Frontier Orbital Study Research Articles

Synthesis, crystal structure, spectroscopic, antidiabetic, antioxidant and computational investigations of Ethyl 5-hydroxy-1-isonicotinoyl-3-methyl-4,5-dihydro-1H-pyrazole-5-carboxylate

In this work, a novel pyrazole derivative, ethyl 5-hydroxy-1-isonicotinoyl-3-methyl-4,5-dihydro-1H-pyrazole-5-carboxylate (EIMPC) has been synthesized by condensation of ethyl 2,4-dioxopentanoate with isoniazid. Its molecular structure was characterized by FT-IR, 1H NMR, 13C NMR and ESI-MS spectroscopies and by single crystal X-ray diffraction (XRD). The experimental structure shows the presence of both enantiomeric forms and of a most stable C2 conformer while the optimized theoretical structures in gas phase and aqueous solution by functional hybrid B3LYP/6–311++G** level of theory evidence two stable C1 and C2 conformers. Both differ in the position of side chains containing the carboxylate groups. Higher repulsions between the most electronegative O atoms of side chains together with the higher volume and low dipole moment value probably justify why C1 cannot exist in the solid phase. Hydrations of acceptors and donors groups of C2 by water molecules could explain the shifting of bands assigned to those groups toward lower wavenumbers and, also, its higher solvation energy. Frontier orbitals studies support the higher reactivity of C2 in both media, as compared with C1. Comparisons between theoretical and experimental IR and NMR spectra show good correlations among them. 1H and 13C NMR chemical shifts predicted for both forms of (EIMPC) in aqueous solution suggest that C1 could also be present in this medium, as suggested by NBO and AIM calculations. 3D Hirshfeld surface and 2D fingerprint plot are carried to define the contribution of non-covalent interactions in EIMPC crystal. EIMPC was also evaluated in vitro for their α-glucosidase and α-amylase inhibition, and antioxidant activities. Thus, molecular docking analyses of the title compound were performed within the active site of α-glucosidase (PDB ID:4XP0), α-amylase (PDB ID:2QPU), oxidase (PDB ID:6I95) to analyze the binding conformation and interactions responsible for their activities.

Synthesis, structural, molecular docking and spectroscopic studies of (E)-N'-(4-methoxybenzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide

(E)-N'-4-methoxybenzylidene-5-methyl-1H-pyrazole-3-carbohydrazide (E-MBPC) has been synthesized and characterized by FT-IR, 1H & 13C NMR and ESI-MS spectroscopic methods. The (E)-configuration of hydrazonoic group was confirmed by single-crystal X-ray diffraction. Theoretical structures of E-MBPC in both gas phase and aqueous solution have been optimized by using hybrid B3LYP/6-311++G** calculations. Calculations in solution have shown that dipole moment increases from 7.97 D in the gas phase to 13.68 D in solution with solvation energy of −131.34 kJ/mol. Atomic charges have evidenced that the protonation of E-MBPC in solution could occur only in the N28 atom because those charges on this atom show negative values. Mapped MEP surfaces show that the nucleophilic sites is located on the O21 and N28 atoms including the N16 atom while the electrophilic sites are observed on the N24-H27 and N18-H19 bonds. NBO calculations support the high stability of E-MBPC in solution while frontier orbitals studies suggest low reactivity of E-MBPC in both media, as compared with the (E)-N'-(4-(dimethylamino)benzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide derivative. The vibrational assignments of 93 vibration modes expected for E-MBPC were reported together with the corresponding force fields and force constants in both media. The predicted Raman and Ultraviolet-visible spectra were also reported for E-MBPC at the same level of theory. Good correlations were obtained between the predicted 1H- and 13C NMR spectra and the corresponding experimental ones. In addition, molecular docking studies between the title ligand and 4AMJ protein were performed. Docking results revealed that the title compound can be designed as a potential anti-diabetic agent.

S(-) and R(+) species derived from antihistaminic promethazine agent: structural and vibrational studies

Structural and vibrational properties of free base, cationic and hydrochloride species derived from both S(-) and R(+) enantiomers of antihistaminic promethazine (PTZ) agent have been theoretically evaluated in gas phase and in aqueous solution by using the hybrid B3LYP/6-31G* calculations. The initial structures of S(-) and R(+) enantiomers of hydrochloride PTZ were those polymorphic forms 1 and 2 experimentally determined by X-ray diffraction. Here, all structures in aqueous solution were optimized at the same level of theory by using the polarized continuum (PCM) and the universal solvation model. As was experimentally reported, variations in the unit cell lead to slight energy, density, and melting point differences between the two forms but, this behavior is not carried through in isotropic condition, like in solution with non-chiral solvents. Hence, the N–C distances, Mulliken, atomic natural population (NPA) and Merz-Kollman (MK) charges, bond orders, stabilization and solvation energies, frontier orbitals, some descriptors and their topological properties were compared with the antihistaminic cyclizine agent. The frontier orbitals studies show that the free base species of both forms in solution are more reactive than cyclizine. Higher electrophilicity indexes are observed in the cationic and hydrochloride species of PTZ than cyclizine while the cationic species of cyclizine have higher nucleophilicity index than both species of PTZ. The presences of bands attributed to cationic species of both enantiomers are clearly supported by the infrared and Raman spectra in the solid phase. The expected 114, 117 and 120 vibration normal modes for the free base, cationic and hydrochloride species of both forms were completely assigned and the force constants reported. Reasonable concordances among the predicted infrared, Raman, UV-Vis and Electronic Circular Dichroism (ECD) with the corresponding experimental ones were found.

Structural And Vibrational Studies on Isomers of Antiviral Ribavirin Drug in Gas and Aqueous Environmental by Using The SQM Approach

Five stable isomers of antiviral ribavirin agent were theoretically determined in gas and aqueous solution by using the hybrid B3LYP/6-31G* method. Here, the solvent effects were studied with the self consistent reaction field (SCRF) methodology employing the polarized continuum (PCM) and the universal solvation model (SM). Structural, electronic and topological properties were reported for all isomers while the vibrational analyses were performed only for those two polymorphic structures experimentally observed in the solid phase by X-ray diffraction. Calculations have evidenced that C2 correspond to the polymorphic V1 structure while C5 to the polymorphic V2 structure. The high dipole moment values predicted for C2 and C5 in both media could probably explain their presences in the solid. Experimental available IR and Raman spectra of ribavirin in the solid state and normal internal coordinates were employed together with the scaled quantum mechanical force field (SQMFF) approach to perform the complete vibrational assignments in both media. Here, the 81 vibration modes expected for C2 and C5 in both media were completely assigned. The frontier orbitals studies reveal that C5 is the less reactive in both media. Here, the gap value observed for C5 is in agreement with the value recently reported for ribavirin by using B3LYP/6-311++G** calculations.

Synthesis and characterization of p-xylylenediaminium bis(nitrate). Effects of the coordination modes of nitrate groups on their structural and vibrational properties

The p-xylylenediaminium bis(nitrate) compound have been synthesized and then, it was characterized by using Fourier Transform infrared (FT-IR) in the solid phase and, by using the Ultraviolet–Visible (UV–Visible) and Hydrogen and Carbon Nuclear Magnetic Resonance (1H- and 13C-NMR) spectra in aqueous solution and in dimethylsulfoxide solvent. In this work, two monodentate and bidentate coordination modes were considered for the nitrate ligands in both media in order to study the structural and vibrational properties of that salt. Hence, the natural bond orbital (NBO), atoms in molecules (AIM), Merz-Kollman (MK) charges, molecular electrostatic potentials (MEP) and frontier orbitals studies were performed for p-xylylenediaminium bis(nitrate) and their cation and anion species taking into account for the salt those two coordination modes for the nitrate ligands. The intermolecular interactions of this salt were also evaluated by Hirshfeld surface analysis. The B3LYP calculations performed by using the hybrid method and the 6-311G* and 6-311++G** basis sets generate monodentate and bidentate structures with Ci and C2 symmetries, respectively. The force fields and the force constants values for these two structures were also computed and their complete vibrational assignments were performed by using those both levels of theory. The strong band at 1536 cm−1, the bands between 2754 and 2547 cm−1 and the bands between 1779 and 1704 cm−1 support clearly the presence of the dimeric species while the IR bands at 1986/1856 cm−1 could justify the presence of the bidentate species in the solid phase.

A structural and spectroscopic study on carquejol, a relevant constituent of the medicinal plant Baccharis trimera (Less.) DC. (Asteraceae)

Carquejol and its acetate are monoterpenoids based on the rare o-menthane skeleton and distinctive components of the essential oil from Baccharis trimera. Carquejol was characterized by using Fourier Transform infrared (FT-IR) and Raman (FT-Raman), Ultraviolet–Visible (UV–Visible), Electronic Circular Dichroism (ECD), Mass, Hydrogen and Carbon Nuclear Magnetic Resonance (1H and 13C NMR) and 2D 1H1H gCOSY, 1H13CgHSQC, 1H13CgHMBC spectroscopies. Due to the chirality of this monoterpenoid, six different structures were analysed, of which only four showed higher populations and minimal energies. The natural bond orbital (NBO), atoms in molecules (AIM), Merz-Kollman (MK) charges, molecular electrostatic potentials (MEP) and frontier orbitals studies were performed in order to evaluate their structural, electronic, topological and vibrational properties. All calculations were performed by using the hybrid B3LYP method and the 6-31G* and 6-311++G** basis sets. The comparison of the experimental ECD spectra with the corresponding theoretical ones confirm the (4S,5R) configuration assigned to carquejol. The force fields for the most stable configurations were computed by using those two levels of theory and the complete vibrational assignments for the two conformations of carquejol are reported. The different orientations and directions of the dipole moments of the two structures and the proximity in the nucleophilic indexes with those reported for other terpenes could justify in part the potential biological properties reported for carquejol. The MEP surfaces for both structures reveal that the nucleophilic and electrophilic sites of higher reactivity are principally centred on the OH groups.

Vibrational and structural study of onopordopicrin based on the FTIR spectrum and DFT calculations

In the present work, the structural and vibrational properties of the sesquiterpene lactone onopordopicrin (OP) were studied by using infrared spectroscopy and density functional theory (DFT) calculations together with the 6-31G∗ basis set. The harmonic vibrational wavenumbers for the optimized geometry were calculated at the same level of theory. The complete assignment of the observed bands in the infrared spectrum was performed by combining the DFT calculations with Pulay’s scaled quantum mechanical force field (SQMFF) methodology. The comparison between the theoretical and experimental infrared spectrum demonstrated good agreement. Then, the results were used to predict the Raman spectrum. Additionally, the structural properties of OP, such as atomic charges, bond orders, molecular electrostatic potentials, characteristics of electronic delocalization and topological properties of the electronic charge density were evaluated by natural bond orbital (NBO), atoms in molecules (AIM) and frontier orbitals studies. The calculated energy band gap and the chemical potential (μ), electronegativity (χ), global hardness (η), global softness (S) and global electrophilicity index (ω) descriptors predicted for OP low reactivity, higher stability and lower electrophilicity index as compared with the sesquiterpene lactone cnicin containing similar rings.

A Frontier Orbital Study with ab Initio Molecular Dynamics of the Effects of Solvation on Chemical Reactivity: Solvent-Induced Orbital Control in FeO-Activated Hydroxylation Reactions

Solvation effects on chemical reactivity are often rationalized using electrostatic considerations: the reduced stabilization of the transition state results in higher reaction barriers and lower reactivity in solution. We demonstrate that the effect of solvation on the relative energies of the frontier orbitals is equally important and may even reverse the trend expected from purely electrostatic arguments. We consider the H abstraction reaction from methane by quintet [EDTAH(n)·FeO]((n-2)+), (n = 0-4) complexes in the gas phase and in aqueous solution, which we examine using ab initio thermodynamic integration. The variation of the charge of the complex with the protonation of the EDTA ligand reveals that the free energy barrier in gas phase increases with the negative charge, varying from 16 kJ mol(-1) for [EDTAH4·FeO](2+) to 57 kJ mol(-1) for [EDTAHn·FeO](2-). In aqueous solution, the barrier for the +2 complex (38 kJ mol(-1)) is higher than in gas phase, as predicted by purely electrostatic arguments. For the negative complexes, however, the barrier is lower than in gas phase (e.g., 45 kJ mol(-1) for the -2 complex). We explain this increase in reactivity in terms of a stabilization of the virtual 3σ* orbital of FeO(2+), which acts as the dominant electron acceptor in the H-atom transfer from CH4. This stabilization originates from the dielectric screening caused by the reorientation of the water dipoles in the first solvation shell of the charged solute, which stabilizes the acceptor orbital energy for the -2 complex sufficiently to outweigh the unfavorable electrostatic destabilization of the transition-state relative to the reactants in solution.

Stability Analysis and Frontier Orbital Study of Different Glycol and Water Complex

A detailed theoretical study of hydrogen-bond formation in different polyethylene glycol + water complex and dipropylene glycol + water have been performed by Hartree Fock (HF) method, second-order Møller-Plesset perturbation theory (MP2), and density functional theory (DFT) using 6-31++G(d,p) basis set. B3LYP DFT-D, WB97XD, M06, and M06-2X functionals have been used to describe highly dispersive hydrogen-bond formation appropriately. Geometrical parameters, interaction energies, deformation energies, deviation of potential energy curves of hydrogen bonded O–H from that of free O–H, frontier orbitals, and charge transfer have been studied to analyze stability and nature of hydrogen bond formation of various glycol and water complexes. It is found that WB97XD is best among all the applied DFT functionals to describe hydrogen bond interaction, and intermolecular hydrogen bonds have higher covalent character and accordingly higher strength when glycol acts as proton donor for glycol + 1 water complex system.

Density functional and frontier orbital study of the physical process of the conformational isomerism of ethane

In order to explore effective theoretical parameters to follow the physical processes of the conformational isomerism, a density functional and molecular orbital study of the conformational isomerism of ethane molecule isfurnished by adopting the geometry optimization technique, GOT, The total energy, the eigen values ol the frontier orbitals, the HOMO-LUMO gap, the global hardness, the golbal softness and chemical potential have been computed as a function of torsional angles of the internal rotation of the molecule. The eigen values of the frontier orbitals, the HOMO-LUMO gap, the global hardness and global softness are found to follow the physical process of evolution of the molecular conformations due to unrestricted rotation around single bonds in a molecule. A comparative study of the nature of the profiles of the eigen values of the frontier orbital and the density functional parameters with the potential energy diagram explores the potential ability of the molecular orbital and density functional parameters to study and compute the physical process of the conformational isomerism of the molecule.

Frontier orbital study on the 4-hydroxybenzoate-3-hydroxylase-dependent activity with benzoate derivatives.

Based on molecular orbital computer calculations the present paper provides a new hypothesis for catalytic characteristics of 4-hydroxybenzoate-3-hydroxylase (EC 1.14.13.2). A clear correlation between in kcat for the conversion of a series of 4-hydroxylated substrates and their E(HOMO) leads to the hypothesis that Frontier orbital HOMO characteristics [E(HOMO) and HOMO density on C3] of the substrates are the predominant factor in regulating the fate of a benzoate derivative at the active site of the enzyme. The HOMO characteristics can be used to explain whether a compound will be converted by the enzyme or merely acts as an effector. Furthermore, the hypothesis provides quantitative theoretical support for a catalytic mechanism in which the substrate reacts in its dianionic form and for a mechanism in which the electrophilic attack of the C(4a)-peroxyflavin, or of the hydroxyl radical derived from it, on the benzoate dianion is the rate limiting step in catalysis at pH 8, 25 degrees C. Finally, it is demonstrated that the hypothesis can be used as a basis for the formulation of working hypotheses in future research, investigating the conversion and regioselective orientation of the various possible substrates in the active site of the wild-type 4-hydroxybenzoate-3-hydroxylase, its mutants as well as of various other flavin-dependent aromatic hydroxylases, such as for example 3-hydroxybenzoate-4-hydroxylase (EC 1.14.13.23), 3-hydroxybenzoate-6-hydroxylase (EC 1.14.13.24) and phenol hydroxylase (EC 1.14.13.7).

ChemInform Abstract: Binding of Alkenes to the Ligands in OsO2X2 (X: O and NR) and CpCo(NO)2. A Frontier Orbital Study of the Formation of Intermediates in the Transition‐Metal‐Catalyzed Synthesis of Diols, Amino Alcohols, and Diamines.

Chemischer InformationsdienstVolume 17, Issue 32 Physical Organic Chemistry ChemInform Abstract: Binding of Alkenes to the Ligands in OsO2X2 (X: O and NR) and CpCo(NO)2. A Frontier Orbital Study of the Formation of Intermediates in the Transition-Metal-Catalyzed Synthesis of Diols, Amino Alcohols, and Diamines. K. A. JOERGENSEN, K. A. JOERGENSENSearch for more papers by this authorR. HOFFMANN, R. HOFFMANNSearch for more papers by this author K. A. JOERGENSEN, K. A. JOERGENSENSearch for more papers by this authorR. HOFFMANN, R. HOFFMANNSearch for more papers by this author First published: August 12, 1986 https://doi.org/10.1002/chin.198632076AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume17, Issue32August 12, 1986 RelatedInformation

Binding of alkenes to the ligands in OsO2X2 (X = O and NR) and CpCo(NO)2. A frontier orbital study of the formation of intermediates in the transition-metal-catalyzed synthesis of diols, amino alcohols, and diamines

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBinding of alkenes to the ligands in OsO2X2 (X = O and NR) and CpCo(NO)2. A frontier orbital study of the formation of intermediates in the transition-metal-catalyzed synthesis of diols, amino alcohols, and diaminesKarl Anker. Joergensen and Roald. HoffmannCite this: J. Am. Chem. Soc. 1986, 108, 8, 1867–1876Publication Date (Print):April 1, 1986Publication History Published online1 May 2002Published inissue 1 April 1986https://doi.org/10.1021/ja00268a026RIGHTS & PERMISSIONSArticle Views478Altmetric-Citations92LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1018 KB) Get e-Alerts Get e-Alerts

A frontier orbital study of substituent effects in the deamination of N-substituted quinone di-imines

The substituent effects on the rate constants of the acid and alkaline deamination of quinone di-imines are explained, using the frontier orbital (FO) perturbation theory. The main contributions to the perturbation energy are electrostatic and orbital interactions. The alkaline deamination is both orbital and charge controlled, whereas the acid deamination is only an orbital-controlled reaction.