Toxicity prediction of PHDDs and phenols in the light of nucleic acid bases and DNA base pair interaction.

Abstract The applicability of Density Functional Theory (DFT) based descriptors for the development of quantitative structure-toxicity relationships (QSTR) is assessed for two different series of toxic aromatic compounds, viz., polyhalogenated dibenzo- p -dioxins (PHDDs) and phenols (PHs). A series of 20 compounds each for PHDDs and PHs with their experimental toxicities (IC 50 and IGC 50 ) is chosen in the present study to develop DFT based efficient quantum chemical parameters (QCPs) for explaining the toxin potential of the considered compounds. A systematic analysis to find out the electron donation/acceptance nature of these selected compounds with the considered model biosystems, viz., nucleic acid (NA) bases and DNA base pairs, is performed to identify potential QCPs. Accordingly, PHDDs is found to be electron acceptors whereas phenols as donors, during their interaction with biosystems. Two parameter regression model is carried out comprising global charge transfer (Δ N ), and local Fukui Function’s for nucleophilic attack ( f k + ) for PHDDs and the same for electrophilic attack ( f k − ) in case of PHs. It is heartening to note that our chosen descriptors, viz, charge transfer (Δ N ) and Fukui Function ( f k ± ) plays a crucial role by explaining more than 90% of the observed toxic behavior (in terms of correlation-coefficient, R ) of PHDDs and PHs. The developed QCPs, viz., Δ N and f k ± can be added as the new descriptors in the QSTR parlance.