A quantum chemical based toxicity study of estimated reduction potential and hydrophobicity in series of nitroaromatic compounds

Abstract

Nitroaromatic compounds and the products of their degradation are toxic to bacteria, cells and animals. Various studies have been carried out to better understand the mechanism of toxicity of aromatic nitrocompounds and their relationship to humans and the environment. Recent data relate cytotoxicity of nitroaromatic compounds to their single- or two-electron enzymatic reduction. However, mechanisms of animal toxicity could be more complex. This work investigates the estimated reduction and oxidation potentials of 34 nitroaromatic compounds using quantum chemical approaches. All geometries were optimized with density functional theory (DFT) using the solvation model based on density (SMD) and polarizable continuum model (PCM) solvent model protocols. Quantitative structure-activity/property (QSAR/QSPR) models were developed using descriptors obtained from quantum chemical optimizations as well as the DRAGON software program. The QSAR/QSPR equations developed consist of two to four descriptors. Correlations have been identified between electron affinity (E) and hydrophobicity (log P).

Electrochemical investigations of DNA-Intercalation potency of bisnitrophenoxy compounds with different alkyl chain lengths

“…Nitroaromatic compounds have been found to be biologically active and possess antitumor, antimicrobial, antibiotics and anticancer nature [15,16,17,18,19]. These tremendous activities of nitroaromatic compounds are due to the cytotoxic activity of the radical anions, generated during the metabolic pathways of nitroaromatic compounds [20,21].…”

The QSAR study for antibacterial activity of structurally diverse nitroaromatics

“…The (cyto)toxicity of nitroaromatics against mammalian cells was often observed to increase with an increase in their electron-accepting potency (expressed in terms of the experimentally measured single-electron reduction potentials (E 1 7 ) or quantum mechanically assessed electrophilic potencies) which implied that the reductive activation of the compounds may be one of the ascendant mechanisms of their action ( [11][12][13], and refs. therein).…”

“…therein). Many quantitative structure activity relationship (QSAR) studies emphasized the importance of lipophilic properties of NACs which correlated with toxic effects of the compounds as an additional descriptor on their electrophilic potency ( [13], and refs. therein).…”

“…Many efforts have been made to model accute toxicity of NACs applying a set of molecular descriptors, such as the energies of the highest occupied (E HO-MO ) and the lowest unoccupied (E LUMO ) molecular orbitals, the LUMO-HOMO energy gap (∆E H-L ) (or chemical hardness, η = E LUMO -E HOMO , or softness, S = 1/η), vertical and/or adiabatic ionization potentials (IPs) and electron affinities (EAs), electro-static densities, charges and potentials, molecular area and/or volume, (topological) polar surface area ((T)PSA), the numbers of hydrogen-bond donor (HBD) or hydrogen-bond acceptor (HBA), lipophilicity (log P and/or log D), a set of topological indices, etc. [13][14][15][16][17]. In addition, the efforts have been made to explore the DFT-based reactivity indices of nitroaromatics for prediction of their toxicity, viz., the chemical hardness (η), the chemical potential (µ) (or electronegativity, χ = -µ) and the electrophilicity (ω) ( [18], and refs.…”

In vivo toxicity of nitroaromatics: A comprehensive quantitative structure–activity relationship study

“…Nitroaromatic compounds and their toxicity have been at the forefront of many scientific studies [11][12][13][14][15][16]. In addition to experimental studies, there has also been a fair amount of computational research on these compounds including the study of toxicity, particularly as it pertains to the influence of quantum chemical descriptors [17,18].…”