Nuclear Resonance Effect Research Articles

Structure of a new usnic acid derivative from a deacylating Mannich reaction: NMR studies supported by theoretical calculations of chemical shifts.

In a conventional Mannich reaction using piperidine, hydroxypiperidines, morpholine, and N-methylpiperazine with usnic acid, a deacetylation was observed resulting in a substitution at C-2, a loss of an acetyl group, and a Mannich base with a stabilized enol. The enol has a hydrogen bond to the nitrogen of the secondary amine. The structure was investigated by nuclear magnetic resonance and deuterium isotope effects on 13 C chemical shifts as well as with density functional theory calculations to study the changed hydrogen bond pattern. It was found that the hydrogen bond involving the OH-9 group in chloroform forms a strong hydrogen bond than in usnic acid itself and that this hydrogen bond becomes even stronger in the more polar solvent, dimethylsulfoxide. Tautomerism was observed in the Mannich base as demonstrated by deuterium isotope effects on chemical shifts. The position of the tautomeric equilibrium depends on the solvent, and the position of the equilibrium governs the strength of the OH-9…O═C hydrogen bond.

History of NMR Gyroscope Development in Russia in 1960–2000s

This paper is dedicated to the history of development of a gyroscope based on the nuclear magnetic resonance (NMR) effect, in the USSR and Russia. The paper presents early references to the idea of using the electrons and other elementary particles, as well as atoms as a working substance in gyroscopy. The main stages of development of a NMR-gyroscope construction principles are briefly described. Works on spin oscillators and stabilizers based on mercury isotopes and on exchange-oriented nuclei of noble gases are discussed. The paper shows how these stages are linked with emerging new areas (disciplines) of applied nuclear physics, such as spectroscopy (electronic paramagnetic resonance and NMR), optical pumping, and exchange orientation.

π-Conjugated Polymers Incorporating a Novel Planar Quinoid Building Block with Extended Delocalization and High Charge Carrier Mobility.

Two novel conjugated polymers incorporating quinoidal thiophene are successfully synthesized. By combining 1D nuclear magnetic resonance (NMR) and 2D nuclear Overhauser effect spectroscopy analyses, the isomeric form of the major quinoid monomer is clearly identified as the asymmetric Z, E-configuration. The quinoidal polymers are synthesized via Stille polymerization with thiophene or bithiophene. Both quinoidal polymers exhibit the low band gap of 1.45 eV and amphoteric redox behavior, indicating extended conjugation owing to the quinoidal backbone. These quinoidal polymers show ambipolar behaviors with high charge carrier mobilities when applied in organic field-effect transistors. In addition, the radial alignment of polymer chains achieved by off-center spin-coating leads to further improvement of device performance, with poly(quinoidal thiophene-bithiophene) exhibiting a high hole mobility of 8.09 cm2 V-1 s-1 , which is the highest value among the quinoidal polymers up to now. Microstructural alteration via thermal annealing or off-center spin-coating is found to beneficially affect charge transport. The enhancement of crystallinity with strong π-π interactions and the nanofibrillar structure arising from planar well-delocalized quinoid units is considered to be responsible for the high charge carrier mobility.

Powerful Sources for High Frequency Electromagnetic Transducers for Measurement, Monitoring and Diagnostics

Conceptual provisions for the construction of miniaturized variable parameter of high-power high-frequency broadband radio pulse amplifiers have been developed: filling frequency, duration, significant peak current and peak voltage. A circuit-based solution is proposed for constructing high-frequency radio signal of high-power amplifiers, whose frequency varies in the interval 0.1 … 20 MHz, the time duration is 1 … 10 periods of pulse filling frequency, with an output current that reaches 200 A and voltage up to 4 kV. The use of the developed powerful amplifier will allow creating and improving the instruments for ultrasonic quality control of products by electromagnetic-acoustic transducers in industry and electromagnetic transducers in medical devices using the effect of nuclear magnetic resonance, electron paramagnetic resonance, and also in measuring devices.

Identification and Characterization of 3-epi-Rotundone, a Novel Stereoisomer of Rotundone, in Several Kinds of Fruits.

A novel stereoisomer of rotundone, 3-epi-rotundone, was identified in the aroma of grapefruit, orange, apple, and mango. 3-epi-Rotundone was prepared by the isomerization of rotundone, and its structural elucidation was confirmed by comparing the 1D and 2D nuclear magnetic resonance and nuclear Overhauser effect spectroscopy spectra with those of rotundone. The odor thresholds of rotundone and 3-epi-rotundone in water were determined by a triangle test as 5 and 19100 ng/kg, respectively. The odor of 3-epi-rotundone was evaluated as woody, spicy, peppery, citrus, grapefruit-like, powdery, and celery-like, which was a greater range of odor characteristics than that for rotundone. Results of odor evaluation of 3-epi-rotundone revealed that its unique organoleptic properties, which were odor description (woody, spicy, and peppery), anosmic properties in neat form, and strong adaptation, were similar to those of rotundone. 3-epi-Rotundone might be a valuable substance to apply new types of woody, peppery, and spicy notes.

Chirality-sensitive nuclear magnetic resonance effects induced by indirect spin-spin coupling.

It is predicted that, for two spin-1/2 nuclei coupled by indirect spin-spin coupling in a chiral molecule, chirality-sensitive induced electric polarization can be observed at the frequencies equal to the sum and difference between the spin resonance frequencies. Also, an electric field oscillating at the difference frequency can induce spin coherences which allow the direct discrimination between enantiomers by nuclear magnetic resonance. The dominant contribution to the magnitude of these expected chiral effects is proportional to the permanent electric dipole moment and to the antisymmetric part of the indirect spin-spin coupling tensor of the chiral molecule. Promising compounds for experimental tests of the predictions are derivatives of 1,3-difluorocyclopropene.

Inclusion complex of erlotinib with sulfobutyl ether-β-cyclodextrin: Preparation, characterization, in silico, in vitro and in vivo evaluation

The aim of the study was to investigate the impact of erlotinib sulfobutyl ether beta-cyclodextrin complex (ERL-SBE-β-CD) on ERL dissolution rate and oral bioavailability. Preliminary comparative phase solubility study indicated ERL exhibited maximum solubility in SBE-β-CD solution. Optimal experimental design confirmed freeze drying of SBE-β-CD:ERL in 1:1.05 molar ratio as the optimum method. Differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), proton nuclear magnetic resonance (1H NMR) and two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY NMR) confirmed the inclusion complexation. The in silico computational study, employed to analyze the comparative interactions of ERL with SBE-β-CD and β-CD, indicated ease of ERL-SBE-β-CD complexation. In vitro dissolution and in vivo bioavailability studies further confirmed the ERL-SBE-β-CD as a valuable approach to enhance ERL oral bioavailability with 3.6-fold increase in relative oral bioavailability with higher Cmax (134.29±36.51 vs. 42.36±1.75μg/ml) and AUC0–∞ (2103.47±156.75 vs.580.43±71.91μg/mlh) over the free drug. The complex exhibited 3.2-fold increase in Cmax with 5.4-fold decrease in Tmax (0.5±0.2 vs. 2.7±0.8h) in comparison to pure ERL. Thus, ERL-SBE-β-CD complexation exhibits a potential to enhance oral bioavailability of ERL leading to reduce dose and dose-related side effects.

A theoretical study of potentially observable chirality-sensitive NMR effects in molecules.

Two recently predicted nuclear magnetic resonance effects, the chirality-induced rotating electric polarization and the oscillating magnetization, are examined for several experimentally available chiral molecules. We discuss in detail the requirements for experimental detection of chirality-sensitive NMR effects of the studied molecules. These requirements are related to two parameters: the shielding polarizability and the antisymmetric part of the nuclear magnetic shielding tensor. The dominant second contribution has been computed for small molecules at the coupled cluster and density functional theory levels. It was found that DFT calculations using the KT2 functional and the aug-cc-pCVTZ basis set adequately reproduce the CCSD(T) values obtained with the same basis set. The largest values of parameters, thus most promising from the experimental point of view, were obtained for the fluorine nuclei in 1,3-difluorocyclopropene and 1,3-diphenyl-2-fluoro-3-trifluoromethylcyclopropene.

The role of encapsulation by β-cyclodextrin in the interaction of raloxifene with macromolecular targets: a study by spectroscopy and molecular modeling.

We report the binding of the drug raloxifene with Calf thymus DNA (ctDNA) and bovine serum albumin (BSA) in the presence and absence of β-cyclodextrin (β-CD) and explain the influence of β-cyclodextrin on the binding of the drug to macromolecules. UV-Vis absorption, fluorescence, proton nuclear magnetic resonance and two-dimensional rotating-frame nuclear overhauser effect spectroscopic techniques are used to study the stoichiometry and the binding strength of the complexes. Molecular modeling is used in combination with other techniques to propose the structure of the inclusion complex and the interaction with ctDNA. The Stern-Volmer quenching constants of the interaction of raloxifene with ctDNA in aqueous and in β-CD solution are compared. The competition for binding of ctDNA with raloxifene and Methylene Blue is studied. The apparent binding constant and the number of binding sites for the binding of raloxifene with BSA in aqueous solution are significantly different from those in the presence of β-CD. The influence of β-CD on the binding of the small molecules with biological macromolecules is discussed. We infer that the binding strengths between raloxifene and macromolecules, viz., ctDNA and BSA are influenced by the β-CD encapsulation. These results may suggest new ways to tune the drug binding to biomacromolecules by encapsulating specific moieties of drugs.

Magnetic Nanoparticles and microNMR for Diagnostic Applications

Sensitive and quantitative measurements of clinically relevant protein biomarkers, pathogens and cells in biological samples would be invaluable for disease diagnosis, monitoring of malignancy, and for evaluating therapy efficacy. Biosensing strategies using magnetic nanoparticles (MNPs) have recently received considerable attention, since they offer unique advantages over traditional detection methods. Specifically, because biological samples have negligible magnetic background, MNPs can be used to obtain highly sensitive measurements in minimally processed samples. This review focuses on the use of MNPs for in vitro detection of cellular biomarkers based on nuclear magnetic resonance (NMR) effects. This detection platform, termed diagnostic magnetic resonance (DMR), exploits MNPs as proximity sensors to modulate the spin-spin relaxation time of water molecules surrounding the molecularly-targeted nanoparticles. With new developments such as more effective MNP biosensors, advanced conjugational strategies, and highly sensitive miniaturized NMR systems, the DMR detection capabilities have been considerably improved. These developments have also enabled parallel and rapid measurements from small sample volumes and on a wide range of targets, including whole cells, proteins, DNA/mRNA, metabolites, drugs, viruses and bacteria. The DMR platform thus makes a robust and easy-to-use sensor system with broad applications in biomedicine, as well as clinical utility in point-of-care settings.

Synthesis and Dynamic NMR Study of a Functionalized Sulfonamide Phosphonate Diester

Protonation of the highly reactive 1:1 intermediate produced in the reaction between triphenylphosphite and activated acetylene by sulfonamide leads to a phosphonate ylide, which undergoes methanol elimination in the presence of moisture to produce a highly functionalized sulfonamide phosphonate diester. A dynamic nuclear magnetic resonance (NMR) effect is observed in the 1H NMR spectra of this compound as a result of restricted rotation around the single C‒N bond. The coalescence temperature was observed at TC = 352.5 K, and the free energy of activation (ΔG#) for this process is 75.6 ± 2 kJ.mol−1. GRAPHICAL ABSTRACT

Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity

BackgroundPolyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug.MethodsThe dendrimer-phenylbutazone complexes were characterized by 1H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated.ResultsAqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines.ConclusionAlthough the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development.

Effects of low-energy NMR on posttraumatic osteoarthritis: observations in a rabbit model

To evaluate a possible beneficial effect of low-energy nuclear magnetic resonance (NMR) on cartilage in moderate and severe posttraumatic osteoarthrosis in the rabbit using a macroscopic and a histological grading system. Following transection of the anterior cruciate ligament of both knees in 24 skeletally mature New Zealand White rabbits, we observed different stages of osteoarthrosis (OA) 6 and 12 weeks postoperatively. Animals were randomized into four groups: Group 1 (eight animals) was treated after 6 weeks by NMR (magnetic field: 20-40 G, interference field: 2.35 mT, 100 kHz; MBST Device, MedTec, Germany), with 1 h of treatment for seven consecutive days. Group 2 was treated in the same pattern after 12 weeks. The sham-operated groups 3 and 4 received no treatment. Seven days after the last treatment, OA was macroscopically graded and hyaline cartilage of the load bearing area was evaluated histologically according to the Mankin scale. Macroscopically, there was less OA in group 1 (p < 0.01), but did not reveal significance in group 2 (p = 0.11) compared to the sham groups. There was no significant difference in the Mankin score in both of the treated groups compared to the control groups (group 1: p = 0.36; group 2: p = 0.81). The results showed some beneficial macroscopic effect in mild OA with less macroscopic OA signs in the treated animals but without a histological effect in the Mankin scale. There was no effect found in the pattern later OA. On behalf of these results, NMR for the treatment of posttraumatic OA cannot be recommended at this point of time.

Spin Temperature Model for Distant Electron Nuclear Double Resonance Effect

To clarify the mechanism of the distant electron nuclear double resonance effect, ruby Al2O3 (Cr3+) was studied by ENDOR technique in the V-band (50 GHz band). The most prominent ENDOR effect was observed at fields a little off the resonance field of electron spin resonance (ESR). To interpret this phenomenon, we propose the spin temperature model which deals with thermal equilibrium between the electron spin system and the nuclear spin system on the frame rotating at the Larmor frequency of the electron. Below the resonance field, the ENDOR effect caused by the energy flow from the nuclear spin system to the electron spin system is most prominent when the electron spin temperature is the lowest compared with the nuclear spin temperature. In the higher magnetic field than the resonance field where the electron spin temperature is negative, the ENDOR effect is caused by the electron spin deexcitation induced by the fluctuations of the effective field.

Anomalous enantioselectivity in the sharpless asymmetric dihydroxylation reaction of 24-nor-5beta-cholest-23-ene-3alpha,7alpha,12alpha-triol: synthesis of substrates for studies of cholesterol side-chain oxidation.

Recently we described a block in bile acid synthesis in cerebrotendinous xanthomatosis (CTX), a lipid storage disease related to an inborn error of bile acid metabolism. In this disease a defect in hepatic microsomal (24S) hydroxylation blocks the transformation of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol into (24S) 5beta-cholestane-3alpha,7alpha,12alpha,24,25- pentol and cholic acid. Mitochondrial cholesterol 27-hydroxylation has also been reported to be abnormal in CTX subjects, but the relative importance of the enzymatic defect in this alternative microsomal pathway (namely, the 24S hydroxylation of 5beta-cholestane-3alpha,7alpha, 12alpha,25-tetrol relative to the abnormality in mitochondrial 27-hydroxylase) has not been established in CTX. To delineate the sequence of side-chain hydroxylations and the enzymatic block in bile acid synthesis, we synthesized the (23R and 23S) 24-nor-5beta-cholestane-3alpha,7alpha, 12alpha,23,25-pentols utilizing a modified Sharpless asymmetric dihydroxylation reaction on 24-nor-5beta-cholest-23-ene-3alpha, 7alpha, 12alpha-triol, a C26 analog of the naturally occurring C27 bile alcohol, 5beta-cholest-24-ene-3alpha,7alpha,12alpha-triol . Stereospecific conversion of the unsaturated 24-nor triol to the corresponding chiral compounds (23R and 23S), 24-nor-5beta-cholestane-3alpha,7alpha,12alpha,23 ,25-pentols, was quantitative. However, conversion of the unsaturated 24-nor triol to the chiral nor-pentols had absolute stereochemistry opposite to the products predicted by the Sharpless steric model. The absolute configurations and enantiomeric excess of the C26 nor-pentols and the C27 pentols (synthesized from 5beta-cholest-24-ene-3alpha,7alpha,12alpha-triol for comparison) were confirmed by nuclear magnetic resonance and lanthanide-induced circular dichroism Cotton effect measurements. These results may contribute to a better understanding of the role of the 24S-hydroxylation vs. 27-hydroxylation step in cholic acid biosynthesis.

Rigid-rod aramids incorporating polymethylated monomers

The design and synthesis of a series of aromatic polyamides incorporating amino-, aminobenzoyl- and aminophenoxy-derivatives of durene (1,2,4,5-tetramethylbenzene) is described. A number of these polyaramids exhibited good solubility in polar organic solvents. Solutions of these polyaramids were amorphous exhibiting no lyotropic liquid crystalline behaviour. Proton nuclear magnetic resonance (NMR), carbon-13 NMR, and nuclear overhauser effect spectroscopy (NOESY) were used to investigate the structure of these polymers. The physical properties of these polyaramids were determined by differential scanning calorimetry (DSC), thermogravimetry (TG) and X-ray diffraction (XRD).

The effect of Gd substitution on the magnetic properties and hyperfine fields of melt-spun Nd4Fe77.5B18.5 alloys

The hyperfine fields (HFS) and magnetic properties of amorphous and crystallized GdxNd4-xFe77.5B18.5 (0<or=x<or=4) alloys have been investigated by means of magnetization measurements, zero-field spin-echo nuclear magnetic resonance (NMR) and Mossbauer effect (ME). For comparison, the x-ray diffraction (XRD) pattern of Nd4Fe77.5B18.5 annealed at 670 degrees C for a short time is also presented. It is found that the Curie temperatures of amorphous alloys increase slightly on addition of Gd, but the coercive fields of crystallized alloys decrease monotonically with increasing x. NMR, ME and XRD indicate that these samples consist of Fe3B with a body-centred tetragonal structure (BCT Fe3B) and a small amount of alpha -Fe, with no Nd2Fe14B and Nd1.1Fe4B4 phases. Furthermore, the NMR results indicate that the 11B HFS of BCT Fe3B increase linearly from 25.3 kOe (34.7 MHz) for x=0 to 26.3 kOe (36.0 MHz) for x=4, but that of alpha -Fe does not change with increasing Gd concentration; the Mossbauer spectra (MSs) show that the relative intensity of the subspectrum corresponding to 57Fe at FeIII(8g) sites in BCT Fe3B is about 5% weaker than those of the other two, implying that about 5 at.% Fe atoms in this site are substituted by other atoms. According to this, it may be reasonable to assume that the R atoms enter into the BCT Fe3B.

Magnetism and hyperfine fields in YFe10V2: a combined nuclear magnetic resonance and Mossbauer study

A combined nuclear magnetic resonance (NMR) and Mossbauer effect study of YFe10V2 has been carried out. Based on the 57Fe hyperfine fields (HFS) obtained from the Mossbauer results, the resonance lines of the NMR spectrum are assigned and the site preference of V atoms is determined. On the other hand, according to the site preference of vanadium atoms determined by NMR, together with neutron diffraction results, the 57Fe Mossbauer spectrum is fitted. It can be deduced from the NMR results that the existence of one nearest-neighbour Fe atom leads to an increase in the V HF of about 0.35, and the core electron polarization contribution Hcp, the 4s conduction electron polarization contribution Hs and the effect of the second-nearest-neighbour Fe atoms on the HF sites cannot be negligible.

Nuclear resonance effects in the analysis of proton backscattering from carbon and silicon films

The use of elastic resonance backscattering of protons in the analysis of thin films is sometimes an advantage. It allows precise and accurate thickness determination even when the energy calibration of the system is marginal. The availability of reliable values for the scattering cross section in the region of the resonance is essential. We have remeasured the elastic scattering cross section of protons on C and Si in the energy region between 450 and 2200 keV at a laboratory angle of 155°. Our data are compared with earlier measurements. The usefulness of the incorporation of resonance scattering in the spectrum analysis is demonstrated.

Effect of the nuclear d-t resonance on muon sticking in micro-catalyzed fusion.

Beginning with a previously developed theory of the fusion reaction in the dt${\mathrm{\ensuremath{\mu}}}^{\mathrm{\ensuremath{-}}}$ system [Belyaev, R\'evai, and Zubarev, Phys. Lett. B 219, 157 (1989)] we have derived a calculation scheme of the muon-sticking probability in \ensuremath{\mu}-catalyzed fusion that generalizes the commonly adopted sudden approximation. We have found a large nuclear resonance effect on the sticking coefficient. Our calculations disagree with the values extracted from the experiments by Breunlich et al. [Phys. Rev. Lett. 58, 329 (1987)] while they seem to confirm those of Jones et al. [Phys. Rev. Lett. 58, 1407 (1987)].