Toxicity of polyhalogenated dibenzo-p-furans in the light of nucleic acid bases interaction

Abstract

Quantitative structure-activity relationship (QSAR) investigation utilizing quantum chemical descriptors under density functional theory is performed to predict the toxicity (pEC50) of a series of polyhalogenated dibenzo-p-furans (PHDFs). PHDFs are very important concern to the researchers due to their presence and diverse effects in the environment. A successful two parameter QSAR model is developed with a combination of a global descriptor known as charge transfer (ΔN) between toxins and biosystem and a local descriptor as Fukui function (fmax+) for maximum nucleophilic attack at the toxin site. A systematic analysis is performed to identify the electron donation/acceptance nature of the considered PHDF compounds with the choice of a model biosystems comprising five different nucleic acid bases, namely Adenine, Thymine, Guanine, Cytosine and Uracil to identify proper ΔN descriptor. Accordingly, PHDFs are found to be electron acceptors with maximum charge transfer from Guanine and therefore, ΔNG is utilized as the charge transfer parameter for all the toxins in the present work. The selected combination of global and local descriptors (ΔNG andfmax+) are found to predict 93% of the observed toxicity (pEC50) of the PHDFs. The developed QSAR model is tested for two different test sets: PHDFs and polyhalogenated biphenyls (PHBs) with about 90% of prediction of their toxicity values, which confirms the importance of the selected descriptors.