Exploring Predictive QSAR Models Using Quantum Topological Molecular Similarity (QTMS) Descriptors for Toxicity of Nitroaromatics to Saccharomyces cerevisiae

Abstract

In view of the widespread industrial use of nitroaromatics and their consequent ecotoxicological hazard potential, we constructed predictive Quantitative Structure -Activity Relationship (QSAR) models for the toxicity of nitroaromatics to the ecologically important species Saccharomyces cerevisiae. We used Quantum Topological Molecular Similarity (QTMS) descriptors along with electrophilicity index (E LUMO ) and lipid water partition coefficient (log K ow ) as predictor variables. The QTMS descriptors were calculated at B3LYP/6-311 þ G(2d,p) level of theory. QTMS descriptors were employed to complement the deficiency of E LUMO in setting up predictive QSAR models from the view point of external validation. The dataset was divided into a training set (18 compounds) and test set (six compounds) in a ratio of three to one. Partial Least Square (PLS) models were developed based on the training set compounds. The predictive capacity of the models was assessed by the test compounds. The models were also validated by a randomisation test and leave-one-seventh-out crossvalidation test. The results suggest that Bond Critical Point (BCP) descriptors can develop predictive QSAR models for nitroaromatic toxicity to Saccharomyces cerevisiae when used along with E LUMO and log K ow . The diagnostic potential of QTMS descriptors could also reveal the importance of the nitro group for nitroaromatic toxicity.

Chemical Information and Descriptors

“…Seven types of descriptors (ρ, r 2 ρ, λ, ε, K, G, and equilibrium bond lengths) can be calculated for each of the bonds connecting the adjacent common atoms [40,41]. The electron density at a BCP, denoted by ρ b , can be related to bond order via an exponential relationship.…”

Applications of Density Functional Theory to Biological and Bioinorganic Chemistry

“…Latosińska [233,234] delineates the application of nuclear quadrupole resonance (NQR) spectroscopy in studying drug molecules. The variable selection and modeling method based on the prediction (VSMP) [238], quantitative structure-(chromatographic) retention relationships (QSRR) [239], topological quantum similarity index (TQSI) [240,241] models, and quantum topological molecular similarity (QTMS) descriptors [242,243] also have ample contributions towards ensuring refinements in the predictive nature of quantitative structure-activity relationships. The variable selection and modeling method based on the prediction (VSMP) [238], quantitative structure-(chromatographic) retention relationships (QSRR) [239], topological quantum similarity index (TQSI) [240,241] models, and quantum topological molecular similarity (QTMS) descriptors [242,243] also have ample contributions towards ensuring refinements in the predictive nature of quantitative structure-activity relationships.…”

“…The cDFT formalism of Dederich et al and Wu et al has been employed by various groups to model the two diabatic states and to compute the terms entering the adiabatic and nonadiabatic rate constant expressions [241][242][243][244]. The cDFT formalism of Dederich et al and Wu et al has been employed by various groups to model the two diabatic states and to compute the terms entering the adiabatic and nonadiabatic rate constant expressions [241][242][243][244].…”

QSTR with extended topochemical atom (ETA) indices. 14. QSAR modeling of toxicity of aromatic aldehydes to Tetrahymena pyriformis

“…Internal validation parameters (Q 2 , r 2 m(LOO) [67] and rmsep int [68]), external validation parameters (Q 2 ext(F1) , Q 2 ext(F2) [69,70] and Q 2 ext(F3) [71], r 2 m(test) [72] and rmsep ext [68]) and overall validation parameter [r 2 m(overall) ] [70] were also reported. The r 2 m metrics have been recently introduced by the present authors' group [67,72] and extensively used by them [73][74][75][76][77] and also other research groups [78][79][80][81][82]. We have also performed process randomization test for the genetic models [83] and reported the c R 2 p values [84].…”