Electrophilic Sites Research Articles

Computational Analysis on Molecular Stability and Binding Affinity of 3-(Aminothiazolyl)Quinolone Derivative as Multitargeting Antibacterial Agents through Ab Initio Methods and Molecular Docking

The present study deals with the application of ab initio method using density functional theory (DFT) at M06-2X/6-311++G(d,p) to characterize the considered molecule completely. Though the anti-bacterial activity of the 3-(amino thiazolyl)quinolone derivatives was studied, the effects of intermolecular hydrogen bonding on chemical and biological processes remain unexplored or have not been thoroughly investigated so far. Investigations into non-covalent interactions were carried out using the reduced density gradient methodology and the quantum theory of atoms in molecules. An electron localization function was used to investigate the electronic vicinity of each atom in a molecule. Natural bond orbital analysis was used to determine the correlated stabilization energies for the intermolecular hydrogen bonds (H-bonds) that are responsible for the molecular stability of the dimer structure. The electrophilic and nucleophilic sites were predicted using the molecular electrostatic potential. The density of states and partial density of states were also used to represent the frontier molecular orbitals. The inhibitory activities of the compound with different classes of bacteria were also investigated using molecular docking simulation.

Quantitative Determination of Water in Organic Liquids by Ambient Mass Spectrometry

AbstractThis study uses a rapid tandem mass‐spectrometry method to determine water content in complex organic solutions. Emphasis is placed on trace‐water analysis by a fast and accurate alternative to the Karl–Fischer method. In this new method, water is captured by a charge‐labeled molecular probe. Water binds strongly with high specificity to the strongly electrophilic aldehyde site in a charge‐labelled molecule (N‐methylpyridinium); competitive binding by other analytes is effectively discriminated against in the mass‐measurement step. Quantitative determinations are made over a wide concentration range, 0.001 % (10 ppm) to 99 %, with better than 10 % relative standard deviation, along with short (1 min) analysis times using small sample volumes (several μL). Applications include water measurement in simple organic solvents, for example, deuterated solvents, as well as in complex mixtures, for example, organic reaction mixtures. Additionally, this method allows for water monitoring in levitated droplets. Mechanistic investigations into the impact of water on important chemical processes in organic synthesis and environmental science are reported.

Quantitative Determination of Water in Organic Liquids by Ambient Mass Spectrometry.

This study uses a rapid tandem mass-spectrometry method to determine water content in complex organic solutions. Emphasis is placed on trace-water analysis by a fast and accurate alternative to the Karl-Fischer method. In this new method, water is captured by a charge-labeled molecular probe. Water binds strongly with high specificity to the strongly electrophilic aldehyde site in a charge-labelled molecule (N-methylpyridinium); competitive binding by other analytes is effectively discriminated against in the mass-measurement step. Quantitative determinations are made over a wide concentration range, 0.001 % (10 ppm) to 99 %, with better than 10 % relative standard deviation, along with short (1 min) analysis times using small sample volumes (several μL). Applications include water measurement in simple organic solvents, for example, deuterated solvents, as well as in complex mixtures, for example, organic reaction mixtures. Additionally, this method allows for water monitoring in levitated droplets. Mechanistic investigations into the impact of water on important chemical processes in organic synthesis and environmental science are reported.

Photophysical properties of four-membered BN3 heterocyclic compounds: theoretical insights.

Understanding the photochemistry of boron nitrogen (BN)-containing compounds is an important aspect to enhance the various optical and electronic applications. In this work, we have explored the structure, bonding, reactivity, electronic absorption (UV-Vis), and light harvesting efficiency (LHE) of a series of BN3 ring and open-chain systems. The frontier molecular orbitals (FMO) analysis found that ring systems have a low HOMO-LUMO energy gap as compared to the open-chain systems which insinuates the feasibility of ring systems in the optoelectronic materials. Also, the molecular electrostatic potential (MEP) maps have been computed to pursue the electrophilic and nucleophilic sites available at the surface of the compound. Interestingly, we have found that the open-chain compounds show more molecular charge distribution range rather than the ring compounds. The investigation of photophysical properties showed that the UV-Vis absorption significantly red-shifted in BN3 ring systems as compared to open-chain counterparts. Furthermore, light harvesting efficiency (LHE) was also found higher in the ring systems as compared to the BN3 open-chain systems. Moreover, the computed structural parameters are found well corroborated with the available X-ray data. Structures of all compounds were optimized by using density functional theory (DFT) method, with M06-2X/6-31G(d,p) level. All the calculations in this work are carried out in Gaussian 16 program package. GaussView6.1 software was used for the modeling of initial geometries and for the plotting of MEP plots. To account the solvent effect on geometries the polarized continuum model (PCM) was used and tetrahydrofuran (THF) taken as solvent. The NBO6.0 program (incorporated in G16 software) was used for the exploration of bonding nature and stabilization energies of B-N bond. The absorption spectra were simulated by using ORCA 4.2 program.

RETRACTED: Molecular structure solvent–solute, electronic, topology and dynamics simulation studies on 2-[[1-(cyclopropyl methoxy)-4-hydroxy-2-oxoquinoline-3-carbonyl] amino] acetic acid-an effective CKD drug

The current theoretical work analyzes the optimal structure and vibrational assignments of 2-[[1-(cyclopropyl methox)-4-hydroxy-2-oxoquinoline-3-carbonyl] amino] acetic acid (2C2O), examined theoretically through DFT method. PED values were calculated, and vibrational assignments have been determined. Studies employing FT-IR and FT-Raman methods were explored in both experimental and theoretical scenarios. By using Gaussian 09W, structural optimization, and bond parameters are examined. MEP differentiates nucleophilic and electrophilic sites and establishes a molecules 3-dinemsional charge distribution using gas and solvent phases. Global descriptors and band gap energies are provided using the Frontier Molecular Orbital(FMO) study. The electron delocalization resulting from hyperconjucation can be understood by using the NBO method. The TD-DFT technique and IEFPCM model were utilized to stimulate the UV spectra of the title compound. FUKUI function used to trace the area of reactive sites. Topological explorations were scrutinized using the Multiwave function. The title chemical exhibits a promising pharmacological profile. In this research, we assess its bioactivity and drug likeness. Molecular docking using Autodock technique reveals the compounds inhibiting effect on receptors. Analysis of the protein–ligand complexes stability was done using MD simulations.

Molecular configuration, electronic properties, reaction activity of metal-free naphthalocyanine under the external electric field

This work presents a regulation effect of external electric fields on geometric structures, polarisability and reaction activity of metal-free naphthalocyanine (H2Nc). In particular, EEF more than 0.015 a.u.(0.77 V/Å) will bend two pairs of opposing molecular arms (naphthalene subunits) to the x-positive and x-negative directions of the planar molecule. Flipping the EEF direction flips also the bending direction of molecular arms. Furthermore, when the EEF is removed, the molecule can be restored to the planar structure. EEF can induce a significant dipole moment transformation (magnitude and direction of the dipole moment), reduce LUMO-HOMO gap of H2Nc, enhance the first hyperpolarizability from 0 to a significant amount, and change the distribution of electrophilic or nucleophilic reaction sites and enhance reactivity of H2Nc. EEF can be used to regulate the structure transformation and properties of H2Nc, which can promote the potential application of H2Nc such as molecular devices or chemical reactions.

The experimental and theoretical spectroscopic elucidation of molecular structure, electronic properties, thermal analysis, biological evaluation, and molecular docking studies of isococculidine

Experimental techniques, such as vibrational spectroscopy (FT-IR and FT-Raman), UV–visible, thermal analysis (DSC), along with quantum chemical calculations based on density functional theory (DFT) were conducted to explore the physicochemical properties of a plant-derived natural product, isococculidine. The potential energy distribution (PED) has been assigned to each of the vibrational bands observed in FT-IR and FT-Raman spectra. The reduced density gradient (RDG) analysis was used to demonstrate the non-covalent interactions (NCI). Natural bond orbital (NBO) study revealed that the benzene ring's hyper-conjugative interactions were primarily responsible for the molecular stability. The intramolecular charge transfer has been further verified by the HOMO-LUMO analysis. The molecular electrostatic potential (MEP) analysis signifies that the nucleophilic and electrophilic interaction sites are prone to oxygen of O1-CH3 and hydrogens of O2-CH3, respectively. The chemical activity and the toxicity of the molecule have been examined based on the calculated Mulliken charges, softness, hardness, and local reactivity parameters. The thermal properties like specific heat capacity, entropy and enthalpy which affect the drug's activities were studied. The large value of the first hyperpolarizability indicates its significant nonlinear optical (NLO) property. The molecular docking of isococculidine has been performed with nicotinic acetylcholine protein which deliberates the significant biological activity of the molecule.

Quantum computations of non-steroidal anti-inflammatory drug molecules using Density Functional Theory

This paper addresses the electronic states and physicochemical properties of non-steroidal anti-inflammatory drug (NSAID) namely: Ibuprofen, Ketoprofen and Flufenamic acid. The molecular structures are quantum chemically treated and geometrically optimised using density functional theory (DFT). The computed geometrical parameters are compared with the experimental data. The Mulliken charge analysis is accomplished to understand the partial charge distribution in molecules. The molecular electrostatic potential analysis has been used to identify the appropriate location for an electrophilic and nucleophilic attacking site. Frontier molecular orbitals of the molecules are estimated and analysed. The HOMO-LUMO energy gaps have been used to estimate the different global reactivity descriptors of the selected molecules under investigation. The FT-IR spectra of molecules are recorded experimentally and are computed using DFT. The potential energy distribution (PED) assignment for the computed vibrations is carried out. The NBO analysis has been used to find the most intensive interaction in molecules based on the Fock-matrix sta3bilization energy. The NLO parameters have been computed for molecules to check their suitability towards NLO based applications. The UV-absorption spectra and ADME parameters for titled molecules are also simulated.

The role of P2O5 on the stability of β-C2S in AOD slag based on the improvement of hydration activity

The original AOD slag in the cold state contained more than 50 wt% low-hydration activity γ-C2S, which significantly affects the hydration activity. Therefore, the effect of the typical crystal stabilizer P2O5 on the formation of a new phase and the enhancement in the mass fraction of high hydration activity β-C2S in AOD slag were studied, and the internal factors that controlled the doping preference and influenced the hydration activity of the crystal stabilizer P2O5 were revealed. When the addition of P2O5 was 0.6 wt%, the mass fraction of β-C2S in AOD slag was increased by 50.8 wt%. The P5+ and its oxide P2O5 entered the lattice of C2S in solid solution, causing lattice distortion. After P doping, the charge energies of the Ca, Si and O atoms shifted toward the low energy direction by approximately 5 eV, which increased the stability of the electronic structure. In addition, P doping changed the delocalization of the CBM in the pure phase, partially located the LDOS of the VBM and CBM, and increased the numbers of nucleophilic and electrophilic attack sites, thus improving the hydration activity of β-C2S.

Highly selective regeneration of 1,4-NADH enabled by a metal-free core-shell photocatalyst of resorcinol-formaldehyde resins@polyaniline under visible light

Cofactors, including reduced nicotinamide adenine dinucleotide (NADH), are involved in approximately 80 % of oxidoreductase-catalyzed reactions. However, NADH has not been widely used in the industrial production processes due to cost factors. In this work, we have designed a kind of metal-free core-shell photocatalyst with resorcinol-formaldehyde resin spheres as the core and polyaniline as the shell (RF@PANI) for the highly efficient and selective photocatalytic regeneration of 1,4-NADH (only 1,4-NADH has enzyme activity). It was demonstrated that the introduction of the carbonyl group and the sum of electronic effects made the C4 site of NAD+ a more electrophilic hydride transfer site rather than C6 and C2 in the RF@PANI system, leading to the high selectivity of NAD+ to 1,4-NADH. The discovery of this mechanism will guide the design of more efficient and highly selective catalysts to break through the cost limitations for the large-scale applications of NADH.

Theoretical investigations on structural, spectral, NBO, NLO and topology exploration (AIM, ELF, LOL, RDG) of piperazine-2,5-dione oxalic acid monohydrate

The present work investigates the structural stability and nonlinear optical (NLO) activity of piperazine-2,5‑dione oxalic acid monohydrate (PDOAH) using quantum chemical computational techniques. The optimized molecular structure and vibrational wavenumbers of the PDOAH molecule are determined by density functional theory (DFT) with B3LYP/6–311G(d,p) basis set. The vibrational wavenumbers, IR intensities, Raman activities and their corresponding PED values are obtained and analysed. Natural bond orbital (NBO) analysis is carried out to determine inter and intramolecular charge transfer interaction, intermolecular hydrogen bonding and hyperconjugative interactions that stabilize the structure. The charge transfer interaction, electrophilic, nucleophilic and chemical reactivity sites are identified with the aid of molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analysis. The TD-DFT method is utilized in UV–Vis spectral analysis for the molecule in the water solvent. RDG and IRI analysis is performed to spot the van der Waals interaction and steric effect within the molecule. The Hirshfeld surface analysis is carried out to scrutinize the intermolecular interactions. The nonlinear optical (NLO) parameters of PDOAH are evaluated through DFT calculation and compared with that of urea.

Evaluation of physico-chemical parameters of some psychoactive compounds based on molecular modeling

In this paper we have evaluated from a physico-chemical point of view some psychoactive compounds representing substituted phenethylamines which contain methoxy groups on the 2 and 5 positions of a benzene ring. The chemical potential of the investigated compounds was assessed by computing of the main quantum molecular descriptors, such as the dipole moment, the energy of the highest/lowest occupied/unoccupied molecular orbital, the gap energy, the electronegativity, the chemical hardness/softness, the electrophilicity index etc. Also, the presence of the nucleophilic and electrophilic sites was identified by using the molecular electrostatic potential diagram.

Spectroscopic, quantum chemical investigation and molecular docking studies on N-(2-benzoylamino) phenyl benzamide: A novel SARS-CoV-2 drug.

The present work describes the structural and spectral properties of N-(2-benzoylamino) phenyl benzamide (NBPB). The geometrical parameters of NBPB molecule such as bond lengths, bond angles and dihedral angles are calculated and compared with experimental values. The assigned vibrational wave numbers are in good agreement with the experimental FTIR and FT Raman spectra. The vibrational frequency of C=O stretching was downshifted to a lower wave number (red shift) due to mesomeric effect. The UV-Vis spectrum of the title compound was simulated and validated experimentally. The energy gap and charge transfer interaction of the title molecule were studied using frontier molecular orbital analysis. The electrophilic and nucleophilic reactivity sites of NBPB were investigated through the analysis of the molecular electrostatic potential surface and the Fukui function. An assessment of the intramolecular stabilization interactions of the molecule was performed using natural bond orbital analysis. The drug-likeness parameter was calculated. To investigate the inhibitory potential of the molecule, molecular docking analysis was conducted against SARS-CoV-2 proteins, revealing its capability to serve as a novel inhibitor against SARS-CoV-2. The high binding affinity of NBPB molecule was due to the presence of hydrogen bonds along with different hydrophobic interactions between the drug and the SARS-CoV-2 protein receptor. Hence, the title molecule is identified to be a potential candidate for SARS-CoV-2.

Spectroscopic investigations, quantum chemical, molecular docking and drug likeness studies of t-butyl-3,4,5-trimethyl-2-pyrrole carboxylate

The geometrical structure of t‑butyl‑3,4,5-trimethyl-2-pyrrole carboxylate (TBTPC) was computed by DFT calculations using the B3LYP method and the 6–311++G(d,p) basis set using the Gaussian 09 software. Vibrational wavenumbers were assigned using the VEDA 4.0 program. Natural bond orbital (NBO) analysis predicts the hyper-conjugative interaction and stabilization interaction of the TBTPC compound. HOMO, LUMO, and other molecular properties were calculated. The density of states (DOS) spectrum was also predicted. The ultraviolet-visible spectrum has been experimentally and theoretically validated and simulated. The electrophilic and nucleophilic reactive sites of the TBTPC molecule were determined using the Fukui function calculation and the molecular electrostatic potential (MEP) surface. Molecular docking analysis of the TBTPC ligand helps to investigate its inhibitory nature against Lysine-specific demethylase 1A (LSD1), α-amylase, BCL-1, and monoamine oxidase (MAO). From the molecular docking results, TBTPC has promising inhibition activity against gastric cancer.

Applicability of transferable multipole pseudo-atoms for restoring inner-crystal electronic force density fields. Chemical bonding and binding features in the crystal and dimer of 1,3-bis(2-hydroxyethyl)-6-methyluracil.

We considered it timely to test the applicability of transferable multipole pseudo-atoms for restoring inner-crystal electronic force density fields. The procedure was carried out on the crystal of 1,3-bis(2-hydroxyethyl)-6-methyluracil, and some derived properties of the scalar potential and vector force fields were compared with those obtained from the experimental multipole model and from the aspherical pseudo-atom model with parameters fitted to the calculated structure factors. The procedure was shown to accurately replicate the general vector-field behavior, the peculiarities of the quantum potentials and the characteristics of the force-field pseudoatoms, such as charge, shape and volume, as well as to reproduce the relative arrangement of atomic and pseudoatomic zero-flux surfaces along internuclear regions. It was found that, in addition to the quantum-topological atoms, the force-field pseudoatoms are spatially reproduced within a single structural fragment and similar environment. In addition, the classical and nonclassical hydrogen bonds in the uracil derivative crystal, as well as the H...O, N...O and N...C interactions in the free π-stacked dimer of the uracil derivative molecules, were studied using the potential and force fields within the concepts of interatomic charge transfer and electron lone pair donation-acceptance. Remarkably, the nitrogen atoms in the N...O and N...C interactions behave rather like a Lewis base and an electron contributor. At the same time, the hydrogen atom in the H...O interaction, being a Lewis acid, also participates in the interatomic electron transfer by acting as a contributor. Thus, it has been argued that, when describing polar interatomic interactions within orbital-free considerations, it makes more physical sense to identify electronegative (electron occupier) and electropositive (electron contributor) atoms or subatomic fragments rather than nucleophilic and electrophilic sites.

Yeni Bir Schiff Bazı Molekülüne in Siliko Tıbbi ve Hesaplamalı Yöntemlerle Bir Bakış

In this study, the synthesis and characterization of a new Schiff base molecule, (E)-1-(5-nitro-2-(piperidin-1-yl) phenyl)-N-(4-phenoxyphenyl) methanimine, were aimed. In addition, the molecular surface area, crystalline structure, intermolecular forces, electronic and spectroscopic properties of the molecule were investigated. Docking studies were also performed on the active sites of the main protease (Mpro) of SARS-CoV-2, and the docking result was compared with the efficacy of the native ligand N3 inhibitor. The main findings for the title molecule can be summarized as follows: The space group is P-1 and it crystallizes in the triclinic system. The unit cell consists of two monomeric units (Z=2). There are strong electrophilic attack sites in the molecule, but nucleophilic centers have low efficiency. According to the FMO analysis, the title compound is a soft, kinetically and chemically unstable and highly reactive material. The value of the binding free energy calculated by docking experiments (-9.28 kcal mol-1) is lower than that of the native inhibitor (-7.11 kcal/mol) and thus can be considered as a potential inhibitor candidate for the main protease of SARS-CoV-2.

Cg…Cg interactions driven 1D polymeric chains bridged by lattice solvents in N3-(2-pyridoyl)-4-pyridinecarboxamidrazone Pb(II) complex

This study will shed light on the non-covalent interactions present in the N3-(2-pyridoyl)-4-pyridinecarboxamidrazone Pb(II) complex [(L)Pb(CH3OH)(H2O)2] and their significance in the context of crystal packing and material properties. The complex was synthesized and characterized using single crystal X-ray structural analysis, providing valuable insights into its molecular structure. Our focus was on analyzing the non-covalent interactions in the crystal structure, where these interactions played a crucial role in the formation of one-dimensional network chains observed in the crystal. To quantitatively analyze these interactions, we employed Hirshfeld surfaces analysis. Furthermore, we performed density functional theory computational studies to calculate the molecular geometry and global reactive parameters, allowing us to gain a better understanding of the properties of the novel molecule. The molecular electrostatic potential was plotted to visualize the charge distribution and identify the electrophilic and nucleophilic sites in the molecule. Finally, we explored the non-covalent interactions and electron charge density distribution using the QTAM and NCI models, providing further insights into the complex's behavior. This study contributes to the understanding of non-covalent interactions in the context of crystal growth and design, and expands the knowledge of the structural and electronic properties of the N3-(2-pyridoyl)-4-pyridinecarboxamidrazone Pb(II) complex.

Estimation of dipole moments by Solvatochromic shift method, spectroscopic analysis of UV–Visible, HOMO-LUMO, ESP map, Mulliken atomic charges, NBO and NLO properties of benzofuran derivative

Solvatochromic shift method has been used to estimate ground state (μg) and excited state (μe) dipole moments of benzofuran derivative (5NFMOT) at room temperature indifferent solvents. This method involves Lippert, Bakhshiev and Kawski-Chamma-Viallet equations. Reichardt microscopic solvent polarity parameter was used to calculate the change in dipole moment. Effect of solvents on absorption and fluorescence spectra was investigated using Kamlet and Catalan's MLR approach. Computational studies of benzofuran derivative were carried out using Gaussian 16. Geometry optimization was performed using DFT method at 6–311++G (d, p)/B3LYP basis set. UV–Visible spectra have been studied by using TD-DFT method for the same basis set. The μg was obtained from DFT method, whereas μe from TD-DFT method. It has been observed that both from experimentally and theoretically the ground state dipole moment is higher than the excited state dipole moment. HOMO-LUMO surfaces and Mulliken atomic charges have been studied in gas phase and solution. Furthermore, 3D plots of electrostatic potential map are used to identify reactive centers such as electrophilic and nucleophilic sites. NBO analysis is helpful to obtain stability and charge delocalization of the title molecule. Polarizablity, and hyper polarizability values were used to study the NLO properties.

Potentiality of Organosulfur Compounds Against SARS-CoV-2-Coinfected Bacteria Streptococcus pyogenes and S pneumoniae: A Cross-Platform Analysis from Computational Chemistry

Objective SARS-CoV-2 coinfection with Streptococcus pyogenes and S pneumoniae increases disease severity, thus deserving more in-depth understanding. Methods The potential of garlic extract against the bacteria has been theoretically examined and extended to synergic predictions on SARS-CoV-2 Delta and Omicron variants. Results Gas chromatography–mass spectrometry characterized five main components in the extract: benzeneacetaldehyde (A1; 5.65%), diallyl disulfide (A2; 19.27%), 1-allyl-3-methyltrisulfane (A3; 21.30%), methyl salicylate (A4; 7.49%), and diallyl trisulfide (A5; 39.26%). Bioassay-based inhibition zones were 8 ± 2 mm, and MIC values 64 mg·mL−1 ( S pneumoniae) and 128 mg·mL−1 ( S pyogenes). Density functional theory suggested the organosulfur components as the most promising inhibitors with electrophilic sites at their sulfur atoms. Molecular docking simulation agreed with their potential against S pneumoniae/ S pyogenes luxS proteins and Delta/Omicron SARS-CoV-2 spike proteins, given by all docking score values being <−13 kcal·mol−1. QSARIS and ADMET predicted their bio- and pharma-favored properties. Conclusion The consistency of a variety of computational outputs justifies the dietary–supplemental potential of garlic essential oil based on its organosulfur ingredients.

Crystal structure, Hirshfeld surface analysis, and computational study of tin (IV) complex: Insights from spectroscopic, anticancer and cytotoxic properties

The complex di(p-methylbenzyl) (dibromo)(4,7-diphenyl-1,10-phenanthroline) tin (IV) complex (B1) was synthesized and characterized. For the theoretical investigation, we used DFT. With the help of the Multiwfn software package, topological analysis and RDG were calculated. A very low energy gap (2.3 eV) was observed in the HOMO-LUMO analysis. Nucleophilic and electrophilic attacking sites are confirmed using the MEP study. In a single crystal, analysis confirmed the octahedral shape and monoclinic space group. The intramolecular hydrogen was formed through the C—H—Br. The tin atom is in a uniform octahedral shape, which can be seen in the XRD of the complex B1. The Vero and Hela cell lines are used for anticancer and cytotoxic activities. Our synthesized complex shows better activity against Vero and Hela cell lines when compared to cisplatin.