Progress in Nuclear Magnetic Resonance Spectroscopy最新文献

It has always been of considerable interest to study the nuclear magnetic resonance response of multiple nuclei simultaneously, whether these signals arise from internuclear couplings within the same molecule, or from uncoupled nuclei within sample mixtures. The literature contains numerous uncorrelated reports on techniques employed to achieve multi-nuclear NMR detection. This paper consolidates the subset of techniques in which single coil detectors are utilized, and highlights the strengths and weaknesses of each approach, at the same time pointing the way towards future developments in the field of multi-nuclear NMR. We compare the different multi-nuclear NMR techniques in terms of performance, and present a guide to NMR probe designers towards application-based optimum design. We also review the applicability of micro-coils in the context of multi-nuclear methods. Micro-coils benefit from compact geometries and exhibit lower impedance, which provide new opportunities and challenges for the NMR probe designer.

This review describes off-resonance R_1ρ relaxation dispersion NMR methods for characterizing microsecond-to-millisecond chemical exchange in uniformly ¹³C/¹⁵N labeled nucleic acids in solution. The review opens with a historical account of key developments that formed the basis for modern R_1ρ techniques used to study chemical exchange in biomolecules. A vector model is then used to describe the R_1ρ relaxation dispersion experiment, and how the exchange contribution to relaxation varies with the amplitude and frequency offset of an applied spin-locking field, as well as the population, exchange rate, and differences in chemical shifts of two exchanging species. Mathematical treatment of chemical exchange based on the Bloch-McConnell equations is then presented and used to examine relaxation dispersion profiles for more complex exchange scenarios including three-state exchange. Pulse sequences that employ selective Hartmann-Hahn cross-polarization transfers to excite individual ¹³C or ¹⁵N spins are then described for measuring off-resonance R_1ρ(¹³C) and R_1ρ(¹⁵N) in uniformly ¹³C/¹⁵N labeled DNA and RNA samples prepared using commercially available ¹³C/¹⁵N labeled nucleotide triphosphates. Approaches for analyzing R_1ρ data measured at a single static magnetic field to extract a full set of exchange parameters are then presented that rely on numerical integration of the Bloch-McConnell equations or the use of algebraic expressions. Methods for determining structures of nucleic acid excited states are then reviewed that rely on mutations and chemical modifications to bias conformational equilibria, as well as structure-based approaches to calculate chemical shifts. Applications of the methodology to the study of DNA and RNA conformational dynamics are reviewed and the biological significance of the exchange processes is briefly discussed.

The most recent results dealing with the computation of ¹³C NMR chemical shifts in chemistry (small molecules, saturated, unsaturated and aromatic compounds, heterocycles, functional derivatives, coordination complexes, carbocations, and natural products) are reviewed, paying special attention to theoretical background and accuracy, the latter involving solvent effects, vibrational corrections, and relativistic effects.

Over the past two decades, diffusion MRI has become an essential tool in neuroimaging investigations. This is due to its sensitivity to the motion of water molecules as they diffuse through the microstructural environment, allowing diffusion MRI to be used as a ‘probe’ of tissue microstructure. Furthermore, this sensitivity is strongly direction-dependent, notably in brain white matter, due to the alignment of structures that restrict or hinder the motion of water molecules, notably axonal membranes. This provides a means of inferring the orientation of fibres in vivo, and by use of appropriate fibre-tracking algorithms, of delineating the path of white matter tracts in the brain. The ability to perform so-called tractography in humans in vivo non-invasively is unique to diffusion MRI, and is now used in applications such as neurosurgery planning and more broadly within investigations of brain connectomics. This review describes the theory and concepts of diffusion MRI and describes its most important areas of application in the brain, with a strong focus on tractography.

Unconventional shale reservoirs have greatly contributed to the recent surge in petroleum production in the United States and are expected to lead the US oil production to a historical high in 2018. The complexity of the rocks and fluids in these reservoirs presents a significant challenge to the traditional approaches to the evaluation of geological formations due to the low porosity, permeability, complex lithology and fluid composition. NMR has emerged as the key measurement for evaluating these reservoirs, for quantifying their petrophysical parameters, fluid properties, and determining productivity. Measurement of the $T_1/T_2$ ratio by 2D NMR has been found to be critical for identifying the fluid composition of kerogen, bitumen, light/heavy oils, gases and brine in these formations. This paper will first provide a brief review of the theories of relaxation, measurement methods, and data inversion techniques and then will discuss several examples of applications of these NMR methods for understanding various aspects of the unconventional reservoirs. At the end, we will briefly discuss a few other topics, which are still in their developmental stages, such as solid state NMR, and their potential applications for shale rock evaluation.

The field of paramagnetic NMR has expanded considerably in recent years. This review addresses both the theoretical description of paramagnetic NMR, and the way in which it is currently practised. We provide a review of the theory of the NMR parameters of systems in both solution and the solid state. Here we unify the different languages used by the NMR, EPR, quantum chemistry/DFT, and magnetism communities to provide a comprehensive and coherent theoretical description. We cover the theory of the paramagnetic shift and shift anisotropy in solution both in the traditional formalism in terms of the magnetic susceptibility tensor, and using a more modern formalism employing the relevant EPR parameters, such as are used in first-principles calculations. In addition we examine the theory first in the simple non-relativistic picture, and then in the presence of spin-orbit coupling. These ideas are then extended to a description of the paramagnetic shift in periodic solids, where it is necessary to include the bulk magnetic properties, such as magnetic ordering at low temperatures. The description of the paramagnetic shift is completed by describing the current understanding of such shifts due to lanthanide and actinide ions. We then examine the paramagnetic relaxation enhancement, using a simple model employing a phenomenological picture of the electronic relaxation, and again using a more complex state-of-the-art theory which incorporates electronic relaxation explicitly. An additional important consideration in the solid state is the impact of bulk magnetic susceptibility effects on the form of the spectrum, where we include some ideas from the field of classical electrodynamics. We then continue by describing in detail the solution and solid-state NMR methods that have been deployed in the study of paramagnetic systems in chemistry, biology, and the materials sciences. Finally we describe a number of case studies in paramagnetic NMR that have been specifically chosen to highlight how the theory in part one, and the methods in part two, can be used in practice. The systems chosen include small organometallic complexes in solution, solid battery electrode materials, metalloproteins in both solution and the solid state, systems containing lanthanide ions, and multi-component materials used in pharmaceutical controlled-release formulations that have been doped with paramagnetic species to measure the component domain sizes.

Preparation of a protein sample for solid-state NMR is in many aspects similar to solution-state NMR approaches, mainly with respect to the need for stable isotope labeling. But the possibility of using solid-state NMR to investigate membrane proteins in (native) lipids adds the important requirement of adapted membrane-reconstitution schemes. Also, dynamic nuclear polarization and paramagnetic NMR in solids need specific schemes using metal ions and radicals. Sample sedimentation has enabled structural investigations of objects inaccessible to other structural techniques, but rotor filling using sedimentation has become increasingly complex with smaller and smaller rotors, as needed for higher and higher magic-angle spinning (MAS) frequencies. Furthermore, solid-state NMR can investigate very large proteins and their complexes without the concomitant increase in line widths, motivating the use of selective labeling and unlabeling strategies, as well as segmental labeling, to decongest spectra. The possibility of investigating sub-milligram amounts of protein today using advanced fast MAS techniques enables alternative protein synthesis schemes such as cell-free expression. Here we review these specific aspects of solid-state NMR sample preparation.

Most parameters that influence the magnetic resonance imaging (MRI) signal experience a temperature dependence. The fact that MRI can be used for non-invasive measurements of temperature and temperature change deep inside the human body has been known for over 30 years. Today, MR temperature imaging is widely used to monitor and evaluate thermal therapies such as radio frequency, microwave, laser, and focused ultrasound therapy. In this paper we cover the physical principles underlying the biological applications of MR temperature imaging and discuss practical considerations and remaining challenges. For biological tissue, the MR signal of interest comes mostly from hydrogen protons of water molecules but also from protons in, e.g., adipose tissue and various metabolites. Most of the discussed methods, such as those using the proton resonance frequency (PRF) shift, T₁, T₂, and diffusion only measure temperature change, but measurements of absolute temperatures are also possible using spectroscopic imaging methods (taking advantage of various metabolite signals as internal references) or various types of contrast agents. Currently, the PRF method is the most used clinically due to good sensitivity, excellent linearity with temperature, and because it is largely independent of tissue type. Because the PRF method does not work in adipose tissues, T₁- and T₂-based methods have recently gained interest for monitoring temperature change in areas with high fat content such as the breast and abdomen. Absolute temperature measurement methods using spectroscopic imaging and contrast agents often offer too low spatial and temporal resolution for accurate monitoring of ablative thermal procedures, but have shown great promise in monitoring the slower and usually less spatially localized temperature change observed during hyperthermia procedures. Much of the current research effort for ablative procedures is aimed at providing faster measurements, larger field-of-view coverage, simultaneous monitoring in aqueous and adipose tissues, and more motion-insensitive acquisitions for better precision measurements in organs such as the heart, liver, and kidneys. For hyperthermia applications, larger coverage, motion insensitivity, and simultaneous aqueous and adipose monitoring are also important, but great effort is also aimed at solving the problem of long-term field drift which gets interpreted as temperature change when using the PRF method.

NMR is an essential technique for obtaining information at atomic resolution on the structure, motions and interactions of biomolecules. Here, we review the contribution of NMR to our understanding of the fundamental unit of chromatin: the nucleosome. Nucleosomes compact the genome by wrapping the DNA around a protein core, the histone octamer, thereby protecting genomic integrity. Crucially, the imposed barrier also allows strict regulation of gene expression, DNA replication and DNA repair processes through an intricate system of histone and DNA modifications and a wide range of interactions between nucleosomes and chromatin factors. In this review, we describe how NMR has contributed to deciphering the molecular basis of nucleosome function. Starting from pioneering studies in the 1960s using natural abundance NMR studies, we focus on the progress in sample preparation and NMR methodology that has allowed high-resolution studies on the nucleosome and its subunits. We summarize the results and approaches of state-of-the-art NMR studies on nucleosomal DNA, histone complexes, nucleosomes and nucleosomal arrays. These studies highlight the particular strength of NMR in studying nucleosome dynamics and nucleosome-protein interactions. Finally, we look ahead to exciting new possibilities that will be afforded by on-going developments in solution and solid-state NMR. By increasing both the depth and breadth of nucleosome NMR studies, it will be possible to offer a unique perspective on the dynamic landscape of nucleosomes and its interacting proteins.

Scalar couplings provide important information regarding molecular structure and dynamics. The measurement of scalar coupling constants constitutes a topic of interest and significance in NMR spectroscopy. However, the measurement of J values is often not straightforward because of complex signal splitting patterns and signal overlap. Many methods have been proposed for the measurement of scalar coupling constants, both for homonuclear and heteronuclear cases. Different approaches to the measurement of scalar coupling constants are reviewed here with several applications presented. The accurate measurement of scalar coupling constants can greatly facilitate molecular structure elucidation and the study of molecule dynamics.