Toxicity analysis of benzidine through chemical reactivity and selectivity profiles: a DFT approach (original) (raw)
Related papers
2010
In the present study, the density functional B3LYP/6-311G** level of theory was used to compute and map the molecular surface electrostatic potentials of a group of substituted nitrobenzenes to identify common features related to their subsequent toxicities. Several statistical properties including potentials’ extrema (Vmin, Vmax), molecular volume, surface area, polar surface area, along with different energies were computed. A little linear correlation was revealed between Vmin and surface area, and systems’ toxicities. Another computations employed quantitative structure– property relationships model in CODESSA package to correlate toxicities with calculated descriptors. Statistically, the most significant correlation is a five-parameter equation with correlation coefficient, R values of 0.962, and the cross-validated correlation coefficient, RCV=0.950. The obtained models allowed us to reveal toxic activity of nitrobenzenes.
Mutagenicity Studies of Benzidine and Its Analogs: Structure-Activity Relationships
Toxicological Sciences, 2000
The Ames Salmonella/microsome assay was employed to test the mutagenicity of benzidine and its analogs using strains TA98 and TA100 in the presence and absence of Aroclor 1254-induced rat S9 mix. 3,3-Dichlorobenzidine-2HCl and 4,4-dinitro-2-biphenylamine were directly mutagenic to TA98, while 4,4-dinitro-2biphenylamine was directly mutagenic to both TA98 and TA100 in the absence of S9 mix. 2-Aminobiphenyl, 3-aminobiphenyl, and 3,3-5,5-tetramethylbenzidine were not mutagenic in either strains in the presence or absence of S9. In the presence of S9 mix, 4-aminobiphenyl, benzidine, 3,3-dichlorobenzidine-2HCl, 3,3-dimethoxybenzidine, 3,3-4,4-tetraaminobiphenyl, o-tolidine, N, N-N, N-tetramethylbenzidine, and 4,4-dinitro-2-biphenylamine were mutagenic to TA98; 4-aminobiphenyl, 3,3-dichlorobenzidine-2HCl, 3,3-dimethoxybenzidine, and 4,4-dinitro-2-biphenylamine were mutagenic to TA100. Physicochemical parameters of these compounds including oxidation potentials, the energy difference between the lowest unoccupied molecular orbital and the highest occupied molecular orbital, ionization potentials, dipole moment, relative partition coefficient, and basicity did not correlate with their bacterial mutagenic activities.
A conceptual DFT approach towards analysing toxicity
2005
The applicability of DFT-based descriptors for the development of toxicological structureactivity relationships is assessed. Emphasis in the present study is on the quality of DFT-based descriptors for the development of toxicological QSARs and, more specifically, on the potential of the electrophilicity concept in predicting toxicity of benzidine derivatives and the series of polyaromatic hydrocarbons (PAH) expressed in terms of their biological activity data (pIC 50). First, two benzidine derivatives, which act as electron-donating agents in their interactions with biomolecules are considered. Overall toxicity in general and the most probable site of reactivity in particular are effectively described by the global and local electrophilicity parameters respectively. Interaction of two benzidine derivatives with nucleic acid (NA) bases/selected base pairs is determined using Parr's charge transfer formula. The experimental biological activity data (pIC 50) for the family of PAH, namely polychlorinated dibenzofurans (PCDF), polyhalogenated dibenzo-p-dioxins (PHDD) and polychlorinated biphenyls (PCB) are taken as dependent variables and the HF energy (E), along with DFT-based global and local descriptors, viz., electrophilicity index (ω) and local electrophilic power (ω +) respectively are taken as independent variables. Fairly good correlation is obtained showing the significance of the selected descriptors in the QSAR on toxins that act as electron acceptors in the presence of biomolecules. Effects of population analysis schemes in the calculation of Fukui functions as well as that of solvation are probed. Similarly, some electron-donor aliphatic amines are studied in the present work. We see that global and local electrophilicities along with the HF energy are adequate in explaining the toxicity of several substances, both electron donors or acceptors when they interact with biosystems, in gas as well as solution phases.
Journal of Physical Organic Chemistry, 2014
A number of hybrid exchange-correlation functionals, namely, B3LYP, BMK, M06-2X, PBE0, CAM-B3LYP, BH&HLYP, and HSE06, have been employed to calculate the electronic spectra of a series of the N,N′-derivatives of benzidine, their radical cations, and dications; the results are compared with available experimental data. In most cases studied, the timedependent density functional theory results based on the CAM-B3LYP and BMK functionals indicate a better agreement with the experimental absorption bands in the UV-Vis spectra. The other five functionals provide statistically comparable but lower accuracy. On the basis of the time-dependent density functional theory calculations with both the CAM-B3LYP and BMK functionals and the 6-311 + G(d,p) basis set including effect of polar medium simulation, the electronic spectrum of the benzidine dication has been completely assigned. Because the latter dication is formed during oxidative coupling of two aniline molecules, as the reductive reagents for analytical determination of strong oxidants, the mechanism of this reaction has been clarified on the ground of density functional theory calculations including effect of dispersion for all possible reaction paths and intermediates. By the analysis of spectral properties and ionization energies of several aniline derivatives, a few simple electronic descriptors that help to justify a reagent molecule as a potentially favorable for colorimetric use have been proposed.
Toxicological Sciences, 2003
) were examined for DNA damage in human lymphocytes using the alkaline comet assay. All the tested compounds showed a distinct disparity in their respective DNA-damaging capacities with an order of DABZ > BZ > DCBZ > 2-ABP > DEBZ > 4-ABP > DMBZ when lymphocytes were exposed to these chemicals for 2 h. Results show that the DNA-damaging effects of these compounds had no bearing on some physicochemical parameters including oxidation potentials, the energy differences between the lowest unoccupied molecular orbital and the highest occupied molecular orbital, ionization potentials, dipole moment, and relative partition coefficient. On the other hand, the free radical scavengers, including catalase, SOD, BHT, EDTA, and histidine exerted varying degrees of inhibitory effects on the DNA damage caused by benzidine. This suggests that genotoxicity in lymphocytes caused by benzidine proceeded via a reactive oxygen species (ROS)-mediated mechanism.
The Use of the Density Threshold Value as a Shape Descriptor on the Toxicity of Benzene Derivatives
The Use of the Density Threshold Value as a Shape Descriptor on the Toxicity of Benzene Derivatives, 2016
The Quantitative Structure Activity Relationship (QSAR) method, based on the three-dimensional (3D) shapes of formal molecular bodies and computed molecular descriptors, was used to calculate the octanol-water partition coefficient (logKow) of benzene derivatives to indicate their toxicity. The aim of this study is to use electron density threshold values as descriptors in predicting toxicology of benzene derivatives. Through Density Domain Analysis (DDA), a shape fragment database of benzene derivatives was constructed. Electron density threshold values were generated from molecular isodensity counter surfaces (MIDCO) of benzene molecules that were calculated at the ab initio HF/6-31G* level. Multiple linear regression analyses were performed, and two successful QSAR models were obtained. The analysis of variance (ANOVA) ratio for regression (F) and the significance of F (Fs) values was also used to evaluate the predictive power of the established QSAR models. The results indicate that the electron density threshold value, "a", gives a specific description of the 3D shape of electron density clouds. These models were further analyzed by three 3D shape features as one local and two global descriptors based on the electron density threshold "a" value. The global and local properties of benzene derivatives were found to exhibit similar toxicity behaviors.
Determinants of Molecular Reactivity as Criteria for Predicting Toxicity: Problems and Approaches
Environmental Health Perspectives, 1985
We discuss the physicochemical basis for mechanisms of action of toxic chemicals and theoretical methods that can be used to understand the relation to the structure of these chemicals. Molecular properties that determine the chemical reactivity of the compounds are proposed as parameters in the analysis of such structure-activity relationships and as criteria for predicting potential toxicity. The theoretical approaches include quantitative methods for structural superposition of molecules and for superposition of their reactivity characteristics. Applications to polychlorinated hydrocarbons are used to illustrate both rigid superposition methods, and methods that take advantage of structural flexibility. These approaches and their results are discussed and compared with methods that afford quantitative structural comparisons without direct superposition, with special emphasis on the need for efficient automated methods suitable for rapid scans of large structural data bases. Quantum mechanical methods for the calculation of molecular properties that can serve as reactivity criteria are presented and illustrated. Special attention is given to the electrostatic properties of the molecules such as the molecular electrostatic potential, the electric fields, and the polarizability terms calculated from perturbation expansions. The practical considerations related to the rapid calculation of these properties on relevant molecular surfaces (e.g., solventor reagent-accessible surfaces) are discussed and exemplified, stressing the special problems posed by the structural variety of toxic substances and the paucity of information on their mechanisms of action. The discussion leads to a rationale for the use of the combination of theoretical methods to reveal discriminant criteria for toxicity and to analyze the initial steps in the metabolic processes that could yield toxic products.
Structure and vibrational spectra of benzidine
Journal of Molecular Structure, 2003
The geometry and vibrational spectrum of benzidine have been computed by ab initio calculations using the DFT/B3LYP method with 6-31 þ G(d,p) basis set. In the most stable geometry, the dihedral angle between the two phenyl rings was found to be around 388. Calculated wavenumbers were scaled by a single factor 0.965 to approximately correct for vibrational anharmonicity as well as for overestimation of the force constants. Normal coordinate analysis of benzidine and some of its deuterated derivatives have also been performed in valance force field approximation in order to demonstrate the transferability of the force field of aniline. Good agreements between the two different calculation results (ab initio and force field refinement methods) and between the calculated and observed values are found. q
The journal of physical chemistry. A, 2014
Structural, topological, optical, energetic, and magnetic properties and reactivity parameters of benzidine, its radical cation, and its dication as well as molecular complexes of the benzidine dication with the F(-), Cl(-), Br(-), I(-), NO3(-), HSO4(-), and H2PO4(-) anions were calculated at the B3LYP/6-311++G(2d,2p) level of theory in the CH2Cl2 medium. The CAM-B3LYP functional (as the most reliable one) and the 6-311++G(3df,3pd) basis set were used for the UV-vis absorption spectra prediction. The obtained spectral results are in a good agreement with available experimental data. A number of the calculated global and local molecular properties, including several recently developed ones, (in general, more than 20 parameters), namely, λmax, the bond lengths and orders (l and LA,B), adiabatic ionization energy (IEad), global electrophilicity index (ω), condensed electrophilic Fukui functions (f(+)) and dual descriptor (ΔfA), van der Waals molecular volume, nuclear independent chemic...