High-Sensitivity NMR Probe Systems

Review: 194 refs.

Dynamic nuclear polarization (DNP) is a nuclear magnetic resonance (NMR) hyperpolarization technique that mediates polarization transfer from unpaired electrons with large thermal polarization to NMR-active nuclei via microwave (mw) irradiation. The ability to generate arbitrarily shaped mw pulses using arbitrary waveform generators allows for remarkable improvement of the robustness and versatility of DNP. We present here novel design principles based on single-spin vector effective Hamiltonian theory to develop new broadband DNP pulse sequences, namely, an adiabatic version of XiX (X–inverse X)–DNP and a broadband excitation by amplitude modulation (BEAM)–DNP experiment. We demonstrate that the adiabatic BEAM-DNP pulse sequence may achieve a 1H enhancement factor of ∼360, which is better than ramped-amplitude NOVEL (nuclear spin orientation via electron spin locking) at ∼0.35 T and 80 K in static solids doped with trityl radicals. In addition, the bandwidth of the BEAM-DNP experiments (~50 MHz) is about three times the 1H Larmor frequency. The generality of our theoretical approach will be helpful in the development of new pulsed DNP sequences.

Understanding the kinetics of proteins interacting with their ligands is important for characterizing molecular mechanism. However, it can be difficult to determine the extent and nature of these interactions for weakly formed protein-ligand complexes that have lifetimes of micro- to milliseconds. Nuclear magnetic resonance (NMR) spectroscopy is a powerful solution-based method for the atomic-level analysis of molecular interactions on a wide range of timescales, including micro- to milliseconds. Recently the combination of thermodynamic experiments using isothermal titration calorimetry (ITC) with kinetic measurements using ZZ-exchange and CPMG relaxation dispersion NMR spectroscopy have been used to determine the kinetics of weakly interacting protein systems. This chapter describes the application of ITC and NMR to understand the differences in the kinetics of carbohydrate binding by the β1- and β2-carbohydrate-binding modules of AMP-activated protein kinase.

We describe a new triply tuned (e−, 1H, and 13C) resonance structure operating at an electron Larmor frequency of 139.5 GHz for dynamic nuclear polarization (DNP) and electron nuclear double-resonance (ENDOR) experiments. In contrast to conventional double-resonance structures, the body of the microwave cavity simultaneously acts as a NMR coil, allowing for increased efficiency of radiofrequency irradiation while maintaining a high quality factor for microwave irradiation. The resonator design is ideal for low-γ-nuclei ENDOR, where sensitivity is limited by the fact that electron spin relaxation times are on the order of the RF pulse lengths. The performance is demonstrated with 2H ENDOR on a standard perdeuterated bis-diphenylene-phenyl-allyl stable radical. In DNP experiments, we show that the use of this resonator, combined with a low microwave power setup (17 mW), leads to significantly higher 1H signal enhancement (ϵ ∼ 400 ± 50) than previously achieved at 5-T fields. The results emphasize the importance of optimizing the microwave B1 field by improving either the quality factor of the microwave resonator or the microwave power level.

Nuclear magnetic resonance (NMR) has been broadly investigated and applied in many industries (e.g., medical treatment, food safety and materials) as a powerful approach to explore the internal structure and composition of substances. However, the need for more sensitivity has been one of the most severe problems hindering the practical application of NMR. This paper suggests various approaches to deal with this defect, from adjusting factors based on the theoretical principle to the progressive hyperpolarization method. Classified by polarization sources, several representative sub-fields of hyperpolarization are further interpreted and analyzed, including Dynamic Nuclear Polarization (DNP), Optical Pumping (OP) and Parahydrogen Induced Polarization (PHIP). Based on the analysis and prospect of the aforementioned feasible methods, the main factors that restrict the sensitivity of NMR will be identified. Moreover, the prospects and new technologies brought by the methods based on different theoretical foundations have been considered to improve these factors and make NMR apply to a broader range of fields. Overall, these results not only indicate the current research status but also shed light on guiding further exploration of methods of enhancing NMR sensitivity and usability.

Paul Christian Lauterbur

Zero- and ultralow-field (ZULF) nuclear magnetic resonance (NMR) is an emerging tool for precision chemical analysis. Unlike conventional (high-field) NMR, which relies on chemical shifts for molecular identification, zero-field analog reports J-spectra that depend on the nuclear spin-spin coupling topology of molecules under investigation. While chemical shifts are usually a small fraction of the resonance frequencies, J-spectra for various spin systems are completely different from each other. In this work, we use zero-field NMR to study dynamic chemical processes and investigate the influence of chemical exchange on ZULF NMR spectra. We develop a computation approach that allows quantitative calculation of ZULF NMR spectra in the presence of chemical exchange and apply it to study aqueous solutions of [15N]ammonium as a model system. In this system, proton exchange rates span more than three orders of magnitude depending on acidity (pH), as monitored by high-field and ZULF NMR. We show that chemical exchange substantially affects the J-coupled NMR spectra and, in some cases, can lead to degradation and complete disappearance of the spectral features. To demonstrate potential applications of ZULF NMR for chemistry and biomedicine, we show a ZULF NMR spectrum of [2-13C]pyruvic acid hyperpolarized via dissolution dynamic nuclear polarization (dDNP). The metabolism of pyruvate provides valuable biochemical information and its monitoring by zero-field NMR could give spectral resolution that is hard to achieve at high magnetic fields. We foresee applications of affordable and scalable ZULF NMR coupled with hyperpolarization modalities to study chemical exchange phenomena in vivo and in situations where high-field NMR detection is not possible to implement.

A Spectrometer for Dynamic Nuclear Polarization and Electron Paramagnetic Resonance at High Frequencies

Despite extensive research conducted on plating and dendrite formation in lithium batteries, the molecular formation processes are not yet fully understood. Electron paramagnetic resonance (EPR) sensitively detects metallic Li species but misses non-paramagnetic ones. Nuclear magnetic resonance (NMR) is chemically selective, yet exhibits low sensitivity under low-field conditions. Dynamic nuclear polarization (DNP) overcomes this by transferring electron spin polarization to nuclei. Here, correlative EPR and DNP-enhanced NMR of lithium on copper is demonstrated using a custom setup operating at 0.34 T with a sweepable electromagnet. DNP experiments were conducted in pulsed mode to minimize sample heating. The resulting enhanced NMR signal allows the observation of electrochemically deposited lithium on copper, harvested from a Cu vs. Li cell, with an enhancement 400$$\\end{document}]]>. By changing the magnetic field strength by a few Gauss, the saturation of the conduction EPR transition was varied, leading to an altered Knight shift of metallic . The corresponding change of the DNP-polarized chemical shifts in the range from 240 ppm to 80 ppm allowed an indirect, saturation-based distinction of EPR species. Moreover, an enhancement by a factor of about 2 of the H signal from the surrounding electrolyte of electrochemically deposited lithium was observed, indicating the potential to investigate the solid–electrolyte interface (SEI). The setup employed a battery cell housing developed for EPR, demonstrating its suitability for in operando experiments in the future.

Proton Dynamic Nuclear Polarization (DNP) experiments were conducted on a 3.4 T homebuilt hybrid pulsed-EPR-NMR spectrometer, on static samples containing 10 mM or 40 mM TEMPOL in frozen glassy solutions of DMSO/water. During DNP experiments proton-NMR signals are enhanced with the help of microwave (MW) irradiation on or close to the Electron Paramagnetic Resonance (EPR) spectrum of the free radicals in the sample, transferring polarization from the free electrons to the nuclei. In the solid state a distinction is made between three DNP enhancement mechanisms: the Solid Effect (SE), the Cross Effect (CE) and Thermal Mixing (TM). In an effort to determine the dominant DNP mechanisms responsible for the enhancement of the nuclear signals, electron and nuclear spin-lattice relaxation rates, enhancement buildup times and microwave (MW) swept DNP spectra were measured as a function of temperature and MW irradiation strength. We observed lineshape variations of the DNP spectra that indicated changes in the relative contributions of SE-DNP and CE-DNP with temperature and MW power. Using a theoretical model describing the SE-DNP and CE-DNP the DNP spectra could be analyzed without involving the TM-DNP mechanism and the relative SE-DNP and CE-DNP contributions to the nuclear enhancement could be determined. From this analysis it follows that lowering the temperature beyond 20 K increases the SE-DNP and decreases the CE-DNP contributions. Possible explanations for this behavior are suggested.

This article concerns the application of nuclear magnetic resonance (NMR) spectroscopic techniques to the analysis of geological materials and glasses. It includes inorganic minerals and glasses, but does not cover soils and clay minerals to any extent. The first part presents an overview of solid‐state NMR experiments applicable to inorganic solids. The range of nuclei accessible by NMR and the particular requirements for obtaining good spectra of more difficult nuclei, including quadrupolar nuclei, are discussed. The experimental conditions under which solid‐state NMR can provide quantitative analytical measurements are also considered.NMR spectroscopy provides element‐specific speciation and structural information including coordination environment and bond distances. It is particularly valuable for the analysis of amorphous and partially crystalline materials not amenable to structure determination by X‐ray diffraction. NMR can detect and quantify materials containing multiple phases and can be used for in situ monitoring of phase transitions. It provides qualitative and quantitative speciation information for framework nuclei in glasses and is also capable of characterizing the dynamic behavior of mobile ions and solvent through relaxation, diffusion and chemical exchange experiments. Thus it has become an important technique for the study of hydrous minerals and gels and for ion‐conducting glasses.The sensitivity of NMR varies considerably, depending on the nucleus observed, its abundance and its chemical environment. NMR sensitivities and detection limits cannot compete with elemental analytical techniques such as X‐ray fluorescence. In addition, quantitation in solids requires careful control of experimental parameters and careful calibration to avoid artifacts. However, the selectivity of NMR as an analytical technique is unsurpassed and the development of specialist pulse sequences to measure specific local interactions in solids makes it particularly well suited to the analysis of geological materials and glasses.NMR imaging enables structural information to be resolved in three dimensions, although resolution in solid‐state imaging is limited to tens of micrometers at best owing to the broader line widths and lower signal‐to‐noise ratios compared with liquids. However, capabilities in this field are being extended all the time and the application of NMR imaging techniques in materials analysis is expanding steadily. An alternative to conventional imaging is NMR force microscopy, which shows potential for surface mapping at higher resolutions.The applications section is organized on the basis of the materials being analyzed. Within each section, NMR techniques are classified according to the observed nuclei. The emphasis is on more recent applications and on developments leading to enhanced resolution and sensitivity. Silicates and aluminosilicates represent the largest class of applications, followed by phosphate, borate and other oxide glasses. Sol–gel materials and the reactions leading to gel formation are also discussed, as are hydrous materials more generally. The other important areas of application reviewed are minerals, ceramics, high‐temperature melts and ion‐conducting glasses. Finally, the applications of NMR imaging in this field, although sparse at present, are potentially very great. This is illustrated by two major areas of application to date, namely the imaging of bone minerals and cement and concrete.

Background In recent years, the focus of traditional Chinese medicine (TCM) research has gradually shifted from pure chemical research to looking at the combination of chemistry with the life sciences. However, due to the complexity of the chemical composition of Chinese medicinal plants, understanding material structure through in vivo and in vitro studies is a bottleneck in biological analysis. Nuclear magnetic resonance (NMR) spectroscopy has numerous unique advantages over other analytical techniques, and has developed into a crucial tool in Chinese medicine research. This review aims to analyze and summarize the application of NMR under the multiple fields of TCM. Methods The online databases PubMed, Web of Science, Embase, Cochrane Library, and CNKI were using the search terms “Nuclear magnetic resonance spectrometry,” “NMR,”“Chinese medicine,” “TCM,” “Herbal medicine,” were from January 1, 2010 to June 1, 2023 Results The research scopes were 375 after being selected. The latest applications of NMR to TCM including its application to metabolomics, structural identification and efficacy exploration, and authentication and quality control. There were 116 articles on metabolism, 196 articles on compound structure identification and 63 articles on quality control. The metabolomic study of NMR is in line with the multicomponent, multitarget, and overall comprehensive effect of TCM. The structural identification of the chemical components of TCM is more helpful for the discovery of other biologically active substances with high efficacy and few side effects. NMR provides support in quality control and planting site selection of TCM. Conclusion NMR has become an essential tool and makes great contributions to the field of TCM research, the innovation in the application of NMR technology will aid with the research on the material basis of TCM.

The complexity of the microstructure and fluids in unconventional reservoirs presents a significant challenge to the traditional approaches to the evaluation of geological formations and petrophysical properties due to the low porosity, ultralow permeability, complex lithology, and fluid composition. Nuclear magnetic resonance (NMR) techniques have been playing major roles in unconventional shale characterization in the last decades as NMR can provide critical information about the reservoirs for quantifying their petrophysical parameters and fluid properties and estimating productivity. Laboratory higher frequency (HF), e.g., 23-MHz NMR techniques, especially two-dimensional (2D) T1-T2 mapping, and applications have been essential for the noninvasive characterization of tight rock samples for identifying kerogen, bitumen, heavy or light hydrocarbons, and bound or capillary water. The traditional T2 cutoffs need new definitions to reflect the inferences from water and hydrocarbons separately. The legendary crushed rock analysis method, as applied to unconventional formations, has shown great success in evaluating total porosity and water saturation but suffers from inconsistency in results due to desiccation and solvent effects. The industry has witnessed significant development of HF-NMR techniques that couple advances in petrophysics, petroleum engineering, and geochemistry with a broad range of applications. This article will summarize key advances in laboratory NMR applications in unconventional shale characterization, including monitoring processes of liquids equilibrium, desiccation, and imbibition in fresh shale samples, determination of activation energy of hydrocarbons in shales, monitoring changes in a shale sample during liquid flooding experiment, and direct measurements on kerogen. Future NMR applications, such as in EOR, gas condensation, and saturation profile, will be discussed. In this article, we will review the following techniques: laboratory NMR, especially 23 MHz, techniques for unconventional shale sample measurements, 2D NMR T1-T2 mapping with an inter-echo spacing time of 0.7 ms at various sample temperatures, and early-time NMR signals acquired using the solid-echo pulse sequence together with pyrolysis results in kerogen studies. We will review the necessaries and advantages of the HF-NMR techniques and applications, explain the importance of the inter-echo spacing time in shale NMR experiments, give examples of monitoring liquid redistribution and desiccation in fresh shale samples, compare the results from NMR, Dean-Stark, and pyrolysis, examine the multidiscipline approaches as better tools to solve petrophysical problems. Examples include kerogen study using the solid-type NMR measurement combined with geochemical pyrolysis and NMR combined with capillary pressure. There has been significant advancement of NMR techniques in unconventional shale evaluation over the last decade. It is time for us to summarize such technological advances and draw conclusions to help us in planning unconventional core analysis programs.

Solid-state MAS NMR at ultra low temperature of hydrated alanine doped with DNP radicals

Paramagnet induced signal quenching in MAS–DNP experiments in frozen homogeneous solutions