Chemical Shift Values Research Articles

Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products

AbstractForrestiacids A (1) and B (2) are a novel class of [4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii, an endangered member of the Asian Douglas Fir Family. The intermolecular hetero‐Diels–Alder adducts feature an unusual bicyclo[2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X‐ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC50s <5 μM) of ATP‐citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL‐related diseases with strong links to traditional medicines.

Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products.

Forrestiacids A (1) and B (2) are a novel class of [4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii, an endangered member of the Asian Douglas Fir Family. The intermolecular hetero-Diels-Alder adducts feature an unusual bicyclo[2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X-ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC50 s <5 μM) of ATP-citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL-related diseases with strong links to traditional medicines.

Davidones F and G, Two Novel Flavonoids from Sophora davidii (Franch.) Skeels.

An unprecedented novel flavanone davidone F (1) with a seven-membered ring side chain, and a novel flavanonol davidone G (2), along with 11 known flavonoids, were isolated from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. Their planar structures were established by UV, IR, HRESIMS, 1D and 2D NMR data. The relative configurations of 1 and 2 were determined by calculation of NMR chemical shift values, the absolute configuration of 1 and 2 were assigned by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Moreover, compounds 1–13 were screened for the translocation activity of glucose transporter 4 (GLUT-4), and the fluorescence intensity was increased to the range of 1.56 and 2.79 folds. Compounds 1 and 2 showed moderate GLUT-4 translocation activity with 1.64 and 1.79 folds enhancement, respectively, at a concentration of 20 μg/mL.

Role of heteroatoms and substituents on the structure, reactivity, aromaticity, and absorption spectra of pyrene: a density functional theory study

Abstract Effect of heteroatoms viz. BN and substituents viz. –Me (methyl), –OH (hydroxyl), –NH2 (amine), –COOH (carboxyl), and –CN (cyano) on the structural parameters, global reactivity, aromaticity, and UV-visible spectra of pyrene are studied with the help of density functional theory (DFT). Global reactivity parameters such as global hardness (η) and electrophilicity (ω) are calculated using density functional reactivity theory (DFRT). Time dependent density functional theory (TD-DFT) is explored for interpreting the UV-visible absorption spectra. Aromaticity of the pyrene rings are predicted from the nucleus independent chemical shift (NICS) values. Presence of BN unit and substituent induces reasonable impact on the studied parameters. The observed absorption spectra lie predominantly within the UV-region (both blue and red shifts are observed in presence of BN and substituent). HOMO energy and absorption spectra are affected nominally in solvent phase.

Synthesis, characterization, theoretical studies and antimicrobial activity of novel 1-(2‑hydroxy-4-propoxy-3-propylphenyl)ethanones bearing thiotetrazole

We report herein a joint experimental and theoretical investigation on the novel 1-(2-hydroxy-4-propoxy-3-propylphenyl)ethanone bearing 1-propyl-1H-tetrazol-5-thiol and 2-propyl-2H-tetrazole-5-thiol pharmacophores. In the experimental studies, 1-[4-(3-((1-propyl-1H-tetrazol-5-yl)thio)propoxy)-2-hydroxy-3-propylphenyl]ethanone and 1-[4-(3-((2-propyl-2H-tetrazol-5-yl)thio)propoxy)-2-hydroxy-3-propylphenyl]ethanone were synthesized and characterized by ATR-FTIR, 1H NMR, 13C-APT, and HRMS. In the theoretical studies, the most stable conformations, vibrational and NMR spectra of these compounds were predicted by Quantum chemical calculations. Quantum chemical calculations were performed using the B3LYP functional with 3–21 G, and 6–311++G(d,p) basis sets. All quantum chemical calculations were utilized Gaussian 16 software. While torsional barriers of the compounds were determined by B3LYP/ 3–21 G, their geometry optimizations were performed by B3LYP functional with 3–21 G, and 6–311++G(d,p) basis sets. The harmonic vibrational frequencies, potential energy distribution (PED) and infrared intensities were predicted using the B3LYP/6–311++G(d,p). Theoretically predicted vibrational frequencies were compared with experimental results. Predicted NMR chemical shifts were obtained by the GIAO method using the B3LYP/6–311++G(d,p). The 1H and 13C experimental chemical shifts are consistent with the theoretical NMR chemical shift values. Antimicrobial activities of the title compounds were investigated against five bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Stenotrophomonas maltophilia) and two fungal strains (Candida albicans, Aspergillus fumigatus). The compounds showed good antimicrobial activity and inhibited all tested bacteria and fungi.

Density functional estimation of hydride and proton affinities of substituted allenes and heteroallenes

AbstractThe hydride affinity (HA) of 20 allene and heteroallene derivatives containing unsaturated rings such as cyclopentadiene (CP) ring has been computationally investigated using the B3LYP/6‐311++G(3df, 2p) method. The interaction of hydride ion (H−) with the central sp1 carbon of the designed molecules containing electron‐withdrawing groups on the CP ring has been highly desirable, and their HA values were obtained in the range of 369–788 kJ/mol. The aromaticity of CP anion has the key role in the HA increasing and its stability. The harmonic oscillator model of aromaticity (HOMA) and nucleus‐independent chemical shifts (NICS) values associated with the CP ring were calculated and compared before and after the interaction with H−. The calculated data indicated a sharp increase in HOMA and NICS indices for the anions. In the following, the protonation of three designated allenes containing a cyclopropene or cycloheptatriene and a CP ring was also investigated using the density functional theory calculations. Electrostatic potential maps for some key structures were also used for charge distribution analysis.

The detection, purity and structural properties of partially soluble mushroom and cereal β-D-glucans: A solid-state NMR study

β-D-glucans are proposed to have many health benefits. It is therefore important to have methods which can distinguish these from other carbohydrates present in natural products, as well as giving glucan content and structural information. Correlations between features in the CP/MAS spectra of β-D-glucans and enzyme assay determined β-D-glucan content were generally found to be poor. The β-D-glucan in dry and hydrated forms of the mushroom Ganoderma lucidum was investigated in detail by spectral peak fitting to the anomeric carbon C1 region in CP/MAS NMR spectra. Hydrated samples gave spectra with enhanced resolution and suggested that a clear distinction between β-D-glucans and other carbohydrates could be possible in the anomeric carbon C1 region. Chemical shift values for a range of carbohydrate polymers, which can be found alongside β-D-glucans, as well as the values for various linkages are given. Contamination by other carbohydrates and buffer salts is discussed.

Vibrational, electronic and reactivity insight on (5-chloro-benzofuran-3-yl)-acetic acid hydrazide: A Spectroscopic and DFT approach

Extensive quantum chemical calculation have been carried out to examine the Fourier Transform Infrared(FT-IR), Fourier Transform Raman(FT-Raman) and Nuclear magnetic resonance(NMR) spectra of (5-chloro-benzofuran-3-yl)-acetic acid hydrazide (5CBAH) molecule. The Gaussian computations have been carried out by DFT method using B3LYP/6-311++G (d, p) basis sets. The fundamental vibrational frequencies and intensities of the vibrational bands are analysed with the help of optimized structure. The theoretical NMR chemical shift values have been obtained using gauge independent atomic orbital (GIAO) method. The computed band gap energy of HOMO and LUMO depicts that charge transfer existed within the molecule. The internal molecular electronic interactions and their stabilizing energies are identified by the NBO analysis. The MEP map analysis is conducted to determine the chemical reactive site of the molecule. The thermodynamic properties of the title compound are studied for different temperatures. Non-linear optical properties and Fukui activity are also performed. The electron distribution and reactive site on the surface of the molecule are analyzed using ELF and LOL analysis. Atoms in Molecule (AIM) analysis is used to study the nature of interactions in molecular structure and to categorize and recognize the bonding interactions on the basis of quantum mechanical properties. The noncovalent interaction (NCI) analysis provides the most important interaction information's such as van der Waals interactions, hydrogen bonds and steric interactions present in the molecule.

Isolation and Characterization of Secondary Metabolite from the Stem Bark Extract of Allophylus africanus Beauv (Sapindaceae)

Isolation of secondary metabolites from the stem bark of Allophylus africanus Beauv (Sapindaceae) was carried out. The plant has a wide distribution in West Africa, with Nigeria (Mambila Plateau, Calabar) inclusive. It has been used in communities for both its medicinal and economic importance. The stem bark of A. africanus was extracted by percolation using chloroform as solvent and concentrated by evaporation at room temperature. Single spot with an Rf value of 0.87 was obtained at a solvent mixture of hexane: chloroform at ratio 2:8 from finger column chromatography . Characterization using spectra analysis which include FT-IR, 1H-NMR, 13C-NMR, H-H COSY, H-C COSY, 135 DEPT and mass spectroscopy. Spectroscopic studies of A. Africanus stem bark extract led to the elucidation of the structure of the compound. FT-IR spectrum indicates that the compound is an aromatic derivative. Aromatic protons where seen at the 1H-NMR chemical shift values of 7.25 ppm. Olefinic protons at 5.124, 5.146 and 6.162 ppm appeared as doublets of doublets of doublets. The compound 1-((E)- 7(((1E,5E)-6-((2,3-dimethyl-4-(((E)-3,4,5,6-tetramethyldeca-7,9-dien-2-yl)oxy)pentyl)oxy)-3,4- dimethylhexa-1,5-dien-1-yl)oxy)hept-4-en-1-yl)-4-propylbenzene was isolated.

Computational Study of Tetrahedral Fullerenes Containing Fused Pentagon-Triples.

Fullerenes that violate the isolated pentagon rule are too reactive and were obtained only as endoor exohedral derivatives. Density functional theory using the B3LYP hybrid density functional was applied to investigate the electronic and structural properties of the ten smallest tetrahedral (Td or T point group) fullerenes containing four directly fused pentagon-triples. The influence of nitrogen doping and exohedral hydrogenation of the four reactive sites was also analyzed. Nucleus independent chemical shifts values computed using B3LYP/6-31G(d) are used as global and local aromaticity probe. The global strain energy is evaluated in terms of the pyramidalization (POAV) angle. The results show that the stability increases with the elimination of the energetically unfavorable strain.

Experimental and Theoretical Approach to Novel Polyfunctionalized Isoxazole

A novel, fast, and straightforward procedure for the synthesis of di- and trifunctionalized isoxazoles starting from 2-ethoxymethylenemalononitrile with different ratios of hydroxylamine in the presence of sodium acetate is described in this paper. The current method’s features include the availability of the starting materials, moderate reaction conditions, and the simplicity of the workup. The structures are characterized using different spectroscopic studies, such as infrared (IR), &lt;sup&gt;1&lt;/sup&gt;H/&lt;sup&gt;13&lt;/sup&gt;C nuclear magnetic resonance (NMR), and elemental analysis, in addition to X-ray single-crystal determination. The gauge-invariant atomic orbital (GIAO) &lt;sup&gt;1&lt;/sup&gt;H and &lt;sup&gt;13&lt;/sup&gt;C NMR chemical shift values of 5-aminoisoxazole-4-carbonitrile and 3,5-diaminoisoxazole-4-carboxamide are calculated in the ground state using the density functional theory (DFT) with the 6-311+G(d, p) basis set and are compared with the experimental data, in addition to the calculation of the molecular electrostatic potential (MEP) distribution, and the frontier molecular orbitals (FMOs) for the synthesized isoxazoles are illustrated theoretically.

Synthesis and structure of thiourea derivatives of functionally substituted pyridines

The article presents data on the synthesis and study of the structure of thiourea derivatives of functionally substituted pyridines. New thiourea derivatives containing a pharmacologically active pyridine moiety in their structure were obtained. As the starting synton, 2-amino-5-bromopyridine, 2-amino-3-hydroxypyridine and 2-aminomethylpyridine were selected. It was shown that the interaction of 2-amino-5-bromopyridine, 2-amino-3-hydroxypyridine and 2-aminomethylpyridine with ethyl and phenylisothiocyanates in ethanol leads to the formation of the corresponding pyridine-containing thioureas. The synthesis of the initial isothiocyanates was carriedout in situ from the corresponding acidic chlorides (benzoyl chloride and p-brombenzoyl chloride) by heating them with potassium thiocyanate in acetone. The structure of the synthe-sized compounds was studied by 1H and 13C NMR spectroscopy, as well as by the data of two-dimensional spectra of COSY (1H-1H) and HMQC (1H-13C). The values of chemical shifts, multiplicity, and integrated in-tensity of 1H and 13C signals in one-dimensional NMR spectra were determined. Using spectra in the formats COSY (1Н-1Н) and HMQC (1Н-13С), homo-and heteronuclear interactions were established, confirming the structure of the studied compounds.

A Volumetric Analysis of the 1H NMR Chemical Shielding in Supramolecular Systems.

The liquid state NMR chemical shift of protons is a parameter frequently used to characterize host–guest complexes. Its theoretical counterpart, that is, the 1H NMR chemical shielding affected by the solvent (1H CS), may provide important insights into spatial arrangements of supramolecular systems, and it can also be reliably obtained for challenging cases of an aggregation of aromatic and antiaromatic molecules in solution. This computational analysis is performed for the complex of coronene and an antiaromatic model compound in acetonitrile by employing the GIAO-B3LYP-PCM approach combined with a saturated basis set. Predicted 1H CS values are used to generate volumetric data, whose properties are thoroughly investigated. The 1H CS isosurface, corresponding to a value of the proton chemical shift taken from a previous experimental study, is described. The presence of the 1H CS isosurface should be taken into account in deriving structural information about supramolecular hosts and their encapsulation of small molecules.

Synthesis and radical copolymerization of 2‐(4‐((4‐isocyanophenyl)diazenyl)phenoxy)ethyl‐3‐phenylacrylate with maleic anhydride

AbstractA monomer containing a photochromic group was synthesized by condensation of 4‐(2‐hydroxyethyloxy)‐4‐cyanoazobenzene with cinnamoyl chloride. The structure and composition of the monomer were established by FTIR, UV–Vis, 1H NMR spectroscopy, and elemental analysis. The values of chemical shifts, multiplicity, and integrated intensity of 1H signals in one‐dimensional NMR spectra of the monomer were determined, and the homo‐ and heteronuclear interactions were found. The crystal structure of 4‐(2‐hydroxyethyloxy)‐4‐cyanoazobenzene was established using X‐ray diffraction analysis. A copolymer containing photochromic mesogenic fragment was synthesized by radical copolymerization of 2‐(4‐((4‐isocyanophenyl)diazenyl)phenoxy)ethyl‐3‐phenylacrylate with maleic anhydride.

Effect of aluminium incorporation on physicochemical properties and patent blue V photodegradation of magnesium phosphate materials

A series of magnesium phosphate samples modified by incorporation of aluminium, denoted MgAlP-x (where x indicates the Al molar ratio%; x = 0; 10; 20; 40%), have been prepared by coprecipitation method followed by characterization. Their structures have been investigated by using powder X-ray diffraction, the surface area by physisorption of nitrogen (BET), Fourier transform infrared (FTIR) were used to characterize the functional groups of solids and MAS–NMR spectroscopy. X-ray diffractograms for synthesized materials suggest the formation of mixed solids, such as Mg3(PO4)2, AlPO4 and Al2O3. Incorporation of aluminium into magnesium orthophosphate increased the temperature of crystallization, so that MgAlP-x systems retained amorphous up to 973 K. The specific surface area increases with aluminium content. 31P MAS–NMR spectra of calcined MgP shows a single peak at δ = +0.4 ppm and two overlapped signals for calcined MgAlP-x (x = 20 and 40%). But the dry solids present more than a single peak. The varying values of chemical shifts are due to the existence of different types of 31P structural configurations and oxygen environment. 27Al MAS-NMR spectra of sample exhibit two peaks, which were characteristic of the octahedral and tetrahedral environments of Al3+ ions. It was observed that the incorporation of Al in MgP material decreases the patent blue V (PB) photodegradation. The highest dye degradation was obtained over the MgP catalyst (without Al). No correlation between the adsorption before UV irradiation and the rate of photodegradation.

1,3,5-Triaza-7-Phosphaadamantane (PTA) as a 31P NMR Probe for Organometallic Transition Metal Complexes in Solution

Due to the rigid structure of 1,3,5-triaza-7-phosphaadamantane (PTA), its 31P chemical shift solely depends on non-covalent interactions in which the molecule is involved. The maximum range of change caused by the most common of these, hydrogen bonding, is only 6 ppm, because the active site is one of the PTA nitrogen atoms. In contrast, when the PTA phosphorus atom is coordinated to a metal, the range of change exceeds 100 ppm. This feature can be used to support or reject specific structural models of organometallic transition metal complexes in solution by comparing the experimental and Density Functional Theory (DFT) calculated values of this 31P chemical shift. This approach has been tested on a variety of the metals of groups 8–12 and molecular structures. General recommendations for appropriate basis sets are reported.

Synthesis and Characterization of Polyvanadium and Heteropoly-Tungsten Based Inorganic Wells Dawson Polyoxometalates Hybrids

The two new Wells-Dawson type polyoxometalatehybrids named as [(C4H9)4N]10H2[{C7H14O4C(CH2O)3P2V3W15O59] (D.Poms@Lig1), [(C4H9)4N)]5H2[C2H4OC(CH2O)3 P2V3W15O59] (D.Poms@Lig-2) have been synthesized with good percentage yields (65 and 75%, respectively). The newly prepared hybrids were characterized successfully by FT-IR, 1H, 13C, 31P, 51V NMR and UV-Visible spectroscopic methods. Parent Dawson polyoxometalates and ligands molecules display the strong metal-oxo (V–O) vibrational bands at 700 cm–1. After interaction, there is a little fluctuations in these vibrational bands and appeared at 757 and 750 cm–1 for V–O of D. Poms@Lig-1 and D.Poms@Lig-2, respectively. The strong peaks appeared at 824, 718 and 803, 754 cm–1 are assigned for ν(W–O–W) D.Poms@Lig-1 and D.Poms@Lig-2, respectively. In 1H NMR, the chemical shift value 2.95–2.94 ppm was observed C–CH2–O for D.Poms@Lig-1 and D.Poms@Lig-2, respectively. In 13C NMR, signal appears at 62.92 and 62.75 ppm are assigned for –CH2–C–CH2– for D.Poms@Lig-1, D.Poms@Lig-2, respectively. 51V NMR spectra showed peaks at –541.00 and –541.87 ppm for D.Poms@Lig-1 and D.Poms@Lig-2, respectively. 31P NMR spectra showed two peaks at δ = [–13.44, –7.19] ppm and [–13.44, –7.25] ppm for D.Poms@Lig-1, and D.Poms@Lig-1, respectively. The UV-Visible absorption spectra showed that there is just a little bit change in the intensity of the absorption bands among the absorption spectra of the ligands, hybrid compounds and parent Dawson POM.

Quantum Mechanical Study, Spectroscopic (FT-IR, FT-Raman and UV-Vis) Study, NBO, NLO Analysis and Molecular Docking Studies of 2-Ethoxy-4-(Pyridine-2yliminomethyl)-Phenol

Experimental and theoretical investigations on the molecular structure, electronic and vibrational characteristics of 2-ethoxy-4-(pyridine-2yliminomethyl)-phenol (2E4P2P) were presented. The vibrational frequencies were calculated by structure optimization based on DFT/B3LYP with 6-311++G(d,p) basis set. The simulated vibrational spectra of the molecule had shown good agreement with the observed spectra. The stability and charge delocalization of the title molecule were studied by natural bond orbital (NBO) analysis. The energy gap of the molecule was calculated with highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). The electronic transition was studied by UV-Vis analysis of the title molecule with same level of basis set. The non-linear optical (NLO) behavior, in terms of dipole moment, polarizability and first order hyperpolarizability, molecular electrostatic potential (MEP) and thermodynamic properties of the title compound were also calculated. Gauge independent atomic orbital (GIAO) method was used to calculate the 1H and 13C nuclear magnetic resonance (NMR) chemical shift values of 2E4P2P. Molecular docking studies were performed by Schrodinger software to establish the information about the interactions between the topoisomerase DNA gyrase enzymes and the novel compound.

Synthesis and structural elucidation of a series of isoflavones-based on FPR antagonists

Synthesis and structural elucidation of a series of isoflavones-based on FPR antagonists

Novel nonperipheral octa-3-hydroxypropylthio substituted metallo-phthalocyanines: synthesis, characterization, and investigation of their electrochemical, photochemical and computational properties.

The current study describes the synthesis, electrochemical, computational, and photochemical properties of octa (3-hydroxypropylthio) substituted cobalt (II) ( 4 ), copper (II) ( 5 ), nickel (II) ( 6 ) and zinc(II) ( 7 ) phthalocyanine derivatives. These novel compounds were characterized by elemental analysis,1H,13C NMR, FT-IR, UV-Vis, and MS. The redox behaviors of these metallo-phthalocyanines were investigated by the cyclic voltammetric method. The optimized molecular structure and gauge-including atomic orbital (GIAO)1H and13C NMR chemical shift values of these phthalocyanines in the ground state had been calculated by using B3LYP/6–31G(d,p) basis set. The outcomes of the optimized molecular structure were given and compared with the experimental NMR values. The photochemical properties including photodegradation and singlet oxygen generation of zinc(II) phthalocyanine were studied in DMSO solution for the determination of its photosensitizer behaviors.