Molecular Electrostatic Properties Research Articles

DFT and MD simulation investigation of favipiravir as an emerging antiviral option against viral protease (3CLpro) of SARS-CoV-2

As per date, around 20 million COVID-19 cases reported from across the globe due to a tiny 125 nm sized virus: SARS-CoV-2 which has created a pandemic and left an unforgettable impact on our world. Besides vaccine, medical community is in a race to identify an effective drug, which can fight against this disease effectively. Favipiravir (F) has recently attracted too much attention as an effective repurposed drug against COVID-19. In the present study, the pertinency of F has been tested as an antiviral option against viral protease (3CLpro) of SARS-CoV-2 with the help of density functional theory (DFT) and MD Simulation. Different electronic properties of F such as atomic charges, molecular electrostatic properties (MEP), chemical reactivity and absorption analysis have been studied by DFT. In order to understand the interaction and stability of inhibitor F against viral protease, molecular docking and MD simulation have been performed. Various output like interaction energies, number of intermolecular hydrogen bonding, binding energy etc. have established the elucidate role of F for the management of CoV-2 virus for which there is no approved therapies till now. Our findings highlighted the need to further evaluate F as a potential antiviral against SARS-CoV-2.

Photophysics, photochemistry and bioimaging application of 8-azapurine derivatives.

New 2-aryl-1,2,3-triazolopyrimidines were designed, synthesized, and characterized. Their optical properties were thoroughly studied in the solid phase, in solution and in a biological environment. Density Functional Theory (DFT) based calculations were performed, including the molecular geometry optimization for both the ground state and the first singlet excited state, the prediction of the UV-Vis absorption and fluorescence spectra, the determination of the molecular electrostatic properties and the solvent effect on the optical properties. The emission intensity was revealed to increase in time upon irradiation. Mass spectrometric research, quantum mechanical calculations, and analysis of literature data suggested a possible photo-transformation pathway through the homolytic cleavage of one of the C-Cl bonds upon irradiation with UV light. The structure of the active intermediate was identified by the series of mass spectrometry experiments and via synthesis of putative transformation products. The kinetic parameters measured in different solvents allowed estimating the rate of these photo-transformations. Biological experiments demonstrated that 2-aryl-1,2,3-triazolopyrimidines penetrate cells and selectively accumulate in the cell membrane and the Golgi complex and endoplasmic reticulum. Their unique properties pave the way for new possible applications of fluorescent 8-azapurines in biology and medicine.

Charge Distributions of Nitro Groups Within Organic Explosive Crystals: Effects on Sensitivity and Modeling

The charge distribution of NO2 groups within the crystalline polymorphs of energetic materials strongly affects their explosive properties. We use the recently introduced basis-space iterated stockholder atom partitioning of high-quality charge distributions to examine the approximations that can be made in modeling polymorphs and their physical properties, using 1,3,5-trinitroperhydro-1,3,5-triazine, trinitrotoluene, 1-3-5-trinitrobenzene, and hexanitrobenzene as exemplars. The NO2 charge distribution is strongly affected by the neighboring atoms, the rest of the molecules, and also significantly by the NO2 torsion angle within the possible variations found in observed crystal structures. Thus, the proposed correlations between the molecular electrostatic properties, such as trigger-bond potential or maxima in the electrostatic potential, and impact sensitivity will be affected by the changes in conformation that occur on crystallization. We establish the relationship between the NO2 torsion angle and the likelihood of occurrence in observed crystal structures, the conformational energy, and the charge and dipole magnitude on each atom, and how this varies with the neighboring groups. We examine the effect of analytically rotating the atomic multipole moments to model changes in torsion angle and establish that this is a viable approach for crystal structures but is not accurate enough to model the relative lattice energies. This establishes the basis of transferability of the NO2 charge distribution for realistic nonempirical model intermolecular potentials for simulating energetic materials.

Understanding the Inhibition Mechanism of a Supramolecular Complex as the Corrosion Inhibitor for Mild Steel in the Condensate Water

This work attempted to elucidate the corrosion inhibition mechanism of a supramolecular complex formed between β-cyclodextrin (β-CD) and octadecylamine (ODA) for mild steel in the condensate water. Molecular mechanics simulation was applied to determine the energy favored configuration of the complex and the possible orientation of ODA inside the β-CD cavity. Based on the results of gravimetric measurements, thermodynamics parameters for the adsorption process were calculated through Arrhenius and transition state equations. Scanning electron microscopy and X-ray photo electron spectroscopy were used for surface characterization. Density functional theory calculations (Mulliken charges and molecular electrostatic potential plot) were performed to clarify the adsorption mechanism of β-CD/ODA complex on the steel surface. It was found that four possible configurations of β-CD/ODA complex might be concurrent in the supramolecular system with the stable state in the aqueous solution. ODA molecules could break away from the β-CD cavity and chemically adsorbed on the metal surface, which obeyed the Langmuir adsorption isotherm. The inherent molecular electrostatic properties resulted in the tilted adsorption of ODA.

Multiphoton spectroscopy: An optical window into molecular electrostatics

Quantitative knowledge about static molecular electric dipole moments is essential for understanding of intramolecular charge transfer as well as nanometer-scale static electric interactions. However, measuring or determining the molecular electrostatic properties with sufficient accuracy remains a challenging task. In our experiments, we measure the femtosecond two-photon absorption spectra- and cross sections of a range of organic- and organometallic chromophores in solution and use these data to determine the electric dipole moment change in corresponding lowest-energy dipole-allowed transition. Good correspondence of our experimental dipole moments with the quantum-chemical calculations as well as reports by other groups using conventional dipole moment measurement methods suggests that quantitative multiphoton spectroscopy may offer all-optical alternative to the traditional techniques such as Stark effect and electrochromism.

Revisiting a many-body model for water based on a single polarizable site: From gas phase clusters to liquid and air/liquid water systems

We present a revised version of the water many-body model TCPE [M. Masella and J.-P. Flament, J. Chem. Phys. 107, 9105 (1997)], which is based on a static three charge sites and a single polarizable site to model the molecular electrostatic properties of water, and on an anisotropic short range many-body energy term specially designed to accurately model hydrogen bonding in water. The parameters of the revised model, denoted TCPE/2013, are here developed to reproduce the ab initio energetic and geometrical properties of small water clusters (up to hexamers) and the repulsive water interactions occurring in cation first hydration shells. The model parameters have also been refined to reproduce two liquid water properties at ambient conditions, the density and the vaporization enthalpy. Thanks to its computational efficiency, the new model range of applicability was validated by performing simulations of liquid water over a wide range of temperatures and pressures, as well as by investigating water liquid/vapor interfaces over a large range of temperatures. It is shown to reproduce several important water properties at an accurate enough level of precision, such as the existence liquid water density maxima up to a pressure of 1000 atm, the water boiling temperature, the properties of the water critical point (temperature, pressure, and density), and the existence of a "singularity" temperature at about 225 K in the supercooled regime. This model appears thus to be particularly well-suited for characterizing ion hydration properties under different temperature and pressure conditions, as well as in different phases and interfaces.

N-o-Vanillylidene-l-histidine: Experimental Charge Density Analysis of a Double Zwitterionic Amino Acid Schiff-Base Compound

A double zwitterionic Schiff base was synthesized using the amino acid l-histidine and o-vanillin (2-hydroxy-3-methoxy benzaldehyde). Both the phenol and carboxyl groups are deprotonated, and the imine nitrogen atom and histidine-imidazole ring are protonated to give the double zwitterion with an intramolecular (imine)N−H+···−O(phenol) hydrogen bond (ketoamine form). Such a ketoamine form in a double zwitterion is assumed in the catalytic cycle of enzymatic transformations of amino acids with the cofactor (vitamin B6) pyridoxal-5′-phosphate (PLP). A high-resolution, low-temperature, single-crystal X-ray diffraction data set on N-o-vanillylidene-l-histidine (also named 3-methoxysalicylidene-l-histidine or N-(2-oxy-3-methoxy-benzylidene)-l-histidine, OVHIS) is used in the analysis of molecular electrostatic properties and intermolecular interactions. All oxygen atoms in the molecule (four in total) are mutually almost coplanar and located (externally) on the same side of molecule. These four O atoms carry s...

General Methodology to Optimize Damping Functions to Account for Charge Penetration Effects in Electrostatic Calculations Using Multicentered Multipolar Expansions

We developed a methodology to optimize exponential damping functions to account for charge penetration effects when computing molecular electrostatic properties using the multicentered multipolar expansion method (MME). This methodology is based in the optimization of a damping parameter set using a two-step fast local fitting procedure and the ab initio (Hartree-Fock/6-31G** and 6-31G**+) electrostatic potential calculated in a set of concentric grid of points as reference. The principal aspect of the methodology is a first local fitting step which generates a focused initial guess to improve the performance of a simplex method avoiding the use of multiple runs and the choice of initial guesses. Three different strategies for the determination of optimized damping parameters were tested in the following studies: (1) investigation of the error in the calculation of the electrostatic interaction energy for five hydrogen-bonded dimers at standard and nonstandard hydrogen-bonded geometries and at nonequilibrium geometries; (2) calculation of the electrostatic molecular properties (potential and electric field) for eight small molecular systems (methanol, ammonia, water, formamide, dichloromethane, acetone, dimethyl sulfoxide, and acetonitrile) and for the 20 amino acids. Our results show that the methodology performs well not only for small molecules but also for relatively larger molecular systems. The analysis of the distinct parameter sets associated with different optimization strategies show that (i) a specific parameter set is more suitable and more general for electrostatic interaction energy calculations, with an average absolute error of 0.46 kcal/mol at hydrogen-bond geometries; (ii) a second parameter set is more suitable for electrostatic potential and electric field calculations at and outside the van der Waals (vdW) envelope, with an average error decrease >72% at the vdW surface. A more general amino acid damping parameter set was constructed from the original damping parameters derived for the small fragments and for the amino acids. This damping set is more insensitive to protein backbone and residue side-chain conformational changes and can be very useful for future docking and molecular dynamics protein simulations using ab initio based polarizable classical methods.

Molecular electrostatic properties using point charges: ab initio hybridization displacement charges combined with bond-centered charges

A new approximate scheme to compute hybridization displacement charges (HDC) in molecules at the ab initio level using bond-centered charges arising due to overlapping atomic orbitals has been developed. It has been applied at the SCF/6-31G** and SCF-CIS/6-31G** levels to the ground and excited states, respectively, of several polar and non-polar molecules. It is found that, statistically speaking, HDC computed using the present approach reproduce SCF dipole moments and surface molecular electrostatic potential (MEP) patterns quite satisfactorily. In some cases, HDC reproduce MEP features even somewhat better than the MEP-fitted CHelpG charges, particularly in molecules where MEP values around atoms vary rapidly, e.g. around the boron atom in certain molecules containing it, and homonuclear diatomic molecules. Some interesting information about molecular bonding, not available from other charge distributions, is revealed by the present approach, e.g. in lithium containing molecules. The present approach also appears to describe molecular electrostatic properties and molecular bonding better than that where the Löwdin's symmetry orthogonalized atomic orbitals are used.

Distribution of electrostatic potential around amphotericin B and its membrane targets

Amphotericin B is a well-known anti-fungal polyene macrolide antibiotic used widely in the treatment of systemic fungal infections. The molecular mechanism of the anti-fungal action of amphotericin B is still not elucidated and is under study. In the present article molecular electrostatic properties of amphotericin B and its membrane targets (cholesterol and ergosterol) were studied. The electrostatic potential around all three molecules was calculated using Poisson-Boltzmann methods. The physiological environment (water and membrane) was taken into account in these calculations. The distribution of electrostatic potential was presented on molecular surfaces. It was found that both targets have quite different electrostatic patterns that may be important for interaction with the antibiotic. The calculations of electrostatic potential for Amphotericin B also revealed some new features about the hydrophobic/hydrophilic pattern of this drug. The knowledge of how the electrostatic potential distributes around the studied molecules will be useful to build a model of amphotericin B-sterol channel.

Quantum pharmacologic studies applicable to the design of anticonvulsants: theoretical conformational analysis and structure-activity studies of barbiturates.

We report the first large-scale systematic quantitative structure-activity relationship (QSAR) study of barbiturates, correlating molecular structures with anticonvulsant activity. To achieve this QSAR study, we devised a four-step strategy. In step 1, an optimal quantum mechanical technique for determining the geometry and shape (conformation) of barbiturates was ascertained; this is the AM1 semiempirical molecular orbital method. In step 2, the AM1 method was used to optimize the structures and molecular properties of 48 barbiturates with varying anticonvulsant activity. In step 3, discriminant analysis and regression analysis statistical calculations were used to correlate the molecular properties of the 48 analogues against maximal electroshock (MES) and subcutaneous metrazol (s.c.Met)-induced seizures. In step 4, the contribution of molecular electrostatic properties to barbiturate anticonvulsant activity was further refined by quantum mechanical derived molecular electrostatic potential (MEP) maps. Using this four-step strategy, we defined the pharmacophore, the portion of a molecule responsible for bioactivity, for anti-MES and anti-s.c.Met activity. For anti-s.c.Met activity, barbiturate lipophilicity and geometry are important considerations; for anti-MES activity, barbiturate topologic and electronic properties have increased relevance.

Prediction of hydrogen bond basicity from computed molecular electrostatic properties: implications for comparative molecular field analysis

Computed molecular electrostatic properties have been evaluated as predictors of hydrogen bond basicity for a set of heterocycles with nitrogen as the hydrogen bond acceptor. The properties were (a) the electrostatic potential local minimum, Vmin, in the region of the nitrogen lone pair, (b) the electrostatic potential, Vβ(r), and (c) the magnitude of the electric field strength, |Fβ(r)|, at points along the lone pair axis, defined by the distance r from nitrogen. Vmin was found to be an excellent predictor of hydrogen bond basicity. The ability of the other parameters to fit the data was maximised at r= 1.4 Å for Vβ(r) and at r= 2.5 Å for |Fβ(r)| which has implications for Comparative Molecular Field Analysis.

Pseudoatoms in diatomic molecules: restricted radial functions

Molecular charge-density functions for several diatomic molecules of first-row atoms have been analyzed by the least-squares method with pseudoatoms that have restricted radial functions. Multipole expansions up to quadrupoles on the two centers with single exponential radial functions provide qualitative descriptions of the molecular charge densities. They do not provide accurate values of molecular electrostatic properties, however. Extension to octupoles and hexadecapoles does not improve the representation of physical properties. Variations of the valence exponents proved to be the most critical parameters for goodness of fit as well as for retrieval of physical properties. For the selected examples in this work it appears that the valence exponent is more sensitive to the atom type than to the bonding environment; the exception is the hydrogen pseudoatom.