Molecular Electrostatic Potential Surface Research Articles

Exploring the effect of substituents on the supramolecular assemblies built by non-covalent interactions in three closely related 1,3,4-oxadiazole-2(3H)-thione derivatives: An evaluation of antimicrobial and anti-proliferative activities

Three closely related 1,3,4-oxadiazole-2(3H)-thione N-Mannich bases were synthesized and characterized by spectroscopic and single crystal X-ray diffraction methods. X-ray analysis reveals that the title molecules adopt l-shaped conformation, and a slight structural deviation around substituent groups is noted. The Hirshfeld surface and 2D fingerprint plots demonstrate the effect of substituents (piperidine, morpholine, and thiomorpholine) on the intermolecular interactions. The CLP-PIXEL energy analysis identified the most significant interactions in the molecular dimers (that characterize the crystal packing) with respect to the total intermolecular interaction energies. These dimers are held together by various non-covalent interactions including C–H⋅⋅⋅S/N/O/Cl/π interactions in addition to unconventional lone pair⋅⋅⋅π interactions. A molecule with thiomorpholine substituent is favoured by two σ-hole interactions (Cl⋅⋅⋅Cl halogen bond and S⋅⋅⋅N chalcogen bond) in the solid state. Furthermore, the molecular electrostatic potential (MEP) surfaces and deformation electron density help to describe the existence of σ-hole on the Cl and thione S atoms. Noncovalent interaction index (NCI) and quantum theory of atoms in molecules (QTAIM) methods are used to delineate the nature of observed noncovalent interactions in the molecular dimers. In vitro data of antibacterial and anti-proliferative activities indicate that compound with morpholine substituent showed a moderate antibacterial activity against all tested Gram-positive bacterial strains. However, molecules with piperidine and thiomorpholine showed notable effectiveness against the HepG-2 cell line. Molecular docking analysis was performed with two liver cancer targets, VEGFR2 and RET, in order to understand the interactions between the ligand and the active site residues of these targets.

An atomic surface site interaction point description of non-covalent interactions.

Molecular electrostatic potential surfaces (MEPS) calculated using density functional theory have been used to develop a simplified description of the non-covalent interaction properties of organic molecules. The Atomic Interaction Point (AIP) model introduced here represents an evolution of the Surface Site Interaction Point (SSIP) model described previously, in which a molecule is represented by a discrete set of interaction points that define sites of interaction with other molecules. The interaction sites are described by interaction parameters that are equivalent to the experimentally determined H-bond donor and acceptor parameters α and β. By using high electron density MEPS that lie inside the van der Waals surface, it is possible to obtain accurate interaction parameters and locations for polar sites (s-holes, H-bond donors and acceptors), which are identified as local maxima and minima on the MEPS. For non-polar sites that represent π-systems and halogens, an approach based on molecular orbitals was used to assign the locations of the AIPs, and the interaction parameters were obtained using a lower electron density MEPS that lies close to the van der Waals surface. The AIP descriptions can be implemented directly in the Surface Site Interaction Point Model for Liquids at Equilibrium (SSIMPLE) to calculate solvation free energies, and the free energy of transfer of 1504 compounds from n-hexadecane to water was predicted with a root mean square error of 5 kJ mol-1. AIPs also provide a useful tool for mapping non-covalent interactions in intermolecular complexes, and examples are provided showing how X-ray crystal structures can be converted into AIP interaction maps that allow quantification of the free energy contributions of both polar and non-polar interactions to the stabilities of complexes in solution.

Zinc acetate-catalyzed, green and efficient synthesis of xanthene derivatives under ultrasound irradiation: X-ray crystallographic analysis and in silico study.

A simple, one-pot method using zinc acetate and ultrasound irradiation has been developed to synthesize xanthene derivatives from cyclic diketones and aromatic aldehydes, yielding good to excellent results. This method offers advantages like mild conditions, high atom economy, easy isolation, and a recyclable catalyst. All xanthene derivatives, including two new molecules, were confirmed using standard spectroscopic methods, with X-ray crystallographic data provided for compound 3r. The synthesized molecules were shown to inhibit the VEGFR-2 enzyme, confirmed by molecular docking studies. A 200 ns molecular dynamics simulation validated these findings, showing significant stability for the 3e-VEGFR-2 complex after 1 ns and the 3p-VEGFR-2 complex for 8 ns. DFT calculations were used to analyze electronic and geometric properties, including HOMO and LUMO bandgap energies and molecular electrostatic potential surfaces. Additionally, the absorption, distribution, metabolism, and excretion (ADME) properties of the synthesis compounds were assessed.

Improving the sublimation stability of ligustrazine with gallic acid by forming pharmaceutical cocrystal based on the Etter's rules

To improve the high sublimation characteristics of ligustrazine (TMP), an unreported ligustrazine-gallic acid pharmaceutical cocrystal (C7H6O5·2(C8H12N2)·H2O, TMP-GA) was synthesized by using a virtual cocrystal screening method based on the rules of hydrogen bonding formation (Etter's rules). The results of the molecular surface electrostatic potential (MEPS) of TMP-GA showed that the actual hydrogen bonding sites of TMP-GA were the same as the predicted ones, and the calculated ΔE was not much different from the predicted ones. The results of physicochemical properties showed that TMP-GA had better physical stability against TMP sublimation without reducing the solubility and permeability of TMP. Combined with the interaction force analysis of the crystals, the reason may be that compared with the TMP monomer pharmaceutical structure, the intermolecular hydrogen bonding of the TMP-GA pharmaceutical cocrystal is increased, the structure is more stable, and the increase in the energy required for TMP sublimation makes the tendency to sublimate of the TMP-GA significantly lower. This suggests that we can utilize the virtual cocrystal screening method based on Etter's rules to introduce suitable cocrystal formers to reduce the sublimation tendency of active pharmaceutical ingredients.

Negative cooperativity in the formation of H-bond networks involving primary anilines.

Networks of H-bonds can show non-additive behaviour, where the strength of one interaction perturbs another. The magnitude of such cooperative effects can be quantified by measuring the effect of the presence of an intramolecular H-bond at one site on a molecule on the association constant for formation of an intermolecular H-bond at another site. This approach has been used to quantify the cooperativity associated with the interaction of a primary amine with two H-bond acceptors. A series of compounds that have an intramolecular H-bond between an aniline NH2 group and a pyridine nitrogen were prepared, using polarising substituents on the pyridine ring to vary the strength of the intramolecular H-bond. The presence of the intramolecular interaction was confirmed by X-ray crystallography in the solid state and NMR spectroscopy in n-octane solution. UV-vis absorption titrations were used to measure the association constants for formation of an intermolecular H-bond with tri-n-butyl phosphine oxide in n-octane. Electron-donating substituents on the pyridine ring, which increase the strength of the intramolecular H-bond, were found to decrease the strength of the intermolecular H-bond between the aniline and the phosphine oxide. The results were used to determine the H-bond donor parameters for the anilines, α, and there is a linear relationship between the values of α and the H-bond acceptor parameter of the pyridine group involved in the intramolecular H-bond, β. The slope of this relationship was used to determine the cooperativity parameter (κ = -0.10), which quantifies the negative allosteric cooperativity between the two H-bonding interactions. Calculated molecular electrostatic potential surfaces of the anilines quantitatively reproduce the experimental result, which suggests that effects are electrostatic in origin, either due to polarisation of the NH bonds or due to secondary electrostatic interactions between the two H-bond acceptors.

Structural parameters of amphetamine: A DFT approach

The structural parameters of Amphetamine, a significant psychoactive drug, are investigated experimentally and computationally using spectroscopic and DFT methods. The molecule is subjected to optimization using the B3LYP functional with both 6-311+G (2d,p) and augmented cc-pVTZ basis sets. Resulting values are then compared against published crystal data for validation. Analysis of the Fourier Transform Infrared and Raman spectra is carried out with PED assignments and after scaling, the calculated spectral frequency values are verified with experimental spectra, revealing a favorable match between them. The NMR spectrum of the molecule is obtained using TD-DFT techniques. The quantum theory of atoms in molecules is employed to analyze the electron density distributions. The reactivity of the molecule is predicted using various tools including analysis of the molecular electrostatic potential surface, electron localized function, molecular graph, non-covalent interaction (NCI), Hirshfeld charge, frontier orbital as well as local and global reactivity descriptors. Natural bonding orbital analysis identifies the hybridization, charge transfer and correlation effects. The results of this study could be utilized for the development of novel chemical sensors for drug detection and to predict the correlation between the structure and pharmacological activity of various amphetamine derivatives.

Effects of solvents on structure and energy of 6-amino-2-mercapto-3H-pyrimidin-4-one: A computational study

6-amino-2-mercapto-3H-pyrimidin-4-one (AMP) is a π-conjugated organic molecule extensively used as a semiconductor in many optoelectronic devices. The computational hybrid meta-generalized gradient Minnesota M06-2x, ωB97XD, and B3LYP functionals in conjunction with the correlation consistent polarized valence triplet zeta (cc-pVTZ) basis set and the moderate composite CBS-QB3 procedure were used with the aid of the Gaussian 09 program and the kinetic and statistical thermodynamical package (KiSThelP) in the temperature range 250–400 K to investigate the behavior of AMP in the gas phase, and in different polar (water, ethanol), and non-polar (dimethyl sulfoxide (DMSO), acetone)) solvents. Non-linear optical (NLO) characteristics and quantum chemical parameters were examined. Natural bond orbital analysis (NBO) was used to characterize the charge transfer of the electron density in the investigated compounds. The quality of the methods used was inspected and compared to give accurate results. The stability of AMP can be returned to the hyper conjugative interactions that leading to its nonlinear optical activity. Also, the charge delocalization was analyzed using natural bond orbital technique. The molecular electrostatic potential surfaces (MEPS) plots have been generated. The rate coefficients of tautomerization processes (kuni, in s−1) were calculated from the transition state theory (TST) and unimolecular Rice-Ramsperger-Kassel-Marcus (RRKM) methods. The results indicate comparable chemical rates obtained from TST and RRKM. In addition, positive temperature dependencies were located for all channels and a high dominance of transferring H-atom from the external N-atom to the S-atom (R3 reaction) during the applied temperature range which can return to its lower activation energy. This study is the first stone in studying AMP under different conditions such as the atmosphere, combustion conditions and as a nano catalyst.

Insights into structural, vibrational, and chemical shift characteristics, solvents impact (polar and nonpolar) on electronic properties and reactive sites, ADMET predictions, and ligand-protein interactions for antiviral drugs safrole and isosafrole: An in-silico approach

The safrole and isosafrole are constitutional isomers that have been theoretically characterized utilizing Density Functional Theory (DFT) employed with the B3LYP/6-311++G(d,p) basis set to simulate geometrical parameters, vibrational aspects, electronic properties, and chemical shifts and explored the solvent effect on electronic spectra of safrole and isosafrole in different solvents, including polar solvents such as acetone, Dimethyl sulfoxide (DMSO), and methanol, nonpolar solvents such as chloroform, cyclohexane, and toluene, and the gas phase using Time Dependent-Density Functional Theory (TD-DFT) methods. In addition, Natural Orbital (NBO), Mulliken population analysis, and Molecular Electrostatic Potential (MEP) surface have been simulated to understand better the reactive sites in the molecular structures of safrole and isosafrole. The frontier molecular orbitals (FMO) energy gaps of safrole and isosafrole were simulated in polar and nonpolar solvents, confirming the safrole and isosafrole kinetic stability and chemical reactivity. The in-silico ADMET indices were utilized to ascertain the probable pharmacokinetic and biological features of safrole and isosafrole. A molecular docking investigation was also conducted to investigate the potential biological activity of safrole and isosafrole against the SARS-CoV-2 spike protein, providing more support for its antiviral efficacy.

Experimental and Theoretical Survey of Intramolecular Spodium Bonds/σ/π-Holes and Noncovalent Interactions in Trinuclear Zn(II)-Salen Type Complex with OCN- Ions: A Holistic View in Crystal Engineering.

In this work, one new centrosymmetric trinuclear Zn(II) complex 1, [{(OCN)Zn(L)}2Zn], using a salen-type ligand (H2L) in the presence of OCN- was synthesized and characterized via elemental, spectral, SEM-EDX, and single-crystal X-ray diffraction (SCXRD) study. In 1, SCXRD reveals two different stereochemical environments of zinc metal ions; one terminal Zn(II) center adopts square pyramidal geometries with the Addison parameter (τ) 0.095, and the central Zn(II) is tetracoordinated tetrahedral geometry. This article provides evidence of the significance and presence of spodium bonds (SpBs) in solid-state crystal structures involving a pseudotetrahedral environment of the central Zn-atom. X-ray structures reveal intramolecular Zn···O SpBs caused by the methoxy (-OCH3) substituent O-atom adjacent to the coordinated phenoxy O-atom. These noncovalent interactions have been thoroughly studied using density functional theory calculations at the RI-BP86[2]-D3[3]/def2-TZVP level of theory that characterizes the nature of SpBs, including the Baders quantum theory of atoms-in-molecules "QTAIM", molecular electrostatic potential (MEP) surface, and noncovalent index plot (NCI). In addition, a unique complex-isomer-based theoretical model has been vividly employed to estimate the SpBs energy in the complex. Natural bond orbital (NBO) analysis also tries to establish the differentiation between σ-hole and π-hole SpBs' natures more authentically. The complex energy frameworks were used to investigate noncovalent interactions. To better understand the different intermolecular interactions, we conducted a Hirshfeld surface, which revealed N···H (15.4%) and O···H (9.1%) contacts and Zn···O (5.1%) (SpBs).

Molecular Structure, Geometry Properties, HOMO-LUMO, and MEP Analysis of Acrylic Acid Based on DFT Calculations

In this paper, quantum computational chemistry methods were employed to calculate the molecular properties of acyrilic acid. The molecule was optimized at STO-3G basis set using Density Functional Theory (DFT/B3LYP). The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of the frontier orbitals were obtained using DFT. The energy gap of HOMO–LUMO orbitals has been found to be 5.545 eV. Molecular Electrostatic Potential (MEP) surface analyses were also investigated. In addition, the basic crystal structure properties of acrylic acid were shown via the Crystallographic Information File (CIF). A discussion of the fundamental theory was reported behind the characterization methods.

2,3-Dichloropyridine solubility in 14 pure solvents: Determination, correlation, Hansen solubility parameter, solvent effect and thermodynamic analysis

The solid–liquid equilibrium data of 2,3-dichloropyridine(23DCP) in 14 pure solvents were measured making use of the laser dynamic monitoring at 278.15/283.15/288.15 K − 313.15 K with 0.1 MPa. The findings of this study showed that the solubility increase of 23DCP in 14 pure solvents had a positive relation with temperature, and the solubility order was 1,4-dioxane > dichloromethane > n-butyl acetate > ethyl acetate > methyl acetate > acetonitrile > n-butanol > isobutyl alcohol > n-propanol > isopropanol > ethanol > cyclohexane > methanol > n-hexane. The solubility data of 23DCP was operated by seven models (Van't Hoff, modified Apelblat, λh, Yaws, NRTL, NRTL-SAC, Wilson) to correlate. And the average ARD values were 1.684 %,1.058 %, 1.031 %, 0.905 %, 0.937 %, 1.012 %, 2.062 % and the average 103RMSD values were 1.978, 1.396, 1.542, 1.221, 1.758, 1.658 and 1.883, respectively. In addition, Hansen solubility parameters were well evaluated to appraise the miscibility of 23DCP in 14 pure solvents. And the interactions between molecules were studied by means of molecular electrostatic potential surface, Hirshfeld surface analysis and density functional theory calculation. Finally, according to Van't Hoff equation, ΔsolG°, ΔsolH° and ΔsolS° of 23DCP in 14 pure solvents were got. ΔsolH° and ΔsolS° were bigger than zero, representing that this was a dissolution process of endothermic and entropy increase.

Computational study on the structural features, vibrational aspects, chemical shifts, and electronic properties of 1,4-Dinitrosopiperazine-2-carboxylic acid: Insights into donor-acceptor interactions and thermodynamic properties

This study employs computational simulations to comprehensively investigate the molecular properties of 1,4-Dinitrosopiperazine-2-carboxylic acid. Through rigorous analysis, the research explores the compound's structural characteristics, vibrational assignments, chemical shifts, electronic properties, donor-acceptor interactions, Mulliken atomic charges, molecular electrostatic potential surface (MESP), and thermodynamic parameters. The findings provide intricate insights into the behavior of the compound, unveiling potential applications in diverse chemical contexts. This thorough examination contributes significantly to our understanding of the fundamental properties of 1,4-Dinitrosopiperazine-2-carboxylic acid, offering invaluable knowledge for both further research endeavors and practical applications. The detailed elucidation of these properties holds promise for advancements in various fields, from pharmaceuticals to materials science, marking a significant stride towards harnessing the full potential of this compound in contemporary chemistry.

Quantum chemical calculation, topological analysis, biological evaluation and molecular docking of allo‐ocimenol against breast cancer

AbstractThe main aim of this study is to identify the structural stability of allo‐ocimenol and its molecular reactivity against breast cancer‐associated proteins to confirm its anti‐cancer capability using density function theory and molecular docking analysis. The structural optimization was carried out via the DFT/B3LYP technique with a 6‐311++G (d,p) basis set. The molecular geometry and vibrational assignments of the Allo‐Ocimenol molecule were analyzed through density functional theory (DFT). Through optimized molecular structure, the vibrational frequencies (FT‐IR and FT‐Raman) were assigned and related with experimentally observed vibrational frequencies and the UV spectrum was computed and experimentally confirmed. The allo‐ocimenol's reactive activity was further analyzed through a computed molecular electrostatic potential surface. Utilizing the HOMO‐LUMO energies and molecular electrostatic potential energy gap, the reactivity and molecular stability of the allo‐ocimenol molecule was calculated. Mulliken and natural population analyses were used to determine the charge distribution across the allo‐ocimenol atoms. The natural bond orbitals were used to demonstrate the bioactivity of the titled molecule. RDG evaluation was used to examine the weak interactions of the allo‐ocimenol molecule. ELF and LOL analyses were utilized to investigate the topology of the allo‐ocimenol molecule. Thermodynamic evaluation has been utilized to acquire values and asses the thermodynamic parameters that reveal the thermal stability of the title molecule. Allo‐Ocimenol's anti‐microbial activity was assessed through an in‐vitro disc diffusion method, and its tumor inhibitory and pharmacokinetic properties were evaluated through an in‐silico approach using molecular docking and ADMET investigation. Zones of clearance were seen in anti‐microbial analyses at various concentrations, and the breast cancer target protein NAMPT established the greatest binding potential, with a docking value of −7.4 Kcal mol−1.

Investigation of structure-property relationships for triazine-based star-shaped monomers consisting of different carbazole units: A theoretical and experimental study

Combined experimental and theoretical studies in the elucidation of the structure-property relationships of molecules are very guiding for advanced material designs. In this work, a comprehensive investigation of the structural, spectroscopic, and electronic properties of triazine-based star-shaped monomers composed of different carbazole constituents by theoretical and experimental methods has been presented. For this purpose, firstly, triazine-based star-shaped monomers consisting of different carbazole constituents in donor-acceptor configurations have been synthesized. The structural and spectroscopic characterizations of monomers obtained have been elucidated by means of 1H NMR, 13C NMR, FT-IR, FT-Raman, and UV–vis analysis. Theoretical calculations have been carried out by ab-initio methods based on Density Functional Theory (DFT) with the basis set of 6-31G(d,p). Additionally, electronic properties, molecular electrostatic potential (MEP) surface and vibrational modes have been calculated for the star-shaped monomers. It is seen that all the data obtained theoretically and experimentally are consistent with each other.

Synthesis, solvent-solute interactions (polar and non-polar), spectroscopic insights, topological aspects, Fukui functions, molecular docking, ADME, and donor-acceptor investigations of 2-(trifluoromethyl)benzimidazole: A promising candidate for antitumor pharmacotherapy

The favorite heteroatom-containing compound, 2-(trifluoromethyl) benzimidazole (2TFMBI), was synthesized and experimentally characterized using spectroscopic techniques. Density Functional Theory (DFT) with B3LYP/6–311++G(d,p) basis set was employed to simulate geometrical parameters, vibrational spectra, electronic spectra, chemical shifts, and other properties of 2TFMBI. Solvent effects, including aprotic polar (aniline and DMSO), protic polar (methanol and water), and non-polar (carbon tetrachloride, chloroform, cyclohexane, and toluene), on electronic properties, frontier molecular orbitals (FMO), and Molecular Electrostatic Potential Surface (MESP) were analyzed. Additionally, Natural Bond Orbital (NBO) and Mulliken population analysis were simulated to better understand the structural aspects of 2TFMBI. The energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) confirms the compound's high reactivity and charge transfer. In-silico Absorption, Distribution, Metabolism, and Excretion (ADME) indices were determined to have potential pharmacokinetic attributes and biological properties. A set of topological analyses, including Electron Localization Function (ELF), Local Orbital Locator (LOL), Non-Covalent Interaction (NCI), Reduced Density Gradient (RDG), and Quantum Theory of Atoms in Molecules (QTAIM) was performed to reveal weak interactions within the compound, spanning both chemical functionalities and delocalized zones. Furthermore, molecular docking analysis was performed to examine the potential biological activity against tumor-inducing proteins H-RASGTP and H-RASGDP, endorsing the antitumor efficacy of 2TFMBI.

Synthesis, structure–activity relationship studies using density functional theory and in silico molecular docking on substituted benzohydrazide derivatives

The present study demonstrates the utility of benzohydrazide derivatives based on an approach to identify potential targets for a series of synthesized compounds that show potent anticancer activities against four cancer cell lines compared to other structurally related molecules. Benzohydrazide compounds have been synthesized effectively by the condensation of aldehyde and hydrazide at a 1:1 molar ratio. The complete series of compounds 1a-j were characterized by FT-IR, NMR, and one of them by single-crystal X-ray diffraction. The crystal structure of compound 1a shows a trans configuration around the CN bond and crystallized in a monoclinic system with C 2/c space group. All compounds exhibited good anticancer activity against four cancer cell lines such as A375 (human malignant melanoma), A549 (human lung adenocarcinoma), HT-29 (human epithelial intestinal) and MDA-MB-232(human metastatic breast). Among them, compound 1e shows the highest cytotoxic effect against the HT29 (IC50 = 0.47 µM) and A375 (IC50 = 0.80 µM) cell lines. Other compounds also exhibited promising anticancer activity. In addition, the nontoxic action was verified using the cytocompatibility assay on the L929 normal cell line and the hemolysis assay on human red blood cells. Parameters such as HOMO-LUMO energies, Hirshfeld surface analysis, and Molecular Electrostatic Potential (MEP) surface have been calculated using DFT and compared to experimental values of compounds 1a-c. In silico molecular docking studies revealed that the compound 1 h interacted very strongly with the 1T46 protein, with a docking score of −9.7 kcal/mol and very good binding via π–π, π-alkyl and π–σ interactions as compared to the standard drug. As a result of their potent cytotoxicity activities and computational analysis, these can be considered promising anticancer agents.

Uncovering dissolution behavior and thermodynamic properties of metronidazole benzoate in twelve mono-solvents by experiments and molecular simulation

In this study, metronidazole benzoate (MBZ), a nitroimidazole antibiotic, was selected to measure the solubility in 12 solvents by the gravimetric method in the temperature range of 278.15 K to 323.15 K. The intermolecular interactions dominated by H···H and O···H contacts in the solid phase were determined using Hirshfeld surface analysis (HS). Subsequently, molecular simulations involving molecular electrostatic potential surface (MEPs), hydrogen binding energy (EHB) and mean square displacement (MSD) revealed the effect of the solvent polarity, hydrogen bonding and diffusion process on the dissolution behavior of MBZ. Furthermore, six thermodynamic models, all with values of ARDs less than 5 %, were successfully correlated with the experimental solubility results. The Apelblat model achieved the best fitting. Based on the NRTL models, relevant thermodynamic parameters were obtained, indicating that the dissolution process of MBZ in various solvents is spontaneous and entropy-driven. In the measured temperature range, the solubility of MBZ in different solvents increased from 4-times to 25-times as the temperature changed, which provided an important theoretical basis for the industrial production of MBZ.

Spectroscopic (FTIR, FT-Raman, UV–Vis) studies, NMR, NBO analysis, molecular docking studies on 2-cyano-5-fluoropyridine and 3-cyano-2-fluoropyridine

In this present work, to investigate the physicochemical properties of the molecules, extensive quantum chemical calculations have been performed on 2-cyano-5-fluoropyridine (2C5FP) and 3-cyano-2-fluoropyridine (3C2FP). Infrared and Raman spectra analysis have been carried out to study the vibrational modes of the molecule. Based on density function theory (DFT) with 6–311 ++ G (d, p) basis set, was also used to compute the same modes. As a result of intramolecular interactions, charge transfer or delocalization of charge has been explained by natural bond orbital analysis. The NMR study was also carried out experimentally and theoretically. The nucleophilic and electrophilic sites were predicted by Molecular Electrostatic Potential surface (MEP). By using the same functional and basis set and GIAO method, theoretical predictions were made. The absorption wavelengths of title molecules have been studied both theoretically and experimentally using UV–visible analysis. The Mullikan population analysis and Natural atomic charges are used to calculate the net charges of the atoms in the molecules, and the calculated net charges are compared to the experimental chemical shift values. A molecular docking study revealed that the title molecules may have antidiabetic properties when bound to protein Glycogen Phosphorylase B Complexed Glucose.

Monohalogenated methyl- and methoxy-benzoic acids: A combined experimental and quantum chemical theoretical study on their structure, vibrational analysis and molecular parameters

In this paper, the molecules 3-fluoro-2-methylbenzoic acid; 3-chloro-2-methoxybenzoic acid; and 3-bromo-2-methylbenzoic were investigated using experimental and quantum chemical theoretical approach for vibrational and electronic properties from the optimized structure. Becke three parameter Lee–Yang–Parr density functionals along with 6-311++G(d,p) basis set were employed to compute their geometric optimization, fundamental frequencies and molecular parameters. The detected FT-IR and FT-Raman spectra were compared with their simulated spectra and the rms error between the detected and simulated vibrational frequencies was found at 6.17, 7.22 and 6.76 cm−1 for FMA, CMA and BMA, respectively. All the vibrational fundamentals were assigned unequivocally using potential energy distribution (PED) obtained in the computations. 1H and 13C NMR chemical shifts were evaluated by integrating the gauge-independent atomic orbital (GIAO) method with DFT and compared with corresponding experimental values. TD-DFT approach was followed to compare the simulated absorption maxima (λmax) in DMSO-d6 solvent with observed values and interpreted in terms of HOMO and LUMO. The global reactive descriptors were estimated from the associated energies of HOMO and LUMO which describe the reactivity and stability of the molecules. Molecular electrostatic potential (MEP) surface has been determined using the charge density distributions to demonstrate electrophilic and nucleophilic nature of the molecules. DFT computations also ascertained the applicability of the titled molecules as NLO materials from the computed values of dipole moment and hyperpolarizability. Thermodynamic parameters and rotational constants were also evaluated employing rigid rotor harmonic oscillator approximation. Natural bond orbital (NBO) analysis confirmed the charge delocalization due to intra-molecular interactions.

Synthesis, crystal structure, Hirshfeld surface, QTAIM, NCI-RDG, DFT and molecular docking studies of 4-(aryl)-1,4-dihydro-N,1-dimethyl-6-(methylthio)-3,5-dinitropyridin-2-amines

Two single crystals, 4-(2-ethoxyphenyl)-1,4-dihydro-N,1-dimethyl-6-(methylthio)-3,5-dinitropyridin-2-amine (EDMDA) and 4-(4-fluorophenyl)-1,4-dihydro-N,1-dimethyl-6-(methylthio)-3,5-dinitropyridin-2-amine (FDMDA) compounds have been synthesized by one pot multicomponent reaction. Single crystal X-ray diffraction (SC-XRD) technique has been utilized to determine the molecular structure of EDMDA and FDMDA compounds, which are crystalized into triclinic with P-1 and monoclinic with P1 21 C1 space group respectively. Both EDMDA and FDMDA crystal structures are stabilized by intramolecular and intermolecular N-H···O hydrogen bonding. Further, the intramolecular interactions are studied by QTAIM and NCI-RDG analysis, whereas the intermolecular interactions have been quantified by 3D Hirshfeld surface and 2D fingerprint analysis. Additionally, energy framework analysis has been determined for the title compounds and utilized to explore the individual and total interaction energy between the each molecule. Frontier molecular orbital (HOMO-LUMO) plots and molecular electrostatic potential (MEP) surface are obtained to gain more insight into the electronic properties and reactive sites of chemical species. Finally, the molecular docking studies have carried out for the title compounds with EGFR and VEGFR tyrosine kinase (PDB IDs: 4WKQ, 6JOL, 4AGC and 4AGD) receptors. The studies revealed that the ligands have a greater binding affinity with the chosen EGFR and VEGFR receptors.