larger than those of the less toxic dioxins and, thus, the former should be more polarizable than their less toxic counterparts. Local softness values revealed that chlorine atomic sites in the toxic dioxins had the highest electrophilicity and these sites may initiate the interaction with aromatic hydrocarbon (Ah) receptors. Interaction between dioxin and Ah receptors was studied by considering three amino acids. Reactivity descriptors for the three selected amino acids were obtained to determine the most probable sites of their interactions with the dioxins. The results revealed that dioxins were electron acceptors in their interactions with receptors. The 2,3,7,8-TFDD may be less toxic, while its brominated counterpart is at least as toxic as 2,3,7,8-TCDD.