Desktop NMR and Its Applications From Materials Science To Organic Chemistry

NMR spectroscopy is an indispensable method of analysis in chemistry, which until recently suffered from high demands for space, high costs for acquisition and maintenance, and operational complexity. This has changed with the introduction of compact NMR spectrometers suitable for small‐molecule analysis on the chemical workbench. These spectrometers contain permanent magnets giving rise to proton NMR frequencies between 40 and 80 MHz. The enabling technology is to make small permanent magnets with homogeneous fields. Tabletop instruments with inhomogeneous fields have been in use for over 40 years for characterizing food and hydrogen‐containing materials by relaxation and diffusion measurements. Related NMR instruments measure these parameters in the stray field outside the magnet. They are used to inspect the borehole walls of oil wells and to test objects nondestructively. The state‐of‐the‐art of NMR spectroscopy, imaging and relaxometry with compact instruments is reviewed.     

Recovering Invisible Signals by Two‐Field NMR Spectroscopy

Nuclear magnetic resonance (NMR) studies have benefited tremendously from the steady increase in the strength of magnetic fields. Spectacular improvements in both sensitivity and resolution have enabled the investigation of molecular systems of rising complexity. At very high fields, this progress may be jeopardized by line broadening, which is due to chemical exchange or relaxation by chemical shift anisotropy. In this work, we introduce a two‐field NMR spectrometer designed for both excitation and observation of nuclear spins in two distinct magnetic fields in a single experiment. NMR spectra of several small molecules as well as a protein were obtained, with two dimensions acquired at vastly different magnetic fields. Resonances of exchanging groups that are broadened beyond recognition at high field can be sharpened to narrow peaks in the low‐field dimension. Two‐field NMR spectroscopy enables the measurement of chemical shifts at optimal fields and the study of molecular systems that suffer from internal dynamics, and opens new avenues for NMR spectroscopy at very high magnetic fields.     

Applicable and cost-efficient microplastic analysis by quantitative 1H-NMR spectroscopy using benchtop NMR and NoD methods

In continuation of our work on the proof-of-concept that quantitative NMR spectroscopy may be a valuable tool in microplastic (MP) analysis and quantification, we present here investigations using low-field NMR spectrometers and nondeuterated solvents for the analysis of solutions of MP particles in suitable solvents. The use of low-field NMR spectrometers (benchtop NMR) that are considerably more cost-effective in terms of purchase and operating costs compared with high-field NMR spectrometers and the use of nondeuterated solvents (NoD method) leads to an applicable and cost-efficient method for mass-based MP analysis. For benchtop 80-MHz NMR, limits of detection for polyvinylchloride (PVC), polyethylene terephthalate (PET), and polystyrene (PS) are in the same range as if a high-field 500-MHz NMR spectrometer was used for quantification (500 MHz: PET 1 μg/ml, PVC 42 μg/ml, and PS 9 μg/ml; 80 MHz: PET 4 μg/ml, PVC 19 μg/ml, and PS 21 μg/ml) for polymers being dissolved in deuterated solvents. The same is true for the corresponding limits of quantification. Moreover, it is shown for the first time that quantitative determination of the mass concentration of PET, PVC, and PS is also possible using NoD methods by evaluating the integrals of polymer-specific signals relative to an internal or external standard. Detection limits for NoD methods are in a similar range as if deuterated solvents were used (PET 2 μg/ml, PVC 39 μg/ml, and PS 8 μg/ml) using a high-field 500-MHz spectrometer or the 80-MHz spectrometer (PET 5 μg/ml).     

Profiling of thermally aged EPDM seals using portable NMR,indenter measurements and IR spectroscopy facilitating separation of different deterioration mechanisms

The changes occurring in EPDM cable transit seals during thermal ageing and the causes of these changes were investigated. Samples were aged at a temperature of 170 °C, and subsequently evaluated with respect to the distance from the surface with modulus profiling, infrared (IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy, based on the extractable mass fraction profiles for initial and aged materials. The ageing resulted in an increase in the modulus and in the degree of oxidation and in a decrease in the NMR transverse relaxation time, T₂. The NMR data were obtained in a non-invasive manner by ex situ experiments performed with a portable low-field spectrometer (NMR MOUSE). The results showed deterioration processes that can be attributed to different mechanisms i.e. oxidation, anaerobic crosslinking and migration of oil extender. The unique combination of parameter profiles made it possible to resolve and quantify these three contributing mechanisms. The NMR results highlight the potential of this method for on-site testing.     

Highly Resolved Pure-Shift Spectra on a Compact NMR Spectrometer

Benchtop NMR spectrometers experience a great success for a wide range of applications. However, their performance is highly limited by peak overlaps. Emerging “pure-shift NMR” (PS NMR) methods have been intensively used at high field to enhance the resolution by homodecoupling strategies. Here, different PS methods have been implemented on a compact NMR spectrometer operating at 43 MHz. Among the PS methods, the recent PSYCHE scheme appears more sensitive than Zangger-Sterk (ZS) experiments and offers a substantial resolution improvement as compared to 1D ¹H. On the other hand, despite their slightly lower sensitivity, ZS methods are more efficient to reduce broad signals and are more immune to strong couplings. Finally, the classical J-resolved pulse sequence is more efficient to reduce larger signals for bigger-sized molecules. The three approaches appear relevant for benchtop NMR and their combination forms an efficient toolbox to analyze a great diversity of samples.     

Fourier Transform Infrared Studies of Polymeric Materials

The recent introduction of Fourier Transform Infrared (FTIR) spectrometers that are operable over the entire IR frequency range has revitalized the field of IR spectroscopy. IR studies of complex polymeric materials that were impossible, or at least extremely difficult using conventional dispersive spectrometers, are now readily accomplished. In this review of the application of FTIR to the study of polymeric materials, we initially present a brief critical comparison of the FTIR and dispersive spectrometers followed by a discussion of the results that have been published to date.     

Extension and improvement of the methanol-d4 NMR thermometer calibration

NMR thermometers are a convenient way to determine the temperature inside the sample of an NMR spectrometer. They rely on signals with strongly temperature-dependent chemical shifts, often of OH groups; 99.8% perdeuterated methanol is an established example which is particularly well suited for modern, high-sensitivity spectrometers, but it is so far calibrated only in the range of 282 to 330 K. In this work, we extend this calibration to the entire liquid range of methanol, 175 to 338 K. Additionally, we use a temperature sensor calibrated traceably to the International Temperature Scale (ITS-90) and accounted for the magnetic field effect on the sensor, yielding a more accurate calibration curve with an uncertainty (2σ) varying between 25 and 190 mK.     

Loading‐Dependent Structural Model of Polymeric Micelles Encapsulating Curcumin by Solid‐State NMR Spectroscopy

Detailed insight into the internal structure of drug‐loaded polymeric micelles is scarce, but important for developing optimized delivery systems. We observed that an increase in the curcumin loading of triblock copolymers based on poly(2‐oxazolines) and poly(2‐oxazines) results in poorer dissolution properties. Using solid‐state NMR spectroscopy and complementary tools we propose a loading‐dependent structural model on the molecular level that provides an explanation for these pronounced differences. Changes in the chemical shifts and cross‐peaks in 2D NMR experiments give evidence for the involvement of the hydrophobic polymer block in the curcumin coordination at low loadings, while at higher loadings an increase in the interaction with the hydrophilic polymer blocks is observed. The involvement of the hydrophilic compartment may be critical for ultrahigh‐loaded polymer micelles and can help to rationalize specific polymer modifications to improve the performance of similar drug delivery systems.     

Monitoring Hydrogenation Reactions using Benchtop 2D NMR with Extraordinary Sensitivity and Spectral Resolution

Low-field benchtop nuclear magnetic resonance (BT-NMR) spectrometers with Halbach magnets are being increasingly used in science and industry as cost-efficient tools for the monitoring of chemical reactions, including hydrogenation. However, their use of low-field magnets limits both resolution and sensitivity. In this paper, we show that it is possible to alleviate these two problems through the combination of parahydrogen-induced polarization (PHIP) and fast correlation spectroscopy with time-resolved non-uniform sampling (TR-NUS). PHIP can enhance NMR signals so that substrates are easily detectable on BT-NMR spectrometers. The interleaved acquisition of one- and two-dimensional spectra with TR-NUS provides unique insight into the consecutive moments of hydrogenation reactions, with a spectral resolution unachievable in a standard approach. We illustrate the potential of the technique with two examples: the hydrogenation of ethylphenyl propiolate and the hydrogenation of a mixture of two substrates – ethylphenyl propiolate and ethyl 2-butynoate.     

Sensitivity Enhancement in Transverse Relaxation Optimized NMR Spectroscopy

Dramatically shortened transverse relaxation times in transverse relaxation optimized spectroscopy (TROSY) result from interference between dipole–dipole interactions and the anisotropy of the chemical shift. Thus NMR spectroscopy becomes a suitable method for studying large biomolecules, with optimal performance when 1-GHz spectrometers become available. By using new phase cycles and data-processing methods, the sensitivity of the TROSY experiment was increased by a factor of √2, which is of considerable importance for applications in high-field NMR studies on large proteins.     

On‐Line Monitoring of Chemical Reactions by using Bench‐Top Nuclear Magnetic Resonance Spectroscopy

Real‐time nuclear magnetic resonance (NMR) spectroscopy measurements carried out with a bench‐top system installed next to the reactor inside the fume hood of the chemistry laboratory are presented. To test the system for on‐line monitoring, a transfer hydrogenation reaction was studied by continuously pumping the reaction mixture from the reactor to the magnet and back in a closed loop. In addition to improving the time resolution provided by standard sampling methods, the use of such a flow setup eliminates the need for sample preparation. Owing to the progress in terms of field homogeneity and sensitivity now available with compact NMR spectrometers, small molecules dissolved at concentrations on the order of 1 mmol L^?1 can be characterized in single‐scan measurements with 1 Hz resolution. Owing to the reduced field strength of compact low‐field systems compared to that of conventional high‐field magnets, the overlap in the spectrum of different NMR signals is a typical situation. The data processing required to obtain concentrations in the presence of signal overlap are discussed in detail, methods such as plain integration and line‐fitting approaches are compared, and the accuracy of each method is determined. The kinetic rates measured for different catalytic concentrations show good agreement with those obtained with gas chromatography as a reference analytical method. Finally, as the measurements are performed under continuous flow conditions, the experimental setup and the flow parameters are optimized to maximize time resolution and signal‐to‐noise ratio.     

Chemical Reaction Monitoring using Zero‐Field Nuclear Magnetic Resonance Enables Study of Heterogeneous Samples in Metal Containers

We demonstrate that heterogeneous/biphasic chemical reactions can be monitored with high spectroscopic resolution using zero‐field nuclear magnetic resonance spectroscopy. This is possible because magnetic susceptibility broadening is negligible at ultralow magnetic fields. We show the two‐step hydrogenation of dimethyl acetylenedicarboxylate with para‐enriched hydrogen gas in conventional glass NMR tubes, as well as in a titanium tube. The low frequency zero‐field NMR signals ensure that there is no significant signal attenuation arising from shielding by the electrically conductive sample container. This method paves the way for in situ monitoring of reactions in complex heterogeneous multiphase systems and in reactors made of conductive materials while maintaining resolution and chemical specificity.     

Homonuclear J-Coupling Spectroscopy at Low Magnetic Fields using Spin-Lock Induced Crossing**

Nuclear magnetic resonance (NMR) spectroscopy usually requires high magnetic fields to create spectral resolution among different proton species. Although proton signals can also be detected at low fields the spectrum exhibits a single line if J-coupling is stronger than chemical shift dispersion. In this work, we demonstrate that the spectra can nevertheless be acquired in this strong-coupling regime using a novel pulse sequence called spin-lock induced crossing (SLIC). This techniques probes energy level crossings induced by a weak spin-locking pulse and produces a unique J-coupling spectrum for most organic molecules. Unlike other forms of low-field J-coupling spectroscopy, our technique does not require the presence of heteronuclei and can be used for most compounds in their native state. We performed SLIC spectroscopy on a number of small molecules at 276 kHz and 20.8 MHZ and show that the simulated SLIC spectra agree well with measurements.     

Sodium-23 Nuclear Magnetic Resonance Spectroscopy

With the availability of Fourier transform spectrometers, ²³Na-NMR spectroscopy has become an important tool. It affords direct insight into solvation and ion pairing phenomena, both in organic and in bio-inorganic systems. Monitoring the chemical shifts and linewidths of ²³Na signals gives access to binding constants, reorientational correlation times and the microdynamics of the sodium coordination shell. The binding of other cations can also be studied by ²³Na-NMR spectroscopy, in competition experiments.     

Progress in Hyperpolarized Ultrafast 2D NMR Spectroscopy

An important development in the field of NMR spectroscopy has been the advent of hyperpolarization approaches, capable of yielding nuclear spin states whose value exceeds by orders‐of‐magnitude what even the highest‐field spectrometers can afford under Boltzmann equilibrium. Included among these methods is an ex situ dynamic nuclear polarization (DNP) approach, which yields liquid‐phase samples possessing spin polarizations of up to 50 %. Although capable of providing an NMR sensitivity equivalent to the averaging of about 1 000 000 scans, this methodology is constrained to extract its “superspectrum” within a single—or at most a few—transients. This makes it a poor starting point for conventional 2D NMR acquisition experiments, which require a large number of scans that are identical to one another except for the increment of a certain t₁ delay. It has been recently suggested that by merging this ex situ DNP approach with spatially encoded “ultrafast” methods, a suitable starting point could arise for the acquisition of 2D spectra on hyperpolarized liquids. Herein, we describe the experimental principles, potential features, and current limitations of such integration between the two methodologies. For a variety of small molecules, these new hyperpolarized ultrafast experiments can, for equivalent overall durations, provide heteronuclear correlation spectra at significantly lower concentrations than those currently achievable by conventional 2D NMR acquisitions. A variety of challenges still remain to be solved before bringing the full potential of this new integrated 2D NMR approach to fruition; these outstanding issues are discussed.     

Parahydrogen‐Induced Radio Amplification by Stimulated Emission of Radiation

Radio amplification by stimulated emission of radiation (RASER) was recently discovered in a low‐field NMR spectrometer incorporating a highly specialized radio‐frequency resonator, where a high degree of proton‐spin polarization was achieved by reversible parahydrogen exchange. RASER activity, which results from the coherent coupling between the nuclear spins and the inductive detector, can overcome the limits of frequency resolution in NMR. Here we show that this phenomenon is not limited to low magnetic fields or the use of resonators with high‐quality factors. We use a commercial bench‐top 1.4 T NMR spectrometer in conjunction with pairwise parahydrogen addition producing proton‐hyperpolarized molecules in the Earth's magnetic field (ALTADENA condition) or in a high magnetic field (PASADENA condition) to induce RASER without any radio‐frequency excitation pulses. The results demonstrate that RASER activity can be observed on virtually any NMR spectrometer and measures most of the important NMR parameters with high precision.     

Consolidated silica glass from nanoparticles

A dense silica glass was prepared by consolidating a highly dispersed silicic acid powder (particle size <10 nm) with the Spark Plasma Sintering (SPS) technique. The glass was characterized by ellipsometry, transmission electron microscopy (TEM), infrared reflectance and transmittance spectroscopy, as well as by Raman, UV-Vis-NIR and solid-state nuclear magnetic resonance (NMR) spectroscopy. The prototypic sample showed a transmittance of about 63% compared to silica glass in the UV-Vis spectral range. Based on the results of infrared transmittance spectroscopy this lower transparency is due to the comparably high water content, which is about 40 times higher than that in silica glass. ¹H magic-angle spinning (MAS) NMR confirmed an increase in hydroxyl groups in the sample prepared by SPS relative to that of the conventional SiO₂ reference glass. Aside from the comparably high water content, we conclude from the similarity of the IR-reflectance and the ²⁹Si MAS NMR spectra of the SPS sample and the corresponding spectra of the conventionally prepared silica glass, that the short- and medium-range order is virtually the same in both materials. Raman spectroscopy, however, suggests that the number of three- and four-membered rings is significantly smaller in the SPS sample compared to the conventionally prepared sample. Based on these results we conclude that it is possible to prepare glasses by compacting amorphous powders by the SPS process. The SPS process may therefore enable the preparation of glasses with compositions inaccessible by conventional methods.     

核磁共振法研究固体表面上的吸附

应用JEOL FX-90Q NMR谱仪测定了吸附在NaY分子筛,氧化铝,二氧化硅上的四甲基硅烷和正己烷的核磁氢谱和碳谱.结果表明,在一些吸附体系的研究中,现有仪器适用于液体样品,以氢谱和碳谱比较发现碳谱在分辨率分方面较之氢谱有几个优点,顺磁杂质对谱线宽度有明显影响.在NaY分子筛上预先吸附氢以后再吸附乙烯,其吸附速率低于未吸附氢的样品.     

µ-NMR at the point of care testing

NMR shows strong analytical capability for obtaining molecular information on materials and is used in a variety of fields. Micro-NMR (µNMR) is mainly based on low-field NMR (LF-NMR), which makes NMR detection portable and inexpensive. Point-of-care testing (POCT) has gradually become an area of major concern, and scientists have made much progress in applying µNMR systems for POCT. To the best of our knowledge, this is the first review of the latest development in miniaturization of µNMR systems. Then, we discuss cutting-edge µNMR-based applications in POCT and the outlook for future developments.     

Longitudinal Relaxation Optimization Enhances 1H-Detected HSQC in Solid-State NMR Spectroscopy on Challenging Biological Systems

Solid-state (SS) NMR spectroscopy is a powerful technique for studying challenging biological systems, but it often suffers from low sensitivity. A longitudinal relaxation optimization scheme to enhance the signal sensitivity of HSQC experiments in SSNMR spectroscopy is reported. Under the proposed scheme, the ¹H spins of ¹H–X (¹⁵N or ¹³C) are selected for signal acquisition, whereas other vast ¹H spins are flipped back to the axis of the static magnetic field to accelerate the spin recovery of the observed ¹H spins, resulting in enhanced sensitivity. Three biological systems are used to evaluate this strategy, including a seven-transmembrane protein, an RNA, and a whole-cell sample. For all three samples, the proposed scheme largely shortens the effective ¹H longitudinal relaxation time and results in a 1.3–2.5-fold gain in sensitivity. The selected systems are representative of challenging biological systems for observation by means of SSNMR spectroscopy; thus indicating the general applicability of this method, which is particularly important for biological samples with a short lifetime or with limited sample quantities.