Nuclear Magnetic Resonance Instrument Research Articles

Two-dimensional Nuclear Magnetic Resonance Spectroscopy with Parallel Acquisition of 1H-1H and 19F-19F Correlations

A pulse sequence was established to obtain the two-dimensional nuclear magnetic resonance (NMR) spectroscopy with parallel acquisition of 1H-1H and 19F-19F correlations (1H/19F PANSY-COSY) using a 600 MHz Agilent Direct Drive II NMR instrument equipped with a triple resonance HFX probe feeding 1H and 19F receiver channels independently. The results of homo-nuclear COSY experiments on 4,4,5,5,6,6,7,7,7-nonafluoro-1-heptanol provided simultaneously 1H-1H and 19F-19F correlation spectra, which were compared with the regular COSY spectra acquired under the same conditions. The 1H/19F PANSY-COSY data showed the same resolution and signal sensitivity as the regular 1H-1H COSY and 19F-19F COSY while saving 40% of the experiment time. To improve the resolution for 1H/19F PANSY-COSY signals along the indirectly detection dimension, a narrow spectral window was set up in favor of the 1H chemical shifts range. The resulted 19F-19F COSY signals were folded along the indirectly detection dimension, and the spectra quality was improved.

NPK NMR Sensor: Online Monitoring of Nitrogen, Phosphorus, and Potassium in Animal Slurry.

Knowledge of the actual content of nitrogen, phosphorus, and potassium (NPK) in animal slurry is highly important to optimize crop production and avoid environmental pollution when slurry is spread on agricultural fields. Here, we present a mobile, low-field nuclear magnetic resonance (NMR) sensor suitable for online monitoring of the NPK content in animal slurry as an alternative to crude estimates or tedious nonspecific, off-site laboratory analysis. The sensor is based on (14)N, (17)O, (31)P, and (39)K NMR in a digital NMR instrument equipped with a 1.5 T Halbach magnet for direct detection of ammonium N, total P, and K and indirect evaluation of the organic N content, covering all practical components of NPK in animal slurry. In correlation studies, the obtained NMR measurements show good agreement with reference measurements from commercial laboratories.

Online monitoring of fermentation processes via non-invasive low-field NMR.

For the development of biotechnological processes in academia as well as in industry new techniques are required which enable online monitoring for process characterization and control. Nuclear magnetic resonance (NMR) spectroscopy is a promising analytical tool, which has already found broad applications in offline process analysis. The use of online monitoring, however, is oftentimes constrained by high complexity of custom-made NMR bioreactors and considerable costs for high-field NMR instruments (>US$200,000). Therefore, low-field (1) H NMR was investigated in this study in a bypass system for real-time observation of fermentation processes. The new technique was validated with two microbial systems. For the yeast Hansenula polymorpha glycerol consumption could accurately be assessed in spite of the presence of high amounts of complex constituents in the medium. During cultivation of the fungal strain Ustilago maydis, which is accompanied by the formation of several by-products, the concentrations of glucose, itaconic acid, and the relative amount of glycolipids could be quantified. While low-field spectra are characterized by reduced spectral resolution compared to high-field NMR, the compact design combined with the high temporal resolution (15 s-8 min) of spectra acquisition allowed online monitoring of the respective processes. Both applications clearly demonstrate that the investigated technique is well suited for reaction monitoring in opaque media while at the same time it is highly robust and chemically specific. It can thus be concluded that low-field NMR spectroscopy has a great potential for non-invasive online monitoring of biotechnological processes at the research and practical industrial scales.

Model-free estimation of the effective correlation time for C-H bond reorientation in amphiphilic bilayers: (1)H-(13)C solid-state NMR and MD simulations.

Molecular dynamics (MD) simulations give atomically detailed information on structure and dynamics in amphiphilic bilayer systems on timescales up to about 1 μs. The reorientational dynamics of the C-H bonds is conventionally verified by measurements of (13)C or (2)H nuclear magnetic resonance (NMR) longitudinal relaxation rates R1, which are more sensitive to motional processes with correlation times close to the inverse Larmor frequency, typically around 1-10 ns on standard NMR instrumentation, and are thus less sensitive to the 10-1000 ns timescale motion that can be observed in the MD simulations. We propose an experimental procedure for atomically resolved model-free estimation of the C-H bond effective reorientational correlation time τe, which includes contributions from the entire range of all-atom MD timescales and that can be calculated directly from the MD trajectories. The approach is based on measurements of (13)C R1 and R1ρ relaxation rates, as well as (1)H-(13)C dipolar couplings, and is applicable to anisotropic liquid crystalline lipid or surfactant systems using a conventional solid-state NMR spectrometer and samples with natural isotopic composition. The procedure is demonstrated on a fully hydrated lamellar phase of 1-palmitoyl-2-oleoyl-phosphatidylcholine, yielding values of τe from 0.1 ns for the methyl groups in the choline moiety and at the end of the acyl chains to 3 ns for the g1 methylene group of the glycerol backbone. MD simulations performed with a widely used united-atom force-field reproduce the τe-profile of the major part of the acyl chains but underestimate the dynamics of the glycerol backbone and adjacent molecular segments. The measurement of experimental τe-profiles can be used to study subtle effects on C-H bond reorientational motions in anisotropic liquid crystals, as well as to validate the C-H bond reorientation dynamics predicted in MD simulations of amphiphilic bilayers such as lipid membranes.

Comparative study of helical-cut notch–coil magnets for fast-field-cycling nuclear magnetic resonance

In this manuscript we describe an α-helical-cut notch–coil magnet system designed for fast switching of the magnetic field. An attempt was made to determine the extent to which such a magnet configuration can be efficiently used for fast-field-cycling (FFC) nuclear magnetic resonance (NMR) instruments. In addition to the typical technical requirements (high field-to-power ratio, adequate electric performance for fast-switching of the magnetic field and NMR-compatible magnetic field homogeneity), a tunable homogeneity within the sample volume and more uniform heat dissipation along the magnet body are included. A helical-cut notch–coil machined in metallic cylinders with external movable pieces was found to fit these requirements very well. A key factor for the optimization of the magnet parameters is the use of a novel calculation procedure based on a more realistic model that consider a magnet geometry with broken azimuthal symmetry. The aim of this paper is to theoretically compare the proposed geometry with other existing designs. No particular prototype is presented here. A clear understanding of the notch–coil performance was found to be an essential step for its further consideration as a potential autoadaptive (electronically controlled) magnet system for FFC applications.

Agilent To Exit NMR Business

Agilent Technologies is shutting down its struggling nuclear magnetic resonance instrumentation business and eliminating 300 jobs in Yarnton, England, and Santa Clara, Calif. “This action is a step...

Stone porosity, wettability changes and other features detected by MRI and NMR relaxometry: a more than 15-year study.

Scientists applying magnetic resonance techniques to cultural heritage are now a quite vast and international community, even if these applications are not yet well known outside this community. Not only laboratory experiments but also measurements in the field are now possible, with the use of portable nuclear magnetic resonance (NMR) instruments that enable non-invasive and non-destructive studies on items of any size, of high artistic and historical value as well as diagnosis of their conservation state. The situation was completely different in the second half of the 1990s when our group started working on applications of NMR to cultural heritage, by combining the knowledge of NMR for fluids in porous media at the University of Bologna, with the skilfulness of the chemists for cultural heritage of CNR and University of Florence, and Safeguarding Cultural Heritage Department of Aosta. Since then, our interest has been mainly devoted to develop methods to study the structure of pore space and their changes as a result of the decay, as well as to evaluate performance of the protective and conservative treatments of porous materials like stone, ceramic, cements and wood. In this paper, we will review the pathway that led us from the first tentative experiments, in the second half of the 1990s to the current work on these topics.

Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study.

The metabo-ring initiative brought together five nuclear magnetic resonance instruments (NMR) and 11 different mass spectrometers with the objective of assessing the reliability of untargeted metabolomics approaches in obtaining comparable metabolomics profiles. This was estimated by measuring the proportion of common spectral information extracted from the different LCMS and NMR platforms. Biological samples obtained from 2 different conditions were analysed by the partners using their own in-house protocols. Test #1 examined urine samples from adult volunteers either spiked or not spiked with 32 metabolite standards. Test #2 involved a low biological contrast situation comparing the plasma of rats fed a diet either supplemented or not with vitamin D. The spectral information from each instrument was assembled into separate statistical blocks. Correlations between blocks (e.g., instruments) were examined (RV coefficients) along with the structure of the common spectral information (common components and specific weights analysis). In addition, in Test #1, an outlier individual was blindly introduced, and its identification by the various platforms was evaluated. Despite large differences in the number of spectral features produced after post-processing and the heterogeneity of the analytical conditions and the data treatment, the spectral information both within (NMR and LCMS) and across methods (NMR vs. LCMS) was highly convergent (from 64 to 91 % on average). No effect of the LCMS instrumentation (TOF, QTOF, LTQ-Orbitrap) was noted. The outlier individual was best detected and characterised by LCMS instruments. In conclusion, untargeted metabolomics analyses report consistent information within and across instruments of various technologies, even without prior standardisation.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-014-0740-0) contains supplementary material, which is available to authorized users.

The Preparation of N-Heptyl Pyridine Tetrafluoroborate

The halogenated hydrocarbon and pyridine are used in the synthesis of room temperature ionic liquid intermediates bromided N-heptyl pyridine HEPB, and the nuclear magnetic resonance instrument and the intermediate infrared spectrometer are used in chemical structure characterization, so it is determined that the synthesis is the room temperature ionic intermediates HEPB. We use differential scanning calorimetric method for the determination of HEPB melting point and enthalpy change. We use the double decomposition reaction of HEPB and NaBF4in acetone for the synthesis of HEP-BF4ionic liquids. We use infrared spectrometer for the structure characterization, it is proved that we have gotten HEP-BF4room temperature ionic liquids. Solvent polarity and acid alkali both will have an influence on ultraviolet spectrum diagram displacement of room temperature ionic liquid, so in the research of ultraviolet spectrum diagram of ionic liquids and other solvent mixed solution, it is necessary to indicate which solvent is used.

The Synthesis and Characterization of N-Propyl Pyridine Tetrafluoroborate

The halogenated hydrocarbon and pyridine are used in the synthesis of room temperature ionic liquid intermediates bromided N-propyl pyridine PPB, and the nuclear magnetic resonance instrument and the intermediate infrared spectrometer are used in chemical structure characterization, so it is determined that the synthesis is the room temperature ionic intermediates PPB. We use differential scanning calorimetric method for the determination of PPB melting point and enthalpy change. We use the double decomposition reaction of PPB and NaBF4in acetone for the synthesis of PP-BF4ionic liquids. We use infrared spectrometer for the structure characterization, it is proved that we have gotten PP-BF4room temperature ionic liquids. Solvent polarity and acid alkali both will have an influence on ultraviolet spectrum diagram displacement of room temperature ionic liquid, so in the research of ultraviolet spectrum diagram of ionic liquids and other solvent mixed solution, it is necessary to indicate which solvent is used.

Characterizing protein-glycosaminoglycan interactions using solution NMR spectroscopy.

Solution nuclear magnetic resonance (NMR) spectroscopy and, in particular, chemical shift perturbation (CSP) titration experiments are ideally suited for characterizing the binding interface of macromolecular complexes. (1)H-(15) N-HSQC-based CSP studies have become the method of choice due to their simplicity, short time requirements, and not requiring high-level NMR expertise. Nevertheless, CSP studies for characterizing protein-glycosaminoglycan (GAG) interactions have been challenging due to binding-induced aggregation/precipitation and/or poor quality data. In this chapter, we discuss how optimizing experimental variables such as protein concentration, GAG size, and sensitivity of NMR instrumentation can overcome these roadblocks to obtain meaningful structural insights into protein-GAG interactions.

Precision high-throughput proton NMR spectroscopy of human urine, serum, and plasma for large-scale metabolic phenotyping.

Proton nuclear magnetic resonance (NMR)-based metabolic phenotyping of urine and blood plasma/serum samples provides important prognostic and diagnostic information and permits monitoring of disease progression in an objective manner. Much effort has been made in recent years to develop NMR instrumentation and technology to allow the acquisition of data in an effective, reproducible, and high-throughput approach that allows the study of general population samples from epidemiological collections for biomarkers of disease risk. The challenge remains to develop highly reproducible methods and standardized protocols that minimize technical or experimental bias, allowing realistic interlaboratory comparisons of subtle biomarker information. Here we present a detailed set of updated protocols that carefully consider major experimental conditions, including sample preparation, spectrometer parameters, NMR pulse sequences, throughput, reproducibility, quality control, and resolution. These results provide an experimental platform that facilitates NMR spectroscopy usage across different large cohorts of biofluid samples, enabling integration of global metabolic profiling that is a prerequisite for personalized healthcare.

Low-field NMR micro coils based on printed circuit board technology

Radiofrequency coil is one of the most important components for a nuclear magnetic resonance (NMR) instrument. In this article, some planar micro coils with an inner diameter of 2 mm and number of turns that varied from 1 to 11 were investigated based on the printed circuit board (PCB) technology. The electrical characterization of micro coils show that self-resonant frequencies are larger than 200 MHz. Then, an NMR measurement platform with a static magnetic field of 0.66 T was constructed and the signal to noise ratio (SNR) values of the NMR were analyzed. It was found that the SNR is optimal when the turn number of the micro coils is six and the excitation time of a 90° pulse is 0.8 ms. Finally, we used the micro coil with six turns to study the transverse relaxation rate of copper sulfate pentahydrate aqueous solution with different concentrations. It was found that the transverse relaxation rate is proportional to the solution concentration. Results from the micro coil were verified by measurements using a Bruker Minispec MQ60.

Monodispersed composite particles prepared via emulsifier‐free emulsion polymerization using waterborne polyurethane as microreactors

ABSTRACTMonodispersed polystyrene particles in submicrometer size were intriguingly prepared through emulsifier‐free batch‐seeded emulsion polymerization using nonmonodispersed waterborne polyurethane (WBPU) beads as microreactors. Different feed ratios of styrene (St)/WBPU for the preparation of composite particles were investigated, and the size–growth course was experimentally followed. The morphology and dispersity of the particles were characterized by scanning electron microscopy together with dynamic laser scattering particle size analyzer. Their inside structure was further characterized by transmission electron microscopy with ultramicrotomy combined with X‐ray photoelectron spectroscopy for the composite particles' surface analysis. The probable grafting polymerization of St from WBPU was verified by Fourier transform infrared spectroscopy and nuclear magnetic resonance instrument. The obtained composite particles were again employed as the seeds in the emulsion copolymerization of methyl methacrylate. As a result, the formed multilayered composite particles with reverse core–shell structure were also monodispersed and spherical. The mechanism of the formation of the monodispersed particles was proposed. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40985.

Environment-responsive nanophores for therapy and treatment monitoring via molecular MRI quenching

The effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we demonstrate that clinically approved iron oxide nanoparticles (Ferumoxytol) can be utilized to carry one or multiple drugs. These so called ‘nanophores’ retain their cargo within their polymeric coating through weak electrostatic interactions and release it in slightly acidic conditions (pH 6.8 and below). The loading of drugs increases the nanophores’ transverse T2 and longitudinal T1 NMR proton relaxation times, which is proportional to amount of carried cargo. Chemotherapy with translational nanophores is more effective than the free drug in vitro and in vivo, without subjecting the drugs or the carrier nanoparticle to any chemical modification. Evaluation of cargo incorporation and payload levels in vitro and in vivo can be assessed via benchtop magnetic relaxometers, common NMR instruments or MRI scanners.

Why is Inline NMR Rarely Used as Industrial Sensor? Challenges and Opportunities

AbstractAlthough nuclear magnetic resonance (NMR) is one of the most powerful analytical techniques, it has not been widely used as a non‐destructive, non‐contact inline industrial sensor. A short background of NMR spectroscopy fundamentals and instrumentation is presented along with its potential applications and limitations for real‐time analysis in the manufacturing sector. NMR signals are generated in the presence of a magnetic field normally produced by expensive large and heavy magnets which have been the major limiting factor in the use of NMR analysis in factories. However, the last decade has brought substantial advances in the development of cheaper, smaller, and lighter permanent magnets based on rare earth materials that use Halbach and unilateral configurations. Small and light cryogenic‐free superconducting magnets are now offered in the market and are opening a new era in manufacturing. It is expected that soon NMR spectroscopy will be applied to monitor the chemical and physical properties of complex feedstock mixtures and reactions in real time which is the ultimate goal of precise process control.

Generalized shim and gradient generation: Application to the magic angle field spinning case

A Nuclear Magnetic Resonance (NMR) instrument providing a rotating field oriented at the magic angle with the rotation axis has the potential to record high resolution NMR spectra from static heterogeneous samples exhibiting susceptibility broadening. The requirement of a high uniformity field and the possible need of imaging gradients induces several challenges in terms of shim and gradient generation. We discuss here key theoretical aspects in this context.

The Synthesis and Characterization of N-Butyl Pyridine Tetrafluoroborate

The halogenated hydrocarbon and pyridine are used in the synthesis of room temperature ionic liquid intermediates chlorinated N-butyl pyridine BPC, and the nuclear magnetic resonance instrument and the intermediate infrared spectrometer are used in chemical structure characterization, so it is determined that the synthesis is the room temperature ionic intermediates BPC. We use differential scanning calorimetric method for the determination of BPC melting point and enthalpy change. We use the double decomposition reaction of BPC and NaBF4 in acetone for the synthesis of BP-BF4ionic liquids. We use infrared spectrometer for the structure characterization, it is proved that we have gotten BP-BF4room temperature ionic liquids. Solvent polarity and acid alkali both will have an influence on ultraviolet spectrum diagram displacement of room temperature ionic liquid, so in the research of ultraviolet spectrum diagram of ionic liquids and other solvent mixed solution, it is necessary to indicate which solvent is used.

Sample Preparation of <em>Mycobacterium tuberculosis</em> Extracts for Nuclear Magnetic Resonance Metabolomic Studies

Mycobacterium tuberculosis is a major cause of mortality in human beings on a global scale. The emergence of both multi- (MDR) and extensively-(XDR) drug-resistant strains threatens to derail current disease control efforts. Thus, there is an urgent need to develop drugs and vaccines that are more effective than those currently available. The genome of M. tuberculosis has been known for more than 10 years, yet there are important gaps in our knowledge of gene function and essentiality. Many studies have since used gene expression analysis at both the transcriptomic and proteomic levels to determine the effects of drugs, oxidants, and growth conditions on the global patterns of gene expression. Ultimately, the final response of these changes is reflected in the metabolic composition of the bacterium including a few thousand small molecular weight chemicals. Comparing the metabolic profiles of wild type and mutant strains, either untreated or treated with a particular drug, can effectively allow target identification and may lead to the development of novel inhibitors with anti-tubercular activity. Likewise, the effects of two or more conditions on the metabolome can also be assessed. Nuclear magnetic resonance (NMR) is a powerful technology that is used to identify and quantify metabolic intermediates. In this protocol, procedures for the preparation of M. tuberculosis cell extracts for NMR metabolomic analysis are described. Cell cultures are grown under appropriate conditions and required Biosafety Level 3 containment, harvested, and subjected to mechanical lysis while maintaining cold temperatures to maximize preservation of metabolites. Cell lysates are recovered, filtered sterilized, and stored at ultra-low temperatures. Aliquots from these cell extracts are plated on Middlebrook 7H9 agar for colony-forming units to verify absence of viable cells. Upon two months of incubation at 37 °C, if no viable colonies are observed, samples are removed from the containment facility for downstream processing. Extracts are lyophilized, resuspended in deuterated buffer and injected in the NMR instrument, capturing spectroscopic data that is then subjected to statistical analysis. The procedures described can be applied for both one-dimensional (1D) H NMR and two-dimensional (2D) H-(13)C NMR analyses. This methodology provides more reliable small molecular weight metabolite identification and more reliable and sensitive quantitative analyses of cell extract metabolic compositions than chromatographic methods. Variations of the procedure described following the cell lysis step can also be adapted for parallel proteomic analysis.

Sample Preparation of <em>Mycobacterium tuberculosis</em> Extracts for Nuclear Magnetic Resonance Metabolomic Studies

Mycobacterium tuberculosis is a major cause of mortality in human beings on a global scale. The emergence of both multi- (MDR) and extensively-(XDR) drug-resistant strains threatens to derail current disease control efforts. Thus, there is an urgent need to develop drugs and vaccines that are more effective than those currently available. The genome of M. tuberculosis has been known for more than 10 years, yet there are important gaps in our knowledge of gene function and essentiality. Many studies have since used gene expression analysis at both the transcriptomic and proteomic levels to determine the effects of drugs, oxidants, and growth conditions on the global patterns of gene expression. Ultimately, the final response of these changes is reflected in the metabolic composition of the bacterium including a few thousand small molecular weight chemicals. Comparing the metabolic profiles of wild type and mutant strains, either untreated or treated with a particular drug, can effectively allow target identification and may lead to the development of novel inhibitors with anti-tubercular activity. Likewise, the effects of two or more conditions on the metabolome can also be assessed. Nuclear magnetic resonance (NMR) is a powerful technology that is used to identify and quantify metabolic intermediates. In this protocol, procedures for the preparation of M. tuberculosis cell extracts for NMR metabolomic analysis are described. Cell cultures are grown under appropriate conditions and required Biosafety Level 3 containment,1 harvested, and subjected to mechanical lysis while maintaining cold temperatures to maximize preservation of metabolites. Cell lysates are recovered, filtered sterilized, and stored at ultra-low temperatures. Aliquots from these cell extracts are plated on Middlebrook 7H9 agar for colony-forming units to verify absence of viable cells. Upon two months of incubation at 37 °C, if no viable colonies are observed, samples are removed from the containment facility for downstream processing. Extracts are lyophilized, resuspended in deuterated buffer and injected in the NMR instrument, capturing spectroscopic data that is then subjected to statistical analysis. The procedures described can be applied for both one-dimensional (1D) 1H NMR and two-dimensional (2D) 1H-13C NMR analyses. This methodology provides more reliable small molecular weight metabolite identification and more reliable and sensitive quantitative analyses of cell extract metabolic compositions than chromatographic methods. Variations of the procedure described following the cell lysis step can also be adapted for parallel proteomic analysis.