Descripción: Preparation of chiral heterocyclic compounds of the thiadiazoline types, starting from natural α,β-unsaturated and bicyclic terpenones is described. Stereochemical assignment of the compounds synthesized was performed by NMR spectroscopy and X-ray analysis. ©ARKAT.

Descripción: We have described a method for preparation of [10B]-enriched-8- dihydroxyborylharmine (III) and characterized it by their spectral properties (MS, IR and NMR). This compound is a potential BNCT agent.

Descripción: New organophosphorus insecticides of dialkylsulphoximines derived with activity upon acetylcholinesterase were synthesized. The obtained compounds were characterized by NMR and IR, and anticholinesterase activity and toxicity was measured. A simulation through computer was done in order to establish the relationship between structure and activity.

Descripción: In the present work a set of formal relations connecting different approaches to calculate relativistic effects on magnetic molecular properties are proven. The linear response (LR) within the elimination of the small component (ESC), Breit Pauli, and minimal-coupling approaches are compared. To this end, the leading order ESC reduction of operators within the minimal-coupling four-component approach is carried out. The equivalence of all three approaches within the ESC approximation is proven. It is numerically verified for the NMR nuclear-magnetic shielding tensor taking HX and C H3 X (X=Br,I) as model compounds. Formal relations proving the gauge origin invariance of the full relativistic effect on the NMR nuclear-magnetic shielding tensor within the LR-ESC approach are presented. © 2006 American Institute of Physics.

Descripción: The phytochemical study of two species of Jaborosa caulescens (var. caulescens and var. bipinnatifida) yielded the four new withanolides 1-4. The structures of the new compounds were determined using a combination of spectroscopic techniques (including 1D and 2D NMR) and Molecular Modeling.

Descripción: A new trechonolide-type withanolide, jaborosolactol, possessing a hemiketal ring system and a 5-membered lactol, has been isolated from the aerial parts of Jaborosa lanigera. The structure was elucidated based on spectroscopic and spectrometric methods (ID and 2D NMR, MS). The feeding deterrent activity of the compound against the Mediterranean fruit fly Ceratitis capitata was examined. © 2007 Verlag der Zeitschrift für Naturforschung.

Descripción: We investigate the importance of relativistic effects on NMR shielding constants and chemical shifts of linear HgL2 (L = Cl, Br, I, CH 3) compounds using three different relativistic methods: the fully relativistic four-component approach and the two-component approximations, linear response elimination of small component (LR-ESC) and zeroth-order regular approximation (ZORA). LR-ESC reproduces successfully the four-component results for the C shielding constant in Hg(CH3)2 within 6 ppm, but fails to reproduce the Hg shielding constants and chemical shifts. The latter is mainly due to an underestimation of the change in spin-orbit contribution. Even though ZORA underestimates the absolute Hg NMR shielding constants by ∼2100 ppm, the differences between Hg chemical shift values obtained using ZORA and the four-component approach without spin-density contribution to the exchange-correlation (XC) kernel are less than 60 ppm for all compounds using three different functionals, BP86, B3LYP, and PBE0. However, larger deviations (up to 366 ppm) occur for Hg chemical shifts in HgBr 2 and HgI2 when ZORA results are compared with four-component calculations with non-collinear spin-density contribution to the XC kernel. For the ZORA calculations it is necessary to use large basis sets (QZ4P) and the TZ2P basis set may give errors of ∼500 ppm for the Hg chemical shifts, despite deceivingly good agreement with experimental data. A Gaussian nucleus model for the Coulomb potential reduces the Hg shielding constants by ∼100-500 ppm and the Hg chemical shifts by 1-143 ppm compared to the point nucleus model depending on the atomic number Z of the coordinating atom and the level of theory. The effect on the shielding constants of the lighter nuclei (C, Cl, Br, I) is, however, negligible. © 2011 American Institute of Physics.

Descripción: The crude polysaccharide from cystocarpic Callophyllis variegata was fractionated with potassium chloride yielding three minor fractions which precipitated between 0.05-0.10 M KCl, 1.20-1.25 M KCl and 1.80-2.00 M KCl, and a main product soluble in 2.00 M KCl. These fractions were analysed and structural analysis of the major one was carried out by methylation, FT-IR and 13C NMR.

Descripción: The use of neutron inelastic scattering measurements to determine the nature of the solid-state transitions in globular compounds is proposed and exemplified. Patterns were taken of the high- and low-temperature phases of solid cyclohexane, 2-2-dimethylbutane, and 1-4-diazo-bicyclo-(2.2.2)-octane. The first two have broad inelastic scattering peaks in the low-temperature phase. In the high-temperature phase these peaks disappear and the elastic peak broadens markedly. These changes are attributed to "quasi-free- rotation" of the molecules. Inelastic peaks do not appear in 1-4-diazo-bicyclo-(2.2.2)-octane, and the elastic peak does not broaden appreciably in the high-temperature phase. Self-diffusion coefficients D 3=4.5×10-5 cm2/sec for cyclohexane and D3=8.6×10-5 cm2/sec for 2-2-dimethylbutane were determined from the patterns of the liquids at 300°K using the "small motions" approximation. These values are larger than those obtained from NMR measurements, presumably as a result of irreversible rotation of the molecules.

Descripción: Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate the calcium/calmodulin signaling pathway either by changing intracellular Ca2+ concentration via activation of its G-protein-coupled membrane receptors, or through a direct interaction with calmodulin (CaM). The present work studies the direct interaction of melatonin with intact calcium-saturated CaM both experimentally, by fluorescence and nuclear magnetic resonance spectroscopies, and theoretically, by molecular dynamics simulations. The analysis of the experimental data shows that the interaction is calcium-dependent. The affinity, as obtained from monitoring 15N and 1H chemical shift changes for a melatonin titration, is weak (in the millimolar range) and comparable for the N- and C-terminal domains. Partial replacement of diamagnetic Ca2+ by paramagnetic Tb3+ allowed the measurement of interdomain NMR pseudocontact shifts and residual dipolar couplings, indicating that each domain movement in the complex is not correlated with the other one. Molecular dynamics simulations allow us to follow the dynamics of melatonin in the binding pocket of CaM. Overall, this study provides an example of how a combination of experimental and theoretical approaches can shed light on a weakly interacting system of biological and pharmacological significance.

Descripción: The aggregation of α-synuclein is characteristic of Parkinson's disease (PD) and other neurodegenerative synucleinopathies. The 140-aa protein is natively unstructured; thus, ligands binding to the monomeric form are of therapeutic interest. Biogenic polyamines promote the aggregation of α-synuclein and may constitute endogenous agents modulating the pathogenesis of PD. We characterized the complexes of natural and synthetic polyamines with α-synuclein by NMR and assigned the binding site to C-terminal residues 109-140. Dissociation constants were derived from chemical shift perturbations. Greater polyamine charge (+ 2 → + 5) correlated with increased affinity and enhancement of fibrillation, for which we propose a simple kinetic mechanism involving a dimeric nucleation center. According to the analysis, polyamines increase the extent of nucleation by ∼104 and the rate of monomer addition ∼40-fold. Significant secondary structure is not induced in monomeric α-synuclein by polyamines at 15°C. Instead, NMR reveals changes in a region (aa 22-93) far removed from the polyamine binding site and presumed to adopt the β-sheet conformation characteristic of fibrillar α-synuclein. We conclude that the C-terminal domain acts as a regulator of α-synuclein aggregation.

Descripción: In order to increase the understanding of the interactions which define the planar conformation of the methoxy group with respect to the aryl ring in methyl aryl ethers and the effect these interactions have on the methoxy NMR parameters, 17O and 13C spectra were measured and ab initio optimized geometries were calculated for three different conformations of the methoxy group in 2-methoxy-5-X-pyridines (X = H, NO2, and NH2). 17O and 13C chemical shifts were also calculated using the LORG approach. It was found that, contrary to what has been commonly assumed, the oxygen and the carbon of the methoxy group are deshielded when the electronic resonance interaction is increased. Therefore, the large 13C deshielding effect observed for a conformation with an out-of-plane methoxy group in aryl methyl ethers and related compounds has to be attributed to the inhibition of the attractive van der Waals forces between the methyl moiety and the aromatic ortho-cis carbon atom. © 1993 American Chemical Society.

Descripción: We have employed the Douglas-Kroll-Hess approximation to derive the perturbative Hamiltonians involved in the calculation of NMR spin-spin couplings in molecules containing heavy elements. We have applied this two-component quasirelativistic approach using finite perturbation theory in combination with a generalized Kohn-Sham code that includes the spin-orbit interaction self-consistently and works with Hartree-Fock and both pure and hybrid density functionals. We present numerical results for one-bond spin-spin couplings in the series of tetrahydrides C H4, Si H4, Ge H4, and Sn H4. Our two-component Hartree-Fock results are in good agreement with four-component Dirac-Hartree-Fock calculations, although a density-functional treatment better reproduces the available experimental data. © 2005 American Institute of Physics.

Descripción: The phytochemical investigation of the dichloromethane-soluble part of the methanol extract obtained from the fruits of Melia azedarach afforded one new tirucallanetype triterpene, 3-α-tigloylmelianol (1) and three known tirucallanes, melianone (2), 21-β-acetoxy-melianone (3), and methyl kulonate (4). The structure of the isolated compounds was mainly determined by 1D and 2D NMR experiments as well as HPLC-Q-TOF mass spectrometry. The cytotoxicity of the isolated compounds toward the human lung adenocarcinoma epithelial cell line A549 was determined, while no activity was observed against the phytonematode Meloidogyne incognita. © 2010 by the authors.

Descripción: A procedure, based on a continuous transformation of the origin of the (quantum mechanical) current density that sets the diamagnetic contribution to zero (CTOCD-DZ) all over the molecular domain, is applied to determine shielding polarizabilities to first order in a perturbing electric field. In any calculations relying on the algebraic approximation, irrespective of size and quality of the (gaugeless) basis set employed, all the components of the CTOCD-DZ magnetic shielding polarizability are origin independent, and the constraints for charge and current conservation are exactly satisfied. The effects of a static uniform electric field on the nuclear magnetic resonance (NMR) shielding of H2O2, F2, H2C2, H2CO, NH3, HCN, and HNC molecules have been investigated within the CTOCD-DZ method, and compared with the conventional results evaluated via the same basis sets, and with theoretical results taken from the literature. © 2000 American Institute of Physics.

Descripción: Preparation of chiral heterocyclic compounds of the thiadiazoline types, starting from natural terpenones such as fenchone, camphor and menthone, is described. Stereochemical assignment of the compounds synthesized was performed by NMR spectroscopy and X-ray analysis.

Descripción: In the present work, numerical results of the nuclear spin-rotation (SR) tensor in the series of compounds HX (X=H,F,Cl,Br,I) within relativistic 4-component expressions obtained by Aucar [J. Chem. Phys. 136, 204119 (2012)10.1063/1.4721627] are presented. The SR tensors of both the H and X nuclei are discussed. Calculations were carried out within the relativistic Linear Response formalism at the Random Phase Approximation with the DIRAC program. For the halogen nucleus X, correlation effects on the non-relativistic values are shown to be of similar magnitude and opposite sign to relativistic effects. For the light H nucleus, by means of the linear response within the elimination of the small component approach it is shown that the whole relativistic effect is given by the spin-orbit operator combined with the Fermi contact operator. Comparison of "best estimate" calculated values with experimental results yield differences smaller than 2-3 in all cases. The validity of "Flygares relation" linking the SR tensor and the NMR nuclear magnetic shielding tensor in the present series of compounds is analyzed. © 2013 American Institute of Physics.

Descripción: Frataxin (FXN) is an α/β protein that plays an essential role in iron homeostasis. Apparently, the function of human FXN (hFXN) depends on the cooperative formation of crucial interactions between helix α1, helix α2, and the C-terminal region (CTR) of the protein. In this work we quantitatively explore these relationships using a purified recombinant fragment hFXN90-195. This variant shows the hydrodynamic behavior expected for a monomeric globular domain. Circular dichroism, fluorescence, and NMR spectroscopies show that hFXN90-195 presents native-like secondary and tertiary structure. However, chemical and temperature induced denaturation show that CTR truncation significantly destabilizes the overall hFXN fold. Accordingly, limited proteolysis experiments suggest that the native-state dynamics of hFXN90-195 and hFXN90-210 are indeed different, being the former form much more sensitive to the protease at specific sites. The overall folding dynamics of hFXN fold was further explored with structure-based protein folding simulations. These suggest that the native ensemble of hFXN can be decomposed in at least two substates, one with consolidation of the CTR and the other without consolidation of the CTR. Explicit-solvent all atom simulations identify some of the proteolytic target sites as flexible regions of the protein. We propose that the local unfolding of CTR may be a critical step for the global unfolding of hFXN, and that modulation of the CTR interactions may strongly affect hFXN physiological function. © 2012 Roman et al.

Descripción: We have studied the biochemical features, the conformational preferences in solution, and the DNA binding properties of human p8 (hp8), a nucleoprotein whose expression is affected during acute pancreatitis. Biochemical studies show that hp8 has properties of the high mobility group proteins, HMG-I/Y. Structural studies have been carried out by using circular dichroism (near- and far-ultraviolet), Fourier transform infrared, and NMR spectroscopies. All the biophysical probes indicate that hp8 is monomeric (up to 1 mM concentration) and partially unfolded in solution. The protein seems to bind DNA weakly, as shown by electrophoretic gel shift studies. On the other hand, hp8 is a substrate for protein kinase A (PKA). The phosphorylated hp8 (PKAhp8) has a higher content of secondary structure than the nonphosphorylated protein, as concluded by Fourier transform infrared studies. PKAhp8 binds DNA strongly, as shown by the changes in circular dichroism spectra, and gel shift analysis. Thus, although there is not a high sequence homology with HMG-I/Y proteins, hp8 can be considered as a HMG-I/Y-like protein.