Progress in Nuclear Magnetic Resonance Spectroscopy最新文献

Amyloid fibrils are insoluble, fibrous nanostructures that accumulate extracellularly in biological tissue during the progression of several human disorders, including Alzheimer’s disease (AD) and type 2 diabetes. Fibrils are assembled from protein monomers via the transient formation of soluble, cytotoxic oligomers, and have a common molecular architecture consisting of a spinal core of hydrogen-bonded protein β-strands. For the past 25 years, NMR spectroscopy has been at the forefront of research into the structure and assembly mechanisms of amyloid aggregates. Until the recent boom in fibril structure analysis by cryo-electron microscopy, solid-state NMR was unrivalled in its ability to provide atomic-level models of amyloid fibril architecture. Solution-state NMR has also provided complementary information on the early stages in the amyloid assembly mechanism. Now, both NMR modalities are proving to be valuable in unravelling the complex interactions between amyloid species and a diverse range of physiological metal ions, molecules and surfaces that influence the assembly pathway, kinetics, morphology and clearance in vivo. Here, an overview is presented of the main applications of solid-state and solution-state NMR for studying the interactions between amyloid proteins and biomembranes, glycosaminoglycan polysaccharides, metal ions, polyphenols, synthetic therapeutics and diagnostics. Key NMR methodology is reviewed along with examples of how to overcome the challenges of detecting interactions with aggregating proteins. The review heralds this new role for NMR in providing a comprehensive and pathologically-relevant view of the interactions between protein and non-protein components of amyloid. Coverage of both solid- and solution-state NMR methods and applications herein will be informative and valuable to the broad communities that are interested in amyloid proteins.

We describe the utility of small nutation angle (acute; <90°) ¹H radiofrequency pulses for efficient manipulation of magnetization in selectively [¹³CH₃]-labeled methyl groups of otherwise deuterated proteins. Focusing primarily on NMR applications that target either fast (pico-to-nanosecond) motions of the methyl group three-fold rotation axis, or slow (micro-to-millisecond) processes associated with chemical exchange, we show that significant simplification of the ¹³CH₃ spin-system and, as a consequence, of NMR pulse schemes, may be achieved in certain cases by the proper choice of the flip-angle of the ¹H acute-angle pulse. In other instances, appropriate adjustment of acute-angle ¹H pulses permits optimization of the sensitivity of NMR experiments. The results of acute-angle pulse based NMR experiments are validated by comparison with well-established NMR techniques for the characterization of fast dynamics of methyl-containing side-chains and chemical exchange processes.

In recent years, there has been remarkable progress in the field of dissolution dynamic nuclear polarization (D-DNP). This method has shown significant potential for enhancing nuclear polarization by over 10,000 times, resulting in a substantial increase in sensitivity. The unprecedented signal enhancements achieved with D-DNP have opened new possibilities for in vitro analysis. This method enables the monitoring of structural and enzymatic kinetics with excellent time resolution at low concentrations. Furthermore, these advances can be straightforwardly translated to in vivo magnetic resonance imaging and magnetic resonance spectroscopy (MRI and MRS) experiments. D-DNP studies have used a range of ¹³C labeled molecules to gain deeper insights into the cellular metabolic pathways and disease hallmarks. Over the last 15 years, D-DNP has been used to analyze glutamine, a key player in the cellular metabolism, involved in many diseases including cancer. Glutamine is the most abundant amino acid in blood plasma and the major carrier of nitrogen, and it is converted to glutamate inside the cell, where the latter is the most abundant amino acid. It has been shown that increased glutamine consumption by cells is a hallmark of tumor cancer metabolism. In this review, we first highlight the significance of glutamine in metabolism, providing an in-depth description of its use at the cellular level as well as its specific roles in various organs. Next, we present a comprehensive overview of the principles of D-DNP. Finally, we review the state of the art in D-DNP glutamine analysis and its application in oncology, neurology, and perfusion marker studies.

Magnetic resonance elastography (MRE) is an emerging clinical imaging modality for characterizing the viscoelastic properties of soft biological tissues. MRE shows great promise in the noninvasive diagnosis of various diseases, especially those associated with soft tissue changes involving the extracellular matrix, cell density, or fluid turnover including altered blood perfusion – all hallmarks of inflammation from early events to cancer development. This review covers the fundamental principles of measuring tissue viscoelasticity by MRE, which are based on the stimulation and encoding of shear waves and their conversion into parameter maps of mechanical properties by inverse problem solutions of the wave equation. Technical challenges posed by real-world biological tissue properties such as viscosity, heterogeneity, anisotropy, and nonlinear elastic behavior of tissues are discussed. Applications of MRE measurement in both humans and animal models are presented, with emphasis on the detection, characterization, and staging of diseases related to the cascade of biomechanical property changes from early to chronic inflammation in the liver and brain. Overall, MRE provides valuable insights into the biophysics of soft tissues for imaging-based detection and staging of inflammation-associated tissue changes.

Dynamic nuclear polarization (DNP) is a method for achieving high levels of nuclear spin polarization by transferring spin polarization from electrons to nuclei by microwave irradiation, resulting in higher sensitivity in NMR/MRI. In particular, DNP using photoexcited triplet electron spins (triplet-DNP) can provide a hyperpolarized nuclear spin state at room temperature and in low magnetic field. In this review article, we highlight recent developments in materials and instrumentation for the application of triplet-DNP. First, a brief history and principles of triplet-DNP will be presented. Next, important advances in recent years will be outlined: new materials to hyperpolarize water and biomolecules; high-sensitivity solution NMR by dissolution triplet-DNP; and strategies for further improvement of the polarization. In view of these developments, future directions to widen the range of applications of triplet-DNP will be discussed.

This review focuses on the application of nuclear magnetic resonance (NMR) spectroscopy in the study of lithium and sodium battery electrolytes. Lithium-ion batteries are widely used in electronic devices, electric vehicles, and renewable energy systems due to their high energy density, long cycle life, and low self-discharge rate. The sodium analog is still in the research phase, but has significant potential for future development. In both cases, the electrolyte plays a critical role in the performance and safety of these batteries. NMR spectroscopy provides a non-invasive and non-destructive method for investigating the structure, dynamics, and interactions of the electrolyte components, including the salts, solvents, and additives, at the molecular level. This work attempts to give a nearly comprehensive overview of the ways that NMR spectroscopy, both liquid and solid state, has been used in past and present studies of various electrolyte systems, including liquid, gel, and solid-state electrolytes, and highlights the insights gained from these studies into the fundamental mechanisms of ion transport, electrolyte stability, and electrode-electrolyte interfaces, including interphase formation and surface microstructure growth. Overviews of the NMR methods used and of the materials covered are presented in the first two chapters. The rest of the review is divided into chapters based on the types of electrolyte materials studied, and discusses representative examples of the types of insights that NMR can provide.

Nuclear magnetic resonance is arguably both the best available quantum technology for implementing simple quantum computing experiments and the worst technology for building large scale quantum computers that has ever been seriously put forward. After a few years of rapid growth, leading to an implementation of Shor’s quantum factoring algorithm in a seven-spin system, the field started to reach its natural limits and further progress became challenging. Rather than pursuing more complex algorithms on larger systems, interest has now largely moved into developing techniques for the precise and efficient manipulation of spin states with the aim of developing methods that can be applied in other more scalable technologies and within conventional NMR. However, the user friendliness of NMR implementations means that they remain popular for proof-of-principle demonstrations of simple quantum information protocols.

Most proteins perform their functions in crowded and complex cellular environments where weak interactions are ubiquitous between biomolecules. These complex environments can modulate the protein folding energy landscape and hence affect protein stability. NMR is a nondestructive and effective method to quantify the kinetics and equilibrium thermodynamic stability of proteins at an atomic level within crowded environments and living cells. Here, we review NMR methods that can be used to measure protein stability, as well as findings of studies on protein stability in crowded environments mimicked by polymer and protein crowders and in living cells. The important effects of chemical interactions on protein stability are highlighted and compared to spatial excluded volume effects.