A DFT-based Quantum Theoretic QSAR Study of Nitrobenzenes' Toxicity to Tetrahymena Pyriformis

In this study, DFT-B3LYP level of theory with the 6-311G** basis set was used to calculate a set of molecular descriptors of 36 nitrobenzenes. Quantitative structure-activity relationship (QSAR) models of the toxicity (pIGC(50)) of 36 nitrobenzenes were established using some of the following calculated descriptors: HOMO energy (E-HOMO), LUMO energy (E-LUMO), the difference between LUMO and HOMO energy values (Delta E = E-LUMO-E-HOMO), average polarizability (P), dipole moment (mu), molecular volume (V) and the charge of nitro group (Q(-No2)). The QSAR models obtained by employing stepwise multiple regression techniques are aimed at correlating the structures with their reported experimental toxicity values. Among the models presented in this study, statistically the most significant one is a two-parameter linear equation with the correlation coefficient (R-2) of 0.896 and cross-validated correlation coefficient (R-CV(2)) of 0.878. To further validate the predictive ability of the resulting model, external validation was carried out with R-ext(2) and Q(ext)(2) values of 0.894, 0.900, 0.909, 0.874, 0.885 and 0.903, respectively. This study also reconstructed the obtained models using AMI-based calculated descriptors to demonstrate the superiority of DFT over AM1 for quantum calculations of mechanical descriptors. The results were discussed in the light of the main factors that influence the toxicity of nitrobenznenes.