Category Archives: Review

Polarizing Agents: Evolution and Outlook in Free Radical Development for DNP #DNPNMR

Casano, Gilles, Hakim Karoui, and Olivier Ouari. “Polarizing Agents: Evolution and Outlook in Free Radical Development for DNP” 7 (2018): 14.

https://doi.org/10.1002/9780470034590.emrstm1547.

In this article, we describe an in-depth overview of the development of paramagnetic polarizing agents for dynamic nuclear polarization (DNP)-enhanced solid-state magic angle spinning (MAS) nuclear magnetic resonance (NMR). In DNP experiments, the large polarization of unpaired electrons is transferred to surrounding nuclei, which provides a maximum theoretical DNP enhancement of 660 for 1H NMR. The article includes a description of the different polarizing mechanisms and outlines key structural and magnetic parameters that contributed to the rational design of improved polarizing sources. The application of (di)nitroxides, heterobiradicals, narrow-line radicals, paramagnetic metal ions as well as site-specific polarizing agents is discussed. With the best polarizing agents, ssNMR MAS NMR/DNP enhances sensitivity by a factor of up to 200, providing decreased experiment time by five orders of magnitude and opening new avenues for NMR.

Millimeter-wave Sources for DNP-NMR #DNPNMR

Blank, Monica, and Kevin L Felch. “Millimeter-Wave Sources for DNP-NMR” 7 (2018): 12.

https://doi.org/10.1002/9780470034590.emrstm1582

Advances in both solid-state and vacuum-electron-based sources at frequencies greater than 200 GHz have been a key factor in the recent improvements in solid-state dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) instrumentation. The current state of the art in solid-state sources and vacuum-electron devices (VEDs), such as extended interaction oscillators (EIOs), extended interaction klystrons (EIKs), and gyrotrons for DNP applications are described. The key features and design aspects of gyrotrons, which are presently the most promising DNP sources for high-field NMR systems, are detailed. In addition, the current capabilities of high-performance DNP gyrotron sources are illustrated. The status of ongoing research efforts in DNP gyrotrons and future directions are discussed.

DNP in Materials Science: Touching the Surface #DNPNMR

Berruyer, Pierrick, Lyndon Emsley, and Anne Lesage. “DNP in Materials Science: Touching the Surface,” 7:12, 2018.

https://doi.org/10.1002/9780470034590.emrstm1554.

Dynamic nuclear polarization (DNP)-enhanced solid-state NMR spectroscopy under magic-angle spinning has recently emerged as a unique analytical method to probe surfaces at atomic resolution. In this article, we first describe the basic principles of dynamic nuclear polarization surface enhanced NMR spectroscopy (DNP SENS). The article continues with a large review of recent literature that illustrates the versatility of this technique and its incredible potential to reveal new structural features at surfaces with details at an unprecedented level. The most recent developments, such as the application of DNP SENS to highly reactive surface sites, are finally covered.

Relaxation Mechanisms #DNPNMR #EPR

This is an excellent review and summary on different relaxation mechanisms observed in EPR spectroscopy. Understanding EPR relaxation is crucial to understand the DNP process.

Eaton, Sandra S., and Gareth R. Eaton. “Relaxation Mechanisms.” In EMagRes, edited by Robin K. Harris and Roderick L. Wasylishen, 1543–56. Chichester, UK: John Wiley & Sons, Ltd, 2016.

https://doi.org/10.1002/9780470034590.emrstm1507

After a paramagnetic species absorbs energy, there are various relaxation processes by which the excitation energy is lost to the surroundings thereby enabling return to the ground state. The focus of this article is on relaxation of species with S= 1∕2 in magnetically dilute samples. The relative importance of various spin–lattice relaxation processes for each paramagnetic species is strongly dependent on temperature, electronic, and molecular structure. The Raman and local-mode processes make significant contributions to T 1 relaxation in rigid and semirigid lattices for a wide range of species at temperature above about 10 K. The Orbach process requires a low-lying excited state. The thermally activated process is significant when a stochastic process averages inequivalent environments on a timescale comparable to the Larmor frequency, as occurs by rotation of methyl groups or hopping of a hydrogen-bonded proton. Spin-echo dephasing at low temperatures is dominated by nuclear spin diffusion. It is enhanced by dynamic processes that average inequivalently coupled nuclei on the time scale of the hyperfine interaction and by motions that average g and A anisotropy. Analysis of the processes that contribute to relaxation as a function of temperature is shown for triarylmethyl radicals, semiquinones, nitroxides, Cu2+ complexes, iron–sulfur complexes, and radicals in irradiated solids. In fluid solution, motion provides additional relaxation mechanisms. Analysis of T2 in solution is a powerful tool to elucidate motion. Experiments as a function of both temperature and resonance frequency are key to distinguishing between relaxation mechanisms.

NMR-based metabolomics and fluxomics: developments and future prospects #DNPNMR

Giraudeau, Patrick. “NMR-Based Metabolomics and Fluxomics: Developments and Future Prospects.” The Analyst 145, no. 7 (2020): 2457–72.

https://doi.org/10.1039/D0AN00142B.

NMR spectroscopy is an essential analytical technique in metabolomics and fluxomics workflows, owing to its high structural elucidation capabilities combined with its intrinsic quantitative nature. However, routine NMR “omic” analytical methods suffer from several drawbacks that may have limited their use as a method of choice, in particular when compared to another widely used technique, mass spectrometry. This review describes, in a critical and perspective discussion, how some of the most recent developments emerging from the NMR community could act as real game changers for metabolomics and fluxomics in the near future. Advanced developments to make NMR metabolomics more resolutive, more sensitive and more accessible are described, as well as new approaches to improve the identification of biomarkers. We hope that this review will convince a broad end-user community of the increasing role of NMR in the “omic” world at the beginning of the 2020s.

DNP Solid-state NMR of Biological Membranes #DNPNMR

Bechinger, Burkhard. “DNP Solid-State NMR of Biological Membranes” 7 (2018): 10. 

https://doi.org/10.1002/9780470034590.emrstm1558.

While solid-state NMR/DNP has become a well-established technique to significantly increase the signals of molecules embedded in homogeneous glassy matrices, the enhancement factors observed in heterogeneous and/or matrix-free samples lag somewhat behind. The possible reasons for such differences, present limitations, and future prospects of solid-state NMR/DNP are discussed in the context of membrane protein investigations. Membrane polypeptides and lipids are studied by MAS as well as oriented sample solid-state NMR approaches. Notably, even the more modest DNP signal enhancements obtained in such samples augment the signal intensities by 1–2 orders of magnitude, thus opening up new territory in structural biology by allowing the detection of new conformers, so far invisible intermediate states, or the acquisition of smaller quantities of membrane-associated polypeptides in much less time. New sample preparation protocols, dedicated instrumental hardware, and specifically designed biradicals have much improved the application of DNP to membranes using MAS and/or oriented solid-state NMR technologies.

In Vivo Hyperpolarized 13C MRS and MRI Applications #DNPNMR

Marco-Rius, Irene, and Arnaud Comment. “In Vivo Hyperpolarized 13C MRS and MRI Applications,” 7:12, 2018.

https://doi.org/10.1002/9780470034590.emrstm1592

The tremendous polarization enhancement afforded by dissolution dynamic nuclear polarization (DNP) can be taken advantage of to perform molecular and metabolic imaging. Following the injection of molecules that are hyperpolarized via dissolution DNP, real-time measurements of their biodistribution and metabolic conversion can be recorded. This technology therefore provides a unique and invaluable tool for probing cellular metabolism in vivo in a noninvasive manner. It gives the opportunity to follow and evaluate disease progression and treatment response without requiring ex vivo destructive tissue assays. Seven sites across the globe are currently performing human studies using hyperpolarized 13C-pyruvate, and several other institutions are on the brink of being ready to inject their first patients. The most promising fields of application of this technology are in oncology and cardiology, and the aim of this article is to provide an overview of some of the current in vivo preclinical and clinical applications of hyperpolarized 13C magnetic resonance spectroscopy and imaging. Some new approaches and potential future developments to improve the hyperpolarized 13C technology are also presented and discussed.

DNP NMR of biomolecular assemblies #DNPNMR

Jaudzems, Kristaps, Tatyana Polenova, Guido Pintacuda, Hartmut Oschkinat, and Anne Lesage. “DNP NMR of Biomolecular Assemblies.” Journal of Structural Biology 206, no. 1 (April 2019): 90–98.

https://doi.org/10.1016/j.jsb.2018.09.011

Dynamic Nuclear Polarization (DNP) is an effective approach to alleviate the inherently low sensitivity of solid-state NMR (ssNMR) under magic angle spinning (MAS) towards large-sized multi-domain complexes and assemblies. DNP relies on a polarization transfer at cryogenic temperatures from unpaired electrons to adjacent nuclei upon continuous microwave irradiation. This is usually made possible via the addition in the sample of a polarizing agent. The first pioneering experiments on biomolecular assemblies were reported in the early 2000s on bacteriophages and membrane proteins. Since then, DNP has experienced tremendous advances, with the development of extremely efficient polarizing agents or with the introduction of new microwaves sources, suitable for NMR experiments at very high magnetic fields (currently up to 900 MHz). After a brief introduction, several experimental aspects of DNP enhanced NMR spectroscopy applied to biomolecular assemblies are discussed. Recent demonstration experiments of the method on viral capsids, the type III and IV bacterial secretion systems, ribosome and membrane proteins are then described.

DNP NMR of biomolecular assemblies #DNPNMR

Jaudzems, Kristaps, Tatyana Polenova, Guido Pintacuda, Hartmut Oschkinat, and Anne Lesage. “DNP NMR of Biomolecular Assemblies.” Journal of Structural Biology 206, no. 1 (April 2019): 90–98.

https://doi.org/10.1016/j.jsb.2018.09.011.

Dynamic Nuclear Polarization (DNP) is an effective approach to alleviate the inherently low sensitivity of solid-state NMR (ssNMR) under magic angle spinning (MAS) towards large-sized multi-domain complexes and assemblies. DNP relies on a polarization transfer at cryogenic temperatures from unpaired electrons to adjacent nuclei upon continuous microwave irradiation. This is usually made possible via the addition in the sample of a polarizing agent. The first pioneering experiments on biomolecular assemblies were reported in the early 2000s on bacteriophages and membrane proteins. Since then, DNP has experienced tremendous advances, with the development of extremely efficient polarizing agents or with the introduction of new microwaves sources, suitable for NMR experiments at very high magnetic fields (currently up to 900 MHz). After a brief introduction, several experimental aspects of DNP enhanced NMR spectroscopy applied to biomolecular assemblies are discussed. Recent demonstration experiments of the method on viral capsids, the type III and IV bacterial secretion systems, ribosome and membrane proteins are then described.

Progress in low-field benchtop NMR spectroscopy in chemical and biochemical analysis

Grootveld, Martin, Benita Percival, Miles Gibson, Yasan Osman, Mark Edgar, Marco Molinari, Melissa L. Mather, Federico Casanova, and Philippe B. Wilson. “Progress in Low-Field Benchtop NMR Spectroscopy in Chemical and Biochemical Analysis.” Analytica Chimica Acta 1067 (August 2019): 11–30.

https://doi.org/10.1016/j.aca.2019.02.026

The employment of spectroscopically-resolved NMR techniques as analytical probes have previously been both prohibitively expensive and logistically challenging in view of the large sizes of high-field facilities. However, with recent advances in the miniaturisation of magnetic resonance technology, low-field, cryogen-free “benchtop” NMR instruments are seeing wider use. Indeed, these miniaturised spectrometers are utilised in areas ranging from food and agricultural analyses, through to human biofluid assays and disease monitoring. Therefore, it is both intrinsically timely and important to highlight current applications of this analytical strategy, and also provide an outlook for the future, where this approach may be applied to a wider range of analytical problems, both qualitatively and quantitatively. © 2019 Elsevier B.V. All rights reserved.

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