Progress in Nuclear Magnetic Resonance Spectroscopy最新文献

Among current modalities of biomedical and diagnostic imaging, MRI stands out by virtue of its versatile contrast obtained without ionizing radiation. However, in various cases, e.g., water protons in tissues such as bone, tendon, and lung, MRI performance is limited by the rapid decay of resonance signals associated with short transverse relaxation times T₂ or T₂*. Efforts to address this shortcoming have led to a variety of specialized short-T₂ techniques. Recent progress in this field expands the choice of methods and prompts fresh considerations with regard to instrumentation, data acquisition, and signal processing. In this review, the current status of short-T₂ MRI is surveyed. In an attempt to structure the growing range of techniques, the presentation highlights overarching concepts and basic methodological options. The most frequently used approaches are described in detail, including acquisition strategies, image reconstruction, hardware requirements, means of introducing contrast, sources of artifacts, limitations, and applications.

In this review, we present the physical principles of the SABRE (Signal Amplification By Reversible Exchange) method. SABRE is a promising hyperpolarization technique that enhances NMR signals by transferring spin order from parahydrogen (an isomer of the H₂ molecule that is in a singlet nuclear spin state) to a substrate that is to be polarized. Spin order transfer takes place in a transient organometallic complex which binds both parahydrogen and substrate molecules; after dissociation of the SABRE complex, free hyperpolarized substrate molecules are accumulated in solution. An advantage of this method is that the substrate is not modified chemically, and its polarization can be regenerated multiple times by bubbling fresh parahydrogen through the solution. Thus, SABRE requires two key ingredients: (i) polarization transfer and (ii) chemical exchange of both parahydrogen and substrate. While there are several excellent reviews on applications of SABRE, the background of the method is discussed less frequently. In this review we aim to explain in detail how SABRE hyperpolarization is formed, focusing on key aspects of both spin dynamics and chemical kinetics, as well as on the interplay between them. Hence, we first cover the known spin order transfer methods applicable to SABRE — cross-relaxation, coherent spin mixing at avoided level crossings, and coherence transfer — and discuss their practical implementation for obtaining SABRE polarization in the most efficient way. Second, we introduce and explain the principle of SABRE hyperpolarization techniques that operate at ultralow (<1 μT), at low (1μT to 0.1 T) and at high (>0.1 T) magnetic fields. Finally, chemical aspects of SABRE are discussed in detail, including chemical systems that are amenable to SABRE and the exchange processes that are required for polarization formation. A theoretical treatment of the spin dynamics and their interplay with chemical kinetics is also presented. This review outlines known aspects of SABRE and provides guidelines for the design of new SABRE experiments, with the goal of solving practical problems of enhancing weak NMR signals.

Whereas high resolution NMR at temperatures up to 550 K can be routinely performed selecting from a variety of commercially available NMR hardware, experiments in the high temperature regime, defined here as T > 550 K, have been restricted to just a few specialized laboratories. In this contribution we present important developments of high temperature NMR over the last decades. Various methods to achieve high resolution high temperature NMR, including resistive heating, laser-assisted heating and inductive heating, are presented and their specific advantages and disadvantages discussed. The various ways of temperature monitoring including the use of chemical shift thermometers or T₁ thermometers are reviewed. In the last section, some typical application examples from the field of oxidic glasses and melts are given.

The properties of the LASER with respect to self-organization are compared with the key features of the p-H₂ pumped RASER. According to LASER theory the equations of motion for the LASER can be derived from the enslaving principle, i.e. the slowest-changing order parameter (the light field in the resonator) enslaves the rapidly relaxing atomic degrees of freedom. Likewise, it is shown here that the equations of motion for the p-H₂ pumped RASER result from a set of order parameters, where the transverse magnetization of the RASER-active spin states enslaves the electromagnetic modes. The consequences are striking for nuclear magnetic resonance (NMR) spectroscopy, since long-lasting multi-mode RASER oscillations enable unprecedented spectroscopic resolution down to the micro-Hertz regime. Based on the theory for multi-mode RASER operation we analyze the conditions that reveal either the collapse of the entire NMR spectrum, the occurrence of self-organized frequency-combs, or RASER spectra which reflect the J-coupled network of the molecule. Certain RASER experiments involving the protons of ¹⁵N pyridine or 3-picoline molecules pumped with p-H₂ via SABRE (Signal Amplification By Reversible Exchange) show either a single RASER oscillation in the time domain, giant RASER pulses or a complex RASER beat pattern. The corresponding ¹H spectra consist of one narrow line, equidistant narrow lines (frequency-comb), or highly resolved lines reporting NMR properties, respectively. Numerous applications in the areas of material sciences, fundamental physics and medicine involving high precision sensors for magnetic fields, rotational motions or molecular structures become feasible.

This review describes the latest developments in the field of ¹⁷O NMR spectroscopy of organic and biological molecules both in aqueous solution and in the solid state. In the first part of the review, a general theoretical description of the nuclear quadrupole relaxation process in isotropic liquids is presented at a mathematical level suitable for non-specialists. In addition to the first-order quadrupole interaction, the theory also includes additional relaxation mechanisms such as the second-order quadrupole interaction and its cross correlation with shielding anisotropy. This complete theoretical treatment allows one to assess the transverse relaxation rate (thus the line width) of NMR signals from half-integer quadrupolar nuclei in solution over the entire range of motion. On the basis of this theoretical framework, we discuss general features of quadrupole-central-transition (QCT) NMR, which is a particularly powerful method of studying biomolecules in the slow motion regime. Then we review recent advances in ¹⁷O QCT NMR studies of biological macromolecules in aqueous solution. The second part of the review is concerned with solid-state ¹⁷O NMR studies of organic and biological molecules. As a sequel to the previous review on the same subject [G. Wu, Prog. Nucl. Magn. Reson. Spectrosc. 52 (2008) 118–169], the current review provides a complete coverage of the literature published since 2008 in this area.

Membrane proteins are important players in signal transduction and the exchange of metabolites within or between cells. Thus, this protein class is the target of around 60 % of currently marketed drugs, emphasizing their essential biological role. Besides functional assays, structural and dynamical investigations on this protein class are crucial to fully understanding their functionality. Even though X-ray crystallography and electron microscopy are the main methods to determine structures of membrane proteins and their complexes, NMR spectroscopy can contribute essential information on systems that (a) do not crystallize and (b) are too small for EM. Furthermore, NMR is a versatile tool for monitoring functional dynamics of biomolecules at various time scales. A crucial aspect of such studies is the use of a membrane mimetic that resembles a native environment and thus enables the extraction of functional insights. In recent decades, the membrane protein NMR community has moved from rather harsh detergents to membrane systems having more native-like properties. In particular, most recently phospholipid nanodiscs have been developed and optimized mainly for solution-state NMR but are now also being used for solid-state NMR spectroscopy. Nanodiscs consist of a patch of a planar lipid bilayer that is encircled by different (bio-)polymers to form particles of defined and tunable size. In this review, we provide an overview of available membrane mimetics, including nanodiscs, amphipols and bicelles, that are suitable for high-resolution NMR spectroscopy and describe how these advanced membrane mimetics can facilitate NMR studies on the structure and dynamics of membrane proteins. Since the stability of membrane proteins depends critically on the chosen membrane mimetic, we emphasize the importance of a suitable system that is not necessarily developed for solution-state NMR applications and hence requires optimization for each membrane protein. However, lipid-based membrane mimetics offer the possibility of performing NMR experiments at elevated temperatures and studying ligand and partner protein complexes as well as their functional dynamics in a realistic membrane environment. In order to be able to make an informed decision during the selection of a suitable membrane system, we provide a detailed overview of the available options for various membrane protein classes and thereby facilitate this often-difficult selection process for a broad range of desired NMR applications.

In this review, lanthanide chelating tags and their applications to pseudocontact shift NMR spectroscopy as well as analysis of residual dipolar couplings are covered. A complete overview is presented of DOTA-derived and non-DOTA-derived lanthanide chelating tags, critical points in the design of lanthanide chelating tags as appropriate linker moieties, their stability under reductive conditions, e.g., for in-cell applications, the magnitude of the anisotropy transferred from the lanthanide chelating tag to the biomacromolecule under investigation and structural properties, as well as conformational bias of the lanthanide chelating tags are discussed. Furthermore, all DOTA-derived lanthanide chelating tags used for PCS NMR spectroscopy published to date are displayed in tabular form, including their anisotropy parameters, with all employed lanthanide ions, C_B-Ln distances and tagging reaction conditions, i.e., the stoichiometry of lanthanide chelating tags, pH, buffer composition, temperature and reaction time. Additionally, applications of lanthanide chelating tags for pseudocontact shifts and residual dipolar couplings that have been reported for proteins, protein-protein and protein-ligand complexes, carbohydrates, carbohydrate-protein complexes, nucleic acids and nucleic acid-protein complexes are presented and critically reviewed. The vast and impressive range of applications of lanthanide chelating tags to structural investigations of biomacromolecules in solution clearly illustrates the significance of this particular field of research. The extension of the repertoire of lanthanide chelating tags from proteins to nucleic acids holds great promise for the determination of valuable structural parameters and further developments in characterizing intermolecular interactions.

The magnetic interactions between the nuclear magnetic moment and the magnetic moment of unpaired electron(s) depend on the structure and dynamics of the molecules where the paramagnetic center is located and of their partners. The long-range nature of the magnetic interactions is thus a reporter of invaluable information for structural biology studies, when other techniques often do not provide enough data for the atomic-level characterization of the system. This precious information explains the flourishing of paramagnetism-assisted NMR studies in recent years. Many paramagnetic effects are related to the magnetic susceptibility of the paramagnetic metal. Although these effects have been known for more than half a century, different theoretical models and new approaches have been proposed in the last decade. In this review, we have summarized the consequences for NMR spectroscopy of magnetic interactions between nuclear and electron magnetic moments, and thus of the presence of a magnetic susceptibility due to metals, and we do so using a unified notation.

Magic-angle spinning (MAS) solid-state NMR has provided structural insights into various bacteriophage systems including filamentous, spherical, and tailed bacteriophage viruses. A variety of methodologies have been utilized including elementary two and three-dimensional assignment experiments, proton-detection techniques at fast spinning speeds, non-uniform sampling, structure determination protocols, conformational dynamics revealed by recoupling of anisotropic interactions, and enhancement by dynamic nuclear polarization. This review summarizes most of the studies performed during the last decade by MAS techniques and makes comparisons with prior knowledge obtained from static and solution NMR techniques. Chemical shifts for the capsids of the various systems are reported and analyzed, and DNA shifts are reported and discussed in the context of general high molecular-weight DNA molecules. Chemical shift and torsion angle prediction techniques are compared and applied to the various phage systems. The structures of the intact M13 filamentous bacteriophage and that of the Acinetobacter phage AP205 capsid, determined using MAS-based experimental data, are presented. Finally, filamentous phages, which are highly rigid systems, show interesting dynamics at the interface of the capsid and DNA, and their mutual electrostatic interactions are shown to be mediated by highly mobile positively charged residues. Novel results obtained from recoupling the chemical shift anisotropy of a single arginine in IKe phage, which is in contact with its DNA, further demonstrate this point. MAS NMR thus provides many new insights into phage structure, and on the other hand the richness, complexity and variety of bacteriophage systems provide opportunities for new NMR methodologies and technique developments.