Proton Nuclear Magnetic Resonance Signals Research Articles

Quaternary ammonium chitosan-based active packaging films incorporated with dialdehyde guar gum-proanthocyanidins conjugates: Characterization and application in the edible coating of pork

In this study, antioxidant and antibacterial proanthocyanidins (PA) were covalently conjugated with dialdehyde guar gum (DGG) to produce DGG-PA conjugates. Then DGG-PA conjugates were incorporated into quaternary ammonium chitosan (QAC)-based matrix to create QAC/DGG-PA films. The structure, physicochemical properties, and antioxidant and antibacterial effects of DGG-PA conjugates and QAC/DGG-PA films were analyzed. The active packaging potentials of QAC/DGG-PA film-forming solutions in the edible coating of pork loins were evaluated. Results showed DGG-PA conjugates had unique UV absorption peak (280 nm), infrared bands (1610 and 1521 cm−1) and proton nuclear magnetic resonance signals (6.82 ppm) of PA groups. DGG-PA conjugates showed amorphous state with sheet-like and fibrous morphology. DGG-PA conjugates had good biocompatibility and antioxidant and antibacterial effects. After adding DGG-PA conjugates, the surface of QAC-based films became smooth and the crystallographic nature of the films declined. DGG-PA conjugates elevated the light/water vapor/oxygen barrier performances, mechanical properties, and antioxidant and antibacterial effects of QAC-based films. QAC/DGG-PA edible coatings effectively prolonged the shelf life of pork loins from 4 days to 6−10 days. Results verified QAC/DGG-PA films and their film-forming solutions had good application potentials in active packaging.

The Landscape of Gold Nanocrystal Surface Chemistry.

ConspectusGold nanoparticles (AuNPs) exhibit unique size- and shape-dependent properties not obtainable at the macroscale. Gold nanorods (AuNRs), with their morphology-dependent optical properties, ability to convert light to heat, and high surface-to-volume ratios, are of great interest for biosensing, medicine, and catalysis. While the gold core provides many fascinating properties, this Account focuses on AuNP soft surface coatings, which govern the interactions of nanoparticles with the local environments. Postmodification of AuNP surface chemistry can greatly alter NP colloidal stability, nano-bio interactions, and functionality. Polyelectrolyte coatings provide controllable surface-coating thickness and charge, which impact the composition of the acquired corona in biological settings. Covalent modification, in which covalently bound ligands replace the original capping layer, is often performed with thiols and disulfides due to their ability to replace native coatings. N-heterocyclic carbenes and looped peptides expand the possible functionalities of the ligand layer.The characterization of surface ligands bound to AuNPs, in terms of ligand density and dynamics, remains a challenge. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for understanding molecular structures and dynamics. Our recent NMR work on AuNPs demonstrated that NMR data were obtainable for ligands on NPs with diameters up to 25 nm for the first time. This was facilitated by the strong proton NMR signals of the trimethylammonium headgroup, which are present in a distinct regime from other ligand protons' signals. Ligand density analyses showed that the smallest AuNPs (below 4 nm) had the largest ligand densities, yet spin-spin T2 measurements revealed that these smallest NPs also had the most mobile ligand headgroups. Molecular dynamics simulations were able to reconcile these seemingly contradictory results.While NMR spectroscopy provides ligand information averaged over many NPs, the ligand distribution on individual particles' surfaces must also be probed to fully understand the surface coating. Taking advantage of improvements in electron energy loss spectroscopy (EELS) detectors employed with scanning transmission electron microscopy (STEM), a single-layer graphene substrate was used to calibrate the carbon K-edge EELS signal, allowing quantitative imaging of the carbon atom densities on AuNRs with sub-nanometer spatial resolution. In collaboration with others, we revealed that the mean value for surfactant-bilayer-coated AuNRs had 10-30% reduced ligand density at the ends of the rods compared to the sides, confirming prior indirect evidence for spatially distinct ligand densities.Recent work has found that surface ligands on nanoparticles can, somewhat surprisingly, enhance the selectivity and efficiency of the electrocatalytic reduction of CO2 by controlling access to the active site, tuning its electronic and chemical environment, or denying entry to impurities that poison the nanoparticle surface to facilitate reduction. Looking to the future, while NMR and EELS are powerful and complementary techniques for investigating surface coatings on AuNPs, the frontier of this field includes the development of methods to probe the surface ligands of individual NPs in a high-throughput manner, to monitor nano-bio interactions within complex matrices, and to study structure-property relationships of AuNPs in biological systems.

Effect of shape on depth profile Nuclear Magnetic Resonance data of multilayered composite structure

ABSTRACT Polymer matrix composite structures with adhesively bonded rubber layers are being used for various industrial applications. The adhesive layer thickness (used for bonding composite and elastomer rubber layers) has to be uniform to achieve desired bond strength. However, this cannot be controlled in practical applications in industry as no physical measurements are possible for large structures. This paper reports application of single-sided portable Nuclear Magnetic Resonance (NMR) at a frequency of 12.88 MHz for the study of the adhesive layer thickness measurement as well as qualitative analysis of the adhesive layer used for bonding these materials. The effect of the shape of the sample on the proton NMR signal which is related indirectly to elastic properties was investigated. Results obtained on flat and curved glass fibre reinforced polymer (GFRP) composite samples were compared. Studies showed there is a change in single-sided NMR depth profile data (slope of amplitude versus depth curve) due to changes in the shape of the composite structure. A multilayer sample with rubber and propellant bonded adhesively to the composite structure was also tested to study the effect of shape on the profile NMR data.

The model structure of the hammerhead ribozyme formed by RNAs of reciprocal chirality.

RNA-based tools are frequently used to modulate gene expression in living cells. However, the stability and effectiveness of such RNA-based tools is limited by cellular nuclease activity. One way to increase RNA’s resistance to nucleases is to replace its D-ribose backbone with L-ribose isomers. This modification changes chirality of an entire RNA molecule to L-form giving it more chance of survival when introduced into cells. Recently, we have described the activity of left-handed hammerhead ribozyme (L-Rz, L-HH) that can specifically hydrolyse RNA with the opposite chirality at a predetermined location. To understand the structural background of the RNA specific cleavage in a heterochiral complex, we used circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy as well as performed molecular modelling and dynamics simulations of homo- and heterochiral RNA complexes. The active ribozyme-target heterochiral complex showed a mixed chirality as well as low field imino proton NMR signals. We modelled the 3D structures of the oligoribonucleotides with their ribozyme counterparts of reciprocal chirality. L- or D-ribozyme formed a stable, homochiral helix 2, and two short double heterochiral helixes 1 and 3 of D- or L-RNA strand thorough irregular Watson–Crick base pairs. The formation of the heterochiral complexes is supported by the result of simulation molecular dynamics. These new observations suggest that L-catalytic nucleic acids can be used as tools in translational biology and diagnostics.

Revealing Molecular Mechanisms in Hierarchical Nanoporous Carbon via Nuclear Magnetic Resonance

Author(s): Mao, H; Tang, J; Xu, J; Peng, Y; Chen, J; Wu, B; Jiang, Y; Hou, K; Chen, S; Wang, J; Lee, HR; Halat, DM; Zhang, B; Chen, W; Plantz, AZ; Lu, Z; Cui, Y; Reimer, JA | Abstract: Hierarchical nanoporous carbons combining pore sizes of different length scales are highly important for separation processes. However, critical questions remain regarding the hierarchical structure regulation and the molecular mechanisms of gaseous adsorbate uptake and interactions within the hierarchical nanoporous carbons. These materials present characterization challenges in that there are no experimental techniques that can elucidate the molecular mechanisms of the organic compounds and CO within the materials. We deployed multidimensional solid-state nuclear magnetic resonance (NMR) to generate maps of guest-framework interactions as a function of adsorbate concentrations and adsorption times. The NMR spectra provide insight toward the design of effective hierarchical pore structures. Our materials show a high volatile organic compounds/CO physisorption capacity, which reveals promising application to carbon-capture strategies to mitigate global warming. 2 2

OBETICHOLIC ACID: AN INSIGHT INTO A QUANTITATIVE DETERMINATION AND METHODOLOGICAL VALIDATION THROUGH NUCLEAR MAGNETIC RESONANCE

Objective: The research work unveils the use of nuclear magnetic resonance (NMR) technique for quantitative determination and method validation of obeticholic acid. As standard expository methodology for more up to date medications or formulations may not be available in pharmacopeias, hence it is fundamental need to create novel analytical procedures which should be precise and accurate.
 Methods: Proton (1H) and carbon (13C) NMR analysis were initially performed to confirm the preliminary authenticity of obeticholic acid API. Method validation was accomplished on the basis of standard guidelines for the parameters, in which tetramethylbenzene as an internal standard and deuterated dimethyl sulfoxide as a diluent were used to assess the obeticholic acid.
 Results: For the quantification of the drug, the proton nuclear magnetic resonance signals at 0.602 ppm and 6.86 ppm corresponding to the analyte proton of drug and internal standard respectively were used. The curve equation calculated from the regression method, the relative-standard-deviation and correlation-coefficient were found to be 0.743% and 0.9989 respectively, indicating good linearity. Consequently, the quantitative assay of the drug was found to be 99.91% in linearity with limit of detection and quantification values as 0.0773 mg and 0.2344 mg respectively, making successful the study of method validation for obeticholic acid.
 Conclusion: The advantage of the method was that no reference standard of analyte drug was required for quantification and method validation. The method is non-destructive and can be applied for quantification of drug in commercial pharmaceutical formulation products.

Spectroscopic measurements of metabolic fluxes

The conversion of a deuterated substrate into cellular metabolites in vivo can be quantified via decreases in the proton nuclear magnetic resonance signals of these metabolites.

Structural and biophysical insight into dual site binding of the protoberberine alkaloid palmatine to parallel G-quadruplex DNA using NMR, fluorescence and Circular Dichroism spectroscopy

Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4, has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by 1H and 31P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra. Thermal stabilization of DNA was determined by CD, 1H NMR and Differential Scanning Calorimetry (DSC). Binding of palmatine induces 98% enhancement of fluorescence accompanied by blue shift ∼8 nm. CD spectral bands of DNA show minor changes. Diffusion NMR studies confirm formation of a stable complex. Proton NMR signals of palmatine shift upfield upon binding and NOE cross peaks of H10, H3, H28, 5OCH3 protons with T2, A3/G3, G6 and T7 residues reveal dual recognition sites in both G-quadruplex DNA sequences, resulting in thermal stabilization of G-quadruplex by ∼13–17 °C. Restrained molecular dynamics simulations using NOE distance restraints for 2:1 palmatine-[d(TTGGGGT)]4 complex reveal end-stacking of palmatine at G6pT7 step and groove binding along T2pG3 step. Binding to [d(TTAGGGT)]4 takes place at T2pA3pG4 and G6pT7 steps. Structural features of molecular recognition of two different G-quadruplex DNA sequences by palmatine have relevance in rational drug development for anti-cancer therapy.

Characterization and Differentiation of Geometric Isomers of 3-methylfentanyl Analogs by Gas Chromatography/Mass Spectrometry, Liquid Chromatography/Mass Spectrometry, and Nuclear Magnetic Resonance Spectroscopy.

The cis and trans isomers of 3-methylfentanyl and its three analogs were chemically synthesized, and these compounds were characterized and differentiated by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), and nuclear magnetic resonance (NMR) spectroscopy. The cis and trans isomers of the 3-methylfentanyl analogs were completely separated by GC/MS. Although the high temperature of the GC injection port caused thermal degradation of β-hydroxy-3-methylfentanyl, the degradation was completely suppressed by trimethylsilyl derivatization. The isomers were also well separated by LC/MS on an octadecylsilyl column with 10mM ammonium acetate and methanol as the mobile phase. The proton NMR signals were split when the hydrochloride salts of the 3-methylfentanyl analogs were dissolved in deuterated chloroform because stereoisomers were formed by the coordination of the hydrochloride proton to the nitrogen of the piperidine ring of the 3-methylfentanyl analogs.

A New Receiver Front-End for Simultaneous Dual-Frequency NMR Applications

To obtain certain information such as metabolic concentrations in neural or muscular tissues and other applications, it is necessary to design nuclear magnetic resonance (NMR) transmitters/receivers capable of operating at multiple frequencies, while maintaining a good performance at each frequencies. We have proposed a new NMR receiver front-end for simultaneous detection of proton and carbon nucleus. The system consists of two reception coils for carbon and hydrogen analysis, a multiband low-noise amplifier (LNA) for increasing the voltage level and a network for passive amplification, noise figure minimization and decreasing mutuality effect between two coils. The proposed coil set was designed, simulated and analyzed and also the signal to noise ratio (SNR) with quality factor have been calculated for it by simulation. The LNA has been designed in a 0.18[Formula: see text][Formula: see text]m CMOS technology and its gains for carbon and proton NMR signals are 45 and 48[Formula: see text]dB, respectively. The input referred noise for both signals is lower than 0.4[Formula: see text]nV/sqrt(Hz) and the power consumption is 4 mA from a single 1.8[Formula: see text]V supply.

A metabolomic profile is associated with the risk of incident coronary heart disease

Metabolomics, defined as the comprehensive identification and quantification of low-molecular-weight metabolites to be found in a biological sample, has been put forward as a potential tool for classifying individuals according to their risk of coronary heart disease (CHD). Here, we investigated whether a single-point blood measurement of the metabolome is associated with and predictive for the risk of CHD. We obtained proton nuclear magnetic resonance spectra in 79 cases who developed CHD during follow-up (median 8.1 years) and in 565 randomly selected individuals. In these spectra, 100 signals representing 36 metabolites were identified. Applying least absolute shrinkage and selection operator regression, we defined a weighted metabolite score consisting of 13 proton nuclear magnetic resonance signals that optimally predicted CHD. This metabolite score, including signals representing a lipid fraction, glucose, valine, ornithine, glutamate, creatinine, glycoproteins, citrate, and 1.5-anhydrosorbitol, was associated with the incidence of CHD independent of traditional risk factors (TRFs) (hazard ratio 1.50, 95% CI 1.12-2.01). Predictive performance of this metabolite score on its own was moderate (C-index 0.75, 95% CI 0.70-0.80), but after adding age and sex, the C-index was only modestly lower than that of TRFs (C-index 0.81, 95% CI 0.77-0.85 and C-index 0.82, 95% CI 0.78-0.87, respectively). The metabolite score was also associated with prevalent CHD independent of TRFs (odds ratio 1.59, 95% CI 1.19-2.13). A metabolite score derived from a single-point metabolome measurement is associated with CHD, and metabolomics may be a promising tool for refining and improving the prediction of CHD.

Structural basis of sodium–potassium exchange of a human telomeric DNA quadruplex without topological conversion

Understanding the mechanism of Na+/K+-dependent spectral conversion of human telomeric G-quadruplex (G4) sequences has been limited not only because of the structural polymorphism but also the lack of sufficient structural information at different stages along the conversion process for one given oligonucleotide. In this work, we have determined the topology of the Na+ form of Tel23 G4, which is the same hybrid form as the K+ form of Tel23 G4 despite the distinct spectral patterns in their respective nuclear magnetic resonance (NMR) and circular dichroism spectra. The spectral difference, particularly the well-resolved imino proton NMR signals, allows us to monitor the structural conversion from Na+ form to K+ form during Na+/K+ exchange. Time-resolved NMR experiments of hydrogen–deuterium exchange and hybridization clearly exclude involvement of the global unfolding for the fast Na+/K+ spectral conversion. In addition, the K+ titration monitored by NMR reveals that the Na+/K+ exchange in Tel23 G4 is a two-step process. The addition of K+ significantly stabilizes the unfolding kinetics of Tel23 G4. These results offer a possible explanation of rapid spectral conversion of Na+/K+ exchange and insight into the mechanism of Na+/K+ structural conversion in human telomeric G4s.

Long lived NMR signal in bone

Solids and rigid tissues, such as bone, ligaments, and tendons, typically appear dark in MRI, which is due to the extremely short-lived proton nuclear magnetic resonance signals. This short lifetime is due to strong dipolar interactions between immobilized proton spins, which render it challenging to detect these signals with sufficient resolution and sensitivity. Here we show the possibility of exciting long-lived signals in cortical bone tissue with a signature consistent with that of bound water signals. It is further shown that dipolar coupling networks are an integral requirement for the excitation of these long-lived signals. The use of these signals could enhance the ability to visualize rigid tissues and solid samples with high resolution and sensitivity via MRI.

Magnetic properties and spin dynamics of3d−4fmolecular complexes

We present the magnetic properties of three recently synthesized binuclear molecular complexes [NiNd], [NiGd], and [ZnGd] investigated by dc magnetization and proton nuclear magnetic resonance (NMR) measurements. The high-temperature magnetic properties are related to the independent paramagnetic behavior of the two magnetic metal ions within the binuclear entities both in [NiNd] and [NiGd]. On lowering the temperature, the formation of a magnetic dimer, with a low-spin ground state due to antiferromagnetic interaction ($J$/${k}_{B}$ \ensuremath{\approx} \ensuremath{-}25 K) between Ni${}^{2+}$ and Nd${}^{3+}$, is found in the case of [NiNd], while in [NiGd], a ferromagnetic interaction ($J$/${k}_{B}$ \ensuremath{\approx} 3.31 K) between the magnetic ions leads to a high-spin ($S$ $=$ 9/2) ground state. The temperature dependence of the proton nuclear spin lattice relaxation rate ${T}_{1}$${}^{\ensuremath{-}1}$ in [NiNd] is driven by the fluctuation of the hyperfine field at the nuclear site due to relaxation of the magnetization. At high temperatures, the independent Ni${}^{2+}$ and Nd${}^{3+}$ spins fluctuate fast, while at low temperatures, we observe a slowing down of the fluctuation in the total magnetization of the dimer because of the insurgence of antiferromagnetic spin correlations. The relaxation mechanism in [NiNd] at low temperatures is interpreted by a single temperature-dependent correlation frequency ${\ensuremath{\omega}}_{\mathrm{c}}$ \ensuremath{\propto} ${T}^{3.5}$, which reflects the lifetime broadening of the exchange-coupled spins via spin-phonon interaction. The proton NMR signal in [NiGd] could just be detected at room temperature due to the shortening of relaxation times when $T$ is decreased. The magnetic properties of [ZnGd] are the ones expected from a weakly interacting assembly of isolated moments except for anomalies in the susceptibility and NMR results below 15 K, which currently cannot be explained.

A Possible Role of Water in the Protein Folding Process

The thermal folding of hydrated lysozyme has been investigated by means of the high resolution nuclear magnetic resonance (NMR) technique. The proton NMR signal belonging to the biomolecule hydration water (hydration level h = 0.3) was analyzed with the aim to explore the protein structural changes as well as to verify if water plays a role in this biological basic phenomenon. In such a way, we studied the proton chemical shift and the "apparent spin-spin relaxation time" for which water molecules assume the role of system probes in a situation in which the limited hydration of a solid-globular lyophilized protein sample (covering on average the first hydration shell) enables data interpretation devoid of complications arising from bulk water. The study was performed by means of proper temperature changes, different warming and cooling cycles, that starting from the protein in the native state explore the reversible and the irreversible phases of the denaturation. The obtained results confirm that water as a "local probe" follows accurately all the protein behaviors, detailing properly its structural and dynamical changes in this transition, from native to denatured. Since the water chemical shift, as proposed by commonly accepted theoretical and MD simulations findings, is linked to the hydrogen bond (HB) interactions, the obtained data suggest that the denaturation process is related to the average number of bonds in which the water molecules are involved.

On the feasibility of neurocurrent imaging by low-field nuclear magnetic resonance

We describe a nuclear magnetic resonance (NMR) spectrometer operating at 20 μT with a frequency resolution of 2 mHz to determine the intrinsic linewidth of the proton resonance in the human brain to be about 3 Hz. Using the same system we measured a biomagnetic field of 0.5 to 1 pT amplitude, which was generated by sustained brain activity evoked during repetitive median nerve stimulation. From these data, the effect of neuronal currents on the proton NMR signal was estimated. We conclude that neuronal currents may cause a measurable shift of the proton NMR line of brain tissue in low-fields.

Single-File Diffusion of Confined Water Inside SWNTs: An NMR Study

We report a nuclear magnetic resonance (NMR) study of confined water inside approximately 1.4 nm diameter single-walled carbon nanotubes (SWNTs). We show that the confined water does not freeze even up to 223 K. A pulse field gradient (PFG) NMR method is used to determine the mean squared displacement (MSD) of the water molecules inside the nanotubes at temperatures below 273 K, where the bulk water outside the nanotubes freezes and hence does not contribute to the proton NMR signal. We show that the mean squared displacement varies as the square root of time, predicted for single-file diffusion in a one-dimensional channel. We propose a qualitative understanding of our results based on available molecular dynamics simulations.

Overhauser Dynamic Nuclear Polarization To Study Local Water Dynamics

Surface and internal water dynamics of molecules and soft matter are of great relevance to their structure and function, yet the experimental determination under ambient and steady-state conditions is challenging. One of the most powerful approaches to measure local water dynamics within 5 A distances is to utilize the modulation of the nuclear spin relaxation rate of water protons through their time-dependent dipolar coupling to paramagnetic probes, here nitroxide spin labels. We recently introduced a method to obtain local water dynamics through Overhauser dynamic nuclear polarization (DNP). This has a unique advantage over other related techniques available in that a highly amplified proton nuclear magnetic resonance signal carries the information, allowing the use of minute microliter sample volumes and 100 muM sample concentrations. The outcome of our approach is the quantitative determination of the key DNP parameter known as the coupling factor, which provides local translational diffusion dynamics of the solvent within 5 A of the spin label. In contrast to recent reports that the coupling factor for nitroxide radicals cannot be quantified due to the difficulty in determining the saturation factor for the spin label, we show the saturation factor can be accurately determined and for the first time present agreement between measurements and theory. We discuss the discrepancy between the related field cycling relaxometery technique and DNP in determining the coupling factor and present arguments in support of the DNP-determined value. DNP measurements of local hydration dynamics around nitroxides in bulk water and on the surface of proteins are presented.

Pore size distributions in polyelectrolyte multilayers determined by nuclear magnetic resonance cryoporometry

Polyelectrolyte multilayers (PEMs) are thin films, which are assembled one molecular layer at a time, by alternatingly adsorbing polycations and polyanions making use of their attractive electrostatic interaction. Since the porosity of PEMs is one of the properties of major interest, in the current work the first pore size distribution of PEMs in samples consisting of silica particles coated with poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) is presented. To this end, the nuclear magnetic resonance (NMR) cryoporometry technique was applied. The proton NMR signal of liquid water is analyzed assuming a log normal distribution of motional correlation times. From the results, it is possible to determine the size of water sites in the layers to around 1 nm. In addition, a slight variation with the number of layers is found. The average pore size agrees with cutoff sizes found in permeation experiments.

Mapping the parameter space of a T2-dependent model of water diffusion MR in brain tissue

We present a new model for describing the diffusion-weighted (DW) proton nuclear magnetic resonance signal obtained from normal grey matter. Our model is analytical and, in some respects, is an extension of earlier model schemes. We model tissue as composed of three separate compartments with individual properties of diffusion and transverse relaxation. Our study assumes slow exchange between compartments. We attempt to take cell morphology into account, along with its effect on water diffusion in tissues. Using this model, we simulate diffusion-sensitive MR signals and compare model output to experimental data from human grey matter. In doing this comparison, we perform a global search for good fits in the parameter space of the model. The characteristic nonmonoexponential behavior of the signal as a function of experimental b value is reproduced quite well, along with established values for tissue-specific parameters such as volume fraction, tortuosity and apparent diffusion coefficient. We believe that the presented approach to modeling diffusion in grey matter adds new aspects to the treatment of a longstanding problem.