D. R. Roy

Analyzing toxicity through electrophilicity.

SummaryThe toxicological structure-activity relationships are investigated using conceptual DFT based descriptors like global and local electrophilicities. In the present work the usefulness of electrophilicity in predicting toxicity of several polyaromatic hydrocarbons (PAH) is assessed. The toxicity is expressed through biological activity data (pIC50) defined as molar concentration of those chemicals necessary to displace 50% of radiolabeled tetrachlorodibenzo-p-dioxin (TCDD) from the arylhydrocarbon (Ah) receptor. The experimental toxicity values (pIC50) for the electron acceptor toxin like polychlorinated dibenzofurans (PCDF) are taken as dependent variables and the DFT based global descriptor electrophilicity index (ω) is taken as independent variable in the training set. The same model is then tested on a test set of polychlorinated biphenyls (PCB). A good correlation is obtained which vindicates the importance of these descriptors in the QSAR studies on toxins. These toxins act as electron acceptors in the presence of biomolecules whereas aliphatic amines behave as electron donors some of which are also taken into account for the present work. The toxicity values of the aliphatic amines in terms of the 50% inhibitory growth concentration (IGC50) towards ciliate fresh-water protozoa Tetrahymena pyriformis are considered. Since there is no global nucleophilicity we apply local nucleophilicity (ωmax+) as the descriptor in this case of training set. The same regression model is then applied to a test set of amino alcohols. Although the correlation is very good the statistical analysis reflects some cross validation problem. As a further check the amines and amino alcohols are used together to form both the training and the test sets to provide good correlation. It is demonstrated that the toxicity of several toxins (both electron donors and acceptors) in the gas and solution phases can be adequately explained in terms of global and local electrophilicities. Amount of charge transfer between the toxin and the biosystem, simulated as nucleic acid bases and DNA base pairs, indicates the importance of charge transfer in the observed toxicity. The major strength of the present analysis vis-à-vis the existing ones rests on the fact that it requires only one descriptor having a direct relationship with toxicity to provide a better correlation. Importance of using the information from both the toxin and the biosystem is also analyzed.

Reactivity, Selectivity, and Aromaticity of Be32-and Its Complexes

The stability, reactivity, and aromaticity of the Be32- dianion and its bimetallic species are investigated. The aromaticity of these systems is analyzed in the light of the DFT-based reactivity descriptors, namely, hardness (eta) and polarizability (alpha), molecular orbital (MO) analysis, and the nucleus-independent chemical shift (NICS). The recently discovered direct Zn-Zn bond is stabilized through the complexation with Be32-, and a new compound [(Be3)2Zn2]2- is reported. The chemical nature and selectivity of the Be32- unit in its bimetallic form are analyzed using the atomic charge (Qk) and nucleophilicity excess (Deltaomega++g) descriptors to examine its applicability in the field of molecular electronics.

Magnetic moment and local moment alignment in anionic and/or oxidized Fen clusters

First principles studies on the ground state structure, binding energy, spin multiplicity, and the noncollinearity of local spin moments in Fe(n) and Fe(n) (-) clusters and their oxides, viz., Fe(n)O(2) and Fe(n)O(2) (-) have been carried out within a density functional formalism. The ground states of Fe(n) and Fe(n) (-) clusters have collinear spins with a magnetic moment of around 3.0 micro(B) per atom. The O(2) molecule is found to be dissociatively absorbed and its most significant effect on spin occurs in Fe(2), where Fe(2)O(2) and Fe(2)O(2) (-) show antiferromagnetic and noncollinear spin arrangements, respectively. The calculated adiabatic electron affinity and the vertical transitions from the anion to the neutral species are found to be in good agreement with the available negative ion photodetachment spectra, providing support to the calculated ground states including the noncollinear ones.

A conceptual DFT approach towards analysing toxicity

The applicability of DFT-based descriptors for the development of toxicological structure-activity 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 (pIC50). 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 (pIC50) for the family of PAH, namely polychlorinated dibenzofurans (PCDF), poly-halogenated 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.

Synthesis and structure of 1-D Na6 cluster chain with short Na-Na distance : Organic like aromaticity in inorganic metal cluster

A unique 1-D chain of sodium cluster containing (Na6) rings stabilized by a molybdenum containing metalloligand has been synthesized and characterized and the DFT calculations show striking resemblance in their aromatic behaviour with the corresponding hydrocarbon analogues.

Bonding, aromaticity, and structure of trigonal dianion metal clusters.

Various isomers of the trigonal dianion metal clusters, X  32− , X = Be, Mg, Ca, and their mono‐ and disodium complexes are optimized at the B3LYP/6‐311+G(d) level. Different conceptual density functional theory based reactivity descriptors as well as the induced magnetic field values are calculated to understand the stability and aromaticity of these systems. Possibility of bond stretch isomerism is explored. Genetic algorithm results lend additional insights into the structures of these isomers.

Aromaticity in cyclic alkali clusters

Density functional calculations on a hexagonal 1D sodium cluster and a 2D potassium cluster show that the M6 (M = Na, K) rings in the chain present in 3D [Na2MoO3L(H2O)2]n (1) and 2D [K2MoO3L(H2O)3]n (2) are aromatic in character according to the nucleus independent chemical shift (NICS) and multicenter bond indices (MCI) values. The NICS values at the center of the Na6 rings and at the cage center of the K6 rings are comparable to the corresponding values of their polyacene analogues in most cases. The stability and reactivity patterns of the M6 rings also follow a similar trend as their organic analogues.

Minimum magnetizability principle

A new electronic structure principle, viz., the minimum magnetizability principle, has been proposed and also has been verified through ab initio calculations, to extend the domain of applicability of the conceptual density functional theory in explaining the magnetic interactions and magnetochemistry. This principle may be stated as “a stable configuration/conformation of a molecule or a favorable chemical process is associated with a minimum value of the magnetizability.” The behavior of paramagnetic and diamagnetic components has been separately studied.

Highly Sensitive Bifunctional Probe for Colorimetric Cyanide and Fluorometric H2S Detection and Bioimaging: Spontaneous Resolution, Aggregation, and Multicolor Fluorescence of Bisulfide Adduct

A 4-methylbenzothiazole linked maleimide-based single molecular bifunctional probe 1 has been synthesized for the colorimetric and fluorometric detection of highly competitive H2S and cyanide ion in aqueous DMSO media. The probe 1 selectively detected CN- under the UV-vis spectroscopy through the rapid appearance of deep pink color. The bright pink color developed due to ICT in the moderately stable cyano substituted enolate intermediate. The absorbance titration of 1 with CN- revealed a new band at 540 nm and the nonlinear curve fitting analysis showed good fit with 1:1 model. In fluorescence channel, 1 was found to be highly selective to H2S in 50% aqueous buffer (pH 7). It exhibited ∼16-fold fluorescence intensity enhancement at 435 nm after reaction with 1 equiv of H2S due to the inhibition of PET. The 1-SH adduct showed TICT phenomenon and behaved like molecular rotor. It further displayed aggregation behavior at higher concentration and excitation wavelength dependent multicolor emission properties. Most interestingly, the spontaneous resolution of chiral S-isomer of the 1-SH adduct occurred during crystallization. The cell imaging study revealed the staining of the cell and multicolor emission in the presence of H2S.

Arsenic toxicity: an atom counting and electrophilicity-based protocol

The atomic number (Z) and electrophilicity index (ω) have been utilized to explain the toxicity of various alkali and transition-metal ions as well as to predict that of the arsenic ions. The toxicity of two different training sets of arsenic derivatives is described using the global electrophilicity (ω) and number of nonhydrogenic atoms (NNH) along with the local philicity