Bond stretch isomerism in Be32- driven by the Renner-Teller effect.

We investigate the underlying principle behind the occurrence of bond stretch isomerism in Be32-, which has not been revealed yet. Various computational studies of the different isomers are carried out at the complete active space self-consistent field (CASSCF) level of theory in addition to the B3LYP level in conjunction with the 6-311++G(d) basis set. The potential energy surfaces linking the different isomers through transition states and conical intersections are investigated at the CASSCF level, connecting various geometrical isomers of Be32-. The linear intermediate of the Be32- cluster is considered to be of profound importance since its excited state is found to be degenerate and undergoing the Renner-Teller effect, producing two triangular bond stretch isomers. Ab initio molecular dynamics simulations based on the Atom Centered Density Matrix Propagation (ADMP) method also further elucidate the phenomenon of isomerization via the linear intermediate. The variation of the global reactivity descriptors and free energy profile along the bond stretch isomerization path is also investigated. The estimated aromatic stabilization energy also corroborates the stability ordering of the bond stretch isomers.

A molecular dynamics study on sI hydrogen hydrate.

A molecular dynamics simulation is carried out to explore the possibility of using sI clathrate hydrate as hydrogen storage material. Metastable hydrogen hydrate structures are generated using the LAMMPS software. Different binding energies and radial distribution functions provide important insights into the behavior of the various types of hydrogen and oxygen atoms present in the system. Clathrate hydrate cages become more stable in the presence of guest molecules like hydrogen.

Pyrazine functionalized Ag(I) and Au(I)-NHC complexes are potential antibacterial agents.

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Bacteria can develop ways to render traditional antibiotics ineffective, raising a crucial need to find new antimicrobials with novel mode of action. We demonstrate here a novel class of pyrazine functionalized Ag(I) and Au(I)-NHC complexes as antibacterial agents against human pathogens that are resistant to several antibiotics. Complete synthetic and structural studies of Au(I) and Ag(I) complexes of 2-(1-methylimidazolium) pyrimidinechloride (L-1), 2,6-bis(1-methylimidazol)pyrazinechloride (L-2) and 2,6-bis(1-methyl imidazol) pyrazinehexa-fluorophosphate (L-3) are reported herein. Chloro[2,6-bis(1-methyl imidazol)pyrazine]gold(I), 2b and chloro [2,6-bis(1-methyl imidazol)pyrazine]silver(I), 2a complexes are found to have more potent antimicrobial activity than other synthesized compounds and several conventionally used antibiotics. Complexes 2b and 2a also inhibit the biofilm formation by Gram-positive bacteria, Streptococcus mutans and Gram-negative bacteria, Escherichia coli, causing drastic damage to the bacterial cell wall and increasing membrane permeability. Complexes 2b and 2a strongly binds to both Lys and Dap-Type peptidoglycan layers, which may be the reason for damage to the bacterial cell wall. Theoretical studies of all the complexes reveal that 2b and 2a are more reactive than other complexes, and this may be the cause of differences in antibacterial activity. These findings will pave the way towards developing a new class of antibiotics against different groups of conventional antibiotic-resistant bacteria.

Dirichlet boundary conditions and effect of confinement on chemical reactivity.

To understand the source of discrepancy in the qualitative trends in the reactivity of the spherically confined atoms/ions when the high pressure is generated through the use of a proper Dirichlet boundary condition [J. Chem. Sci. 2005, 117, 379; Phys. Chem. Chem. Phys. 2008, 10, 1406] and of a cutoff function [Chem. Phys. Lett. 2003, 372, 805; J. Phys. Chem. A 2003, 107, 4877], a modified Herman-Skilman program is run. Results obtained from different formulas of reactivity parameters are analyzed. Change in reactivity for different electronic configurations is also reported. It is observed that the use of different formulas is the major source of discrepancy and not the Dirichlet condition, although the latter is highly recommended. As the cutoff radius of the confining spherical box decreases, the energy of the atom/ion increases, the electronegativity decreases, and the hardness increases and ultimately slightly decreases in an ultraconfined situation. For small R(C) values, softness decreases and electrophilicity increases and attains relatively small values. The reactivity of confined atoms/ions is put in a proper perspective.

Comparison of Global Reactivity Descriptors Calculated Using Various Density Functionals: A QSAR Perspective.

Conceptual density functional theory (DFT) based global reactivity descriptors are used to understand the relationship between structure, stability, and global chemical reactivity. Furthermore, these descriptors are employed in the development of quantitative structure-activity (QSAR), structure-property (QSPR), and structure-toxicity (QSTR) relationships. However, the predictive power of various relationships depends on the reliable estimates of these descriptors. The basic working equations used to calculate these descriptors contain both the ionization potential and the electron affinity of chosen molecules. Therefore, efficiency of different density functionals (DFs) in predicting the ionization potential and the electron affinity has to be systematically evaluated. With a view to benchmark the method of calculation of global reactivity descriptors, comprehensive calculations have been carried out on a series of chlorinated benzenes using a variety of density functionals employing different basis sets. In addition, to assess the utility of global reactivity descriptors, the relationships between the reactivity-electrophilicity and the structure-toxicity have been developed. The ionization potential and the electron affinity values obtained from M05-2X method using the ΔSCF approach are closer to the corresponding experimental values. This method reliably predicts these electronic properties when compared to the other DFT methods. The analysis of a series of QSTR equations reveals that computationally economic DFT functionals can be effectively and routinely applied in the development of QSAR/QSPR/QSTR.

Initial Hardness Response and Hardness Profiles in the Study of Woodward-Hoffmann Rules for Electrocyclizations.

The fundamental principles of pericyclic reactions are governed by the Woodward-Hoffmann rules, which state that these reactions can only take place if the symmetries of the reactants' molecular orbitals and the products' molecular orbitals are the same. As such, these rules rely on the nodal structure of either the wave function or the frontier molecular orbitals, so it is unclear how these rules can be recovered in the density functional reactivity theory (or "conceptual DFT"), where the basic quantity is the strictly positive electron density. A third, nonsymmetry based approach to predict the outcome of pericyclic reactions is due to Zimmerman which uses the concept of the aromatic transition states: allowed reactions possess aromatic transition states, while forbidden reactions possess antiaromatic transition states. Based on our recent work on cycloadditions, we investigate the initial response of the chemical hardness, a central DFT based reactivity index, along the reaction profiles of a series of electrocyclizations. For a number of cases, we also compute complete initial reaction coordinate (IRC) paths and hardness profiles. We find that the hardness response is always higher for the allowed modes than for the forbidden modes. This suggests that the initial hardness response along the IRC is the key for casting the Woodward-Hoffmann rules into conceptual DFT.

Multiphilic descriptor for chemical reactivity and selectivity.

In line with the local philicity concept proposed by Chattaraj et al. (Chattaraj, P. K.; Maiti, B.; Sarkar, U. J. Phys. Chem. A. 2003, 107, 4973) and a dual descriptor derived by Morell, Grand and Toro-Labbé, (J. Phys. Chem. A 2005, 109, 205), we propose a multiphilic descriptor. It is defined as the difference between nucleophilic (omega(k)+) and electrophilic (omega(k)-) condensed philicity functions. This descriptor is capable of simultaneously explaining the nucleophilicity and electrophilicity of the given atomic sites in the molecule. Variation of these quantities along the path of a soft reaction is also analyzed. Predictive ability of this descriptor has been successfully tested on the selected systems and reactions. Corresponding force profiles are also analyzed in some representative cases. Also, to study the intra- and intermolecular reactivities another related descriptor, namely, the nucleophilicity excess (Deltaomega(g)-/+) for a nucleophile over the electrophilicity in it, has been defined and tested on all-metal aromatic compounds.

An atom counting strategy towards analyzing the biological activity of sex hormones.

A simple and effective molecular descriptor, viz., the number of atoms in a molecule (N(A)) is made use of in the development of the quantitative structure-activity relationship (QSAR). A series of testosterone derivatives with various biological activities and estrogen derivatives with the activities in terms of relative binding affinity (RBA) are considered to find out the potential of N(A) in predicting the activities of those molecules. It is heartening to note that N(A) along with the electrophilicity index (omega) is capable of explaining the biological activities of the male and female hormones.

Electrophilicity-based charge transfer descriptor.

In line with the charge transfer (DeltaNmax = -mu/eta) proposed by Parr et al. (Parr, R. G.; Szentpály, L. V.; Liu, S. J. Am. Chem. Soc. 1999, 121, 1922), we propose an electrophilicity-based charge transfer (ECT) descriptor in this paper and validate it through the interaction between a series of chlorophenols and DNA bases. Application of ECT can be extended to the interaction of any toxin with the biosystem.

Theoretical study on the complete series of chloroanilines.

The environmental effects of chloroanilines depend on their physical and chemical properties, and it is therefore important to know their structure-property relationships that allow a complete understanding of their environmental consequences. The chemical reactivity profiles of all 19 chloroanilines have been investigated using the density functional theory for the first time. Global reactivity descriptors, such as hardness, chemical potential, electrophilicity index, and polarizability, and local reactivity descriptors, namely, local philicities, have been calculated in order to gain insights into the reactive nature and the reactive sites of the selected systems. Using AIM theory, the presence of hydrogen bond critical points (HBCPs) and the values of electron density and Laplacian of electron density at the HBCPs have been analyzed to appreciate the presence of intramolecular hydrogen bonding in the selected systems. Structure-toxicity analysis of the selected set of chloroanilines demonstrates the importance of the electrophilicity index in the prediction of reactivity/toxicity.

Analyzing toxicity through electrophilicity.

The 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 (omega) 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 (omegamax+) 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.

pKa prediction using group philicity.

Acid-base dissociation constants (pK(a) values) are important in understanding the chemical, environmental and toxicological properties of molecules. Though various methods have been developed to predict pK(a) by experimental and theoretical models, prediction of pK(a) is still complicated. Hence, a new approach for predicting pK(a) using the group philicity concept has been attempted. Presence of known functional groups in a molecule is utilized as the most important indicator to predict pK(a). The power of this descriptor in describing pK(a) for the series of carboxylic acids, various substituted phenols, anilines, phosphoric acids, and alcohols is probed. Results reveal that the group electrophilicity is suitable for effectively predicting the pK(a) values.

Group philicity and electrophilicity as possible descriptors for modeling ecotoxicity applied to chlorophenols.

The search for the best quantitative structure-activity relationship (QSAR) models in ecotoxicology is an ever-topical research activity. Hence, the development of new descriptors and applying them successfully in QSAR studies seems demanding in ecotoxicology. In the present work, group philicities are utilized for the first time in QSAR analysis for ecotoxicological studies on chlorophenols (CPs). It is important to point out that group philicities are capable of providing the best QSAR model for the toxicity of CPs against Daphnia magna. Furthermore, global electrophilicity and group philicities together give the best QSAR models for Brachydanio rerio and Bacillus with the maximum value of coefficient of determination and high internal predictive ability. The developed QSAR models clearly show the importance of the selected density functional reactivity indices as descriptors in ecotoxicological studies.

Chemical reactivity indices for the complete series of chlorinated benzenes: solvent effect.

We present a comprehensive analysis to probe the effect of solvation on the reactivity of the complete series of chlorobenzenes through the conceptual density functional theory (DFT)-based global and local descriptors. We propose a multiphilic descriptor in this study to explore the nature of attack at a particular site in a molecule. It is defined as the difference between nucleophilic and electrophilic condensed philicity functions. This descriptor is capable of explaining both the nucleophilicity and electrophilicity of the given atomic sites in the molecule simultaneously. The predictive ability of this descriptor is tested on the complete series of chlorobenzenes in gas and solvent media. A structure-toxicity analysis of these entire sets of chlorobenzenes toward aquatic organisms demonstrates the importance of the electrophilicity index in the prediction of the reactivity/toxicity.

Careful scrutiny of the philicity concept.

The philicity concept [J. Phys. Chem. A 2003, 107, 4973] is put in proper perspective. In the present work we analyze different physicochemical problems using philicity. It provides satisfactory results in all such cases. We also compare the relative electro(nucleo)philicity with philicity to show that philicity is better than relative electro(nucleo)philicity when the intermolecular reactivity trends are considered and there is hardly any preference of one above the other as far as the intramolecular reactivities are concerned. On the contrary, the philicity concept has some advantages over the other concept.

QSPR models for polychlorinated biphenyls: n-Octanol/water partition coefficient.

The logarithmic n-octanol/water partition coefficient (logK(ow)) is an important property for pharmacology, toxicology and medicinal chemistry. Quantitative structure-property relationship (QSPR) model for the lipophilic behaviour (logK(ow)) of the data set containing 133 polychlorinated biphenyl (PCB) congeners is analyzed using the conceptual density functional theory based global reactivity parameter such as electrophilicity index (omega) along with energy of lowest unoccupied molecular orbital (E(LUMO)) and number of chlorine substituents (N(Cl)) as descriptors. A reasonably good coefficient of determination (r(2) = 0.914) and the internal predictive ability (r(cv)(2) = 0.909) values are obtained indicating the significance of the considered descriptors in the property analysis of PCBs. Further, the developed method has widespread applicability from chemical reactivity to toxicity analysis and in studies related to various physicochemical properties in the series of dioxins and other polyaromatic hydrocarbons.

Molecular structure, reactivity, and toxicity of the complete series of chlorinated benzenes.

The structure and chemical reactivity profiles of all 12 chlorobenzenes have been investigated using the density functional theory and ab initio molecular orbital calculations. Global and local reactivity descriptors such as electrophilicity index and local philicity, respectively, of the selected systems have been calculated in order to gain insights into the reactive nature and the reactive sites of these compounds. Also, the effects of chlorine substitution on the aromaticity of the compounds have been analyzed by calculating the nucleus-independent chemical shift. Interaction through charge transfer between chlorobenzenes and nucleic acid bases/selected base pairs are determined using Parr's formula. The results revealed that the chlorobenzenes act as electron acceptors in their interaction with biomolecules. Structure-toxicity analysis of this entire set of chlorobenzenes demonstrates the importance of the electrophilicity index in the prediction of reactivity/toxicity.

Electrophilicity as a possible descriptor for toxicity prediction.

Electrophilicity is one of the cardinal chemical reactivity descriptors successfully employed in various molecular reactivity studies within a structure-activity relationship parlance. The applications of this quantity in the modeling of toxicological properties have inspired us to perform a more exhaustive study in order to test and/or to validate the application of electrophilicity in assessing its chemical and toxicological potential. For this reason the toxicity of a large data set of molecules comprising 252 aliphatic compounds on the Tetrahymena pyriformis is studied. A quantitative structure-activity relationship analysis enabled us to model toxicity in terms of global and local electrophilicities, which provide a reasonably good prediction of aliphatic toxicity. It is heartening to note that the global and local electrophilicity values together can explain the toxicity of a large variety of aliphatic compounds nicely without resorting to any other descriptor or other microscopic/macroscopic physicochemical properties as is the situation in all other QSAR studies.

Stability and reactivity of all-metal aromatic and antiaromatic systems in light of the principles of maximum hardness and minimum polarizability.

It is demonstrated that among various possible isomers of all-metal aromatic compounds such as Al(4)(2-) and their complexes the most stable isomer with the minimum energy is the hardest and the least polarizable. A similar situation is observed for different isomers of all-metal antiaromatic compounds such as Al(4)(4-) and their complexes. It is shown that linear Al(4)(4-) is energetically more stable than its cyclic isomer. The reaction energies associated with the complexation processes highlight the stability of those complexes. The difference in energy, hardness, and polarizability between a cyclic molecule and its linear counterpart convincingly shows that an aromatic molecule exhibits negative changes in energy and polarizability but positive changes in hardness as expected from the principles of minimum energy, minimum polarizability, and maximum hardness. Although the aromaticity of Al(4)(2-) is unequivocally established through this study, the antiaromaticity picture in the case of Al(4)(4-) is shown to be poorly understood;however, the present analysis sheds light on this controversy.

Electrophilicity index as a possible descriptor of biological activity.

The purpose of this study is to probe the suitability of DFT based chemical reactivity parameter, electrophilicity index as a possible biological activity descriptor in the development of QSAR. Testosterone derivatives with activity described in terms of various biological activity parameters and the estrogen derivatives by relative binding affinity (RBA) values have been selected as model systems. The implications for the ability of electrophilicity to describe the biological activities are discussed. From the results it is possible to observe that electrophilicity index may be suitable to effectively describe the biological activity.