Progress in Nuclear Magnetic Resonance Spectroscopy最新文献

This review deals with biological systems and with deuterium isotope effects on chemical shifts caused by the replacement of OH, NH or SH protons by deuterons. Hydrogen bonding is clearly of central importance. Isotope effects on chemical shifts seems very suitable for use in studies of structures and reactions in the interior of proteins, as exchange of the label can be expected to be slow. One-bond deuterium isotope effects on ¹⁵N chemical shifts, and two-bond effects on ¹H chemical shifts for N(D)H_x systems can be used to gauge hydrogen bond strength in proteins as well as in salt bridges. Solvent isotope effects on ¹⁹F chemical shifts show promise in monitoring solvent access. Equilibrium isotope effects need in some cases to be taken into account. Schemes for calculation of deuterium isotope effects on chemical shifts are discussed and it is demonstrated how calculations may be used in the study of complex biological systems.

Manganese ferrite nanoparticles are superparamagnetic and have very high saturation magnetization, which makes them candidates for application as MRI contrast agents. Because these nanoparticles are very effective enhancers of transverse relaxation, they are particularly suitable as negative (T₂-weighted) contrast agents. The magnitude of the relaxivity of nanoparticulate Mn ferrites seems to be determined mainly by the method of preparation, their dimensions, and their saturation magnetization.

Molecules exist in different isotopic compositions and most of the processes, physical or chemical, in living systems cause selection between heavy and light isotopes. Thus, knowing the isotopic fractionation of the common atoms, such as H, C, N, O or S, at each step during a metabolic pathway allows the construction of a unique isotope profile that reflects its past history. Having access to the isotope abundance gives valuable clues about the (bio)chemical origin of biological or synthetic molecules. Whereas the isotope ratio measured by mass spectrometry provides a global isotope composition, quantitative NMR measures isotope ratios at individual positions within a molecule. We present here the requirements and the corresponding experimental strategies to use quantitative NMR for measuring intramolecular isotope profiles. After an introduction showing the historical evolution of NMR for measuring isotope ratios, the vocabulary and symbols – for describing the isotope content and quantifying its change – are defined. Then, the theoretical framework of very accurate quantitative NMR is presented as the principle of Isotope Ratio Measurement by NMR spectroscopy, including the practical aspects with nuclei other than ²H, that have been developed and employed to date. Lastly, the most relevant applications covering three issues, tackling counterfeiting, authentication, and forensic investigation, are presented, before giving some perspectives combining technical improvements and methodological approaches.

We review methods to manipulate the motion of pulsed supersonic atomic and molecular beams using time-independent and -dependent inhomogeneous magnetic fields. In addition, we discuss current and possible future applications and research directions.

Within the field of NMR spectroscopy, the study of chemical exchange processes through saturation transfer techniques has a long history. In the context of MRI, chemical exchange techniques have been adapted to increase the sensitivity of imaging to small fractions of exchangeable protons, including the labile protons of amines, amides and hydroxyls. The MR contrast is generated by frequency-selective irradiation of the labile protons, which results in a reduction of the water signal associated with transfer of the labile protons’ saturated magnetization to the protons of the surrounding free water. The signal intensity depends on the rate of chemical exchange and the concentration of labile protons as well as on the properties of the irradiation field. This methodology is referred to as CEST (chemical exchange saturation transfer) imaging. Applications of CEST include imaging of molecules with short transverse relaxation times and mapping of physiological parameters such as pH, temperature, buffer concentration and chemical composition due to the dependency of this chemical exchange effect on all these parameters. This article aims to describe these effects both theoretically and experimentally. In depth analysis and mathematical modelling are provided for all pulse sequences designed to date to measure the chemical exchange rate. Importantly, it has become clear that the background signal from semi-solid protons and the presence of the Nuclear Overhauser Effect (NOE), either through direct dipole-dipole mechanisms or through exchange-relayed signals, complicates the analysis of CEST effects. Therefore, advanced methods to suppress these confounding factors have been developed, and these are also reviewed. Finally, the experimental work conducted both in vitro and in vivo is discussed and the progress of CEST imaging towards clinical practice is presented.

Despite its importance as a clinical imaging modality, magnetic resonance imaging remains inaccessible to most of the world’s population due to its high cost and infrastructure requirements. Substantial effort is underway to develop portable, low-cost systems able to address MRI access inequality and to enable new uses of MRI such as bedside imaging. A key barrier to development of portable MRI systems is increased magnetic field inhomogeneity when using small polarizing magnets, which degrades image quality through distortions and signal dropout. Many approaches address field inhomogeneity by using a low polarizing field, approximately ten to hundreds of milli-Tesla. At low-field, even a large relative field inhomogeneity of several thousand parts-per-million (ppm) results in resonance frequency dispersion of only 1–2 kHz. Under these conditions, with necessarily wide pulse bandwidths, fast spin-echo sequences may be used at low field with negligible subject heating, and a broad range of other available imaging sequences can be implemented. However, high-field MRI, 1.5 T or greater, can provide substantially improved signal-to-noise ratio and image contrast, so that higher spatial resolution, clinical quality images may be acquired in significantly less time than is necessary at low-field. The challenge posed by small, high-field systems is that the relative field inhomogeneity, still thousands of ppm, becomes tens of kilohertz over the imaging volume. This article describes the physical consequences of field inhomogeneity on established gradient- and spin-echo MRI sequences, and suggests ways to reduce signal dropout and image distortion from field inhomogeneity. Finally, the practicality of currently available image contrasts is reviewed when imaging with a high magnetic field with large inhomogeneity.

As structural biology trends towards larger and more complex biomolecular targets, a detailed understanding of their interactions and underlying structures and dynamics is required. The development of methyl-TROSY has enabled NMR spectroscopy to provide atomic-resolution insight into the mechanisms of large molecular assemblies in solution. However, the applicability of methyl-TROSY has been hindered by the laborious and time-consuming resonance assignment process, typically performed with domain fragmentation, site-directed mutagenesis, and analysis of NOE data in the context of a crystal structure. In response, several structure-based automatic methyl assignment strategies have been developed over the past decade. Here, we present a comprehensive analysis of all available methods and compare their input data requirements, algorithmic strategies, and reported performance. In general, the methods fall into two categories: those that primarily rely on inter-methyl NOEs, and those that utilize methyl PRE- and PCS-based restraints. We discuss their advantages and limitations, and highlight the potential benefits from standardizing and combining different methods.

Hyperpolarization techniques that can transiently boost nuclear spin polarization are generally carried out at low temperature – as in the case of dynamic nuclear polarization – or at high temperature in the gaseous state – as in the case of optically pumped noble gases. This review aims at describing the various issues and challenges that have been encountered during dissolution of hyperpolarized species, and solutions to these problems that have been or are currently proposed in the literature. During the transport of molecules from the polarizer to the NMR detection region, and when the hyperpolarized species or a precursor of hyperpolarization (e.g. parahydrogen) is introduced into the solution of interest, several obstacles need to be overcome to keep a high level of final magnetization. The choice of the magnetic field, the design of the dissolution setup, and ways to isolate hyperpolarized compounds from relaxation agents will be presented. Due to the non-equilibrium character of the hyperpolarization, new NMR pulse sequences that perform better than the classical ones will be described. Finally, three applications in the field of biology will be briefly mentioned.

Developments of NMR methodology to characterise the structures of molecular organic structures are reviewed, concentrating on the previous decade of research in which density functional theory-based calculations of NMR parameters in periodic solids have become widespread. With a focus on demonstrating the new structural insights provided, it is shown how “NMR crystallography” has been used in a spectrum of applications from resolving ambiguities in diffraction-derived structures (such as hydrogen atom positioning) to deriving complete structures in the absence of diffraction data. As well as comprehensively reviewing applications, the different aspects of the experimental and computational techniques used in NMR crystallography are surveyed. NMR crystallography is seen to be a rapidly maturing subject area that is increasingly appreciated by the wider crystallographic community.

A review of developments in fluorine NMR of relevance to synthesis, characterisation and industrial applications of small organic molecules. Developments considered include those in spectrometer technology, computational methods and pulse sequences. The review of 80 references outlines applications in areas of identification, quantitation, mixture analysis, reaction monitoring, environmental studies and fragment-based drug design.