Magnetic resonance imaging (MRI) is increasingly used for quantitative in-vivo measurements, including measurement of biomarkers based on relaxation times, diffusion, flow, temperature, local concentration of neurotransmitters and metabolites, tissue conductivity/dielectric constant, as well as geometrical parameters such as volume, shape, and texture. MRI based biomarkers vary widely, each with different degrees of utility, robustness, and accuracy. The hope is that quantitative measurements will have less site-to-site and scanner-to-scanner variability, less susceptibility to artifacts, less interpretation variation, and higher information content. Making in-vivo MRI-based measurements accurate and traceable is very challenging. MRI is a spatially resolved form of nuclear magnetic resonance (NMR), which has a long history of precise quantitative measurements. However, in-vivo MRI has many constraints that compete with measurement precision including safety, time, cost, comfort, and integration with clinical workflows. Further, living tissue is a complex nonuniform, nonequilibrium system that is often difficult to characterize with a small set of well-defined macroscopic parameters. The accuracy of a biomarker measurement is tied to the accuracy of the underlying model, which is most often approximate. Here, we describe NMR-based calibration standards developed to improve the accuracy of MRI-based measurements. The standards are part of a traceability path from NMR, to ex-vivo MRI, and then to in-vivo MRI. Physical standards discussed here are incorporated into phantoms (image calibration objects) and are a small, but critical, part of a larger standards infrastructure that includes standardized imaging protocols, data analysis, data interpretation, data archiving and retrieval.
There is widespread adoption of methods for nuclear magnetic resonance data acquisition and processing that are based on non-consecutive sampling, generally in indirect evolution periods but with some growing uses in direct acquisition, and broadly termed non-uniform sampling (NUS). This Report summarizes recent advances in NUS and key emerging applications. The emergence of low rank matrix methods and deep learning methods distinguish a good deal of new work, while an improved understanding of NUS schedule principles has also taken place. Numerous spectral analysis and reconstruction approaches have been tested more fully in this period, ushering in more rigorous comparisons and tests of fidelity. Available spectral reconstruction methods show differences, but also generally perform robustly if applied appropriately. Non-uniform sampling strategies are being applied to increasingly challenging experiments and systems. A review of the current terminology in NUS, which has grown in recent years, is summarized as well. Selected applications in several areas, such as in metabolomics and reaction monitoring, are covered.
In this review, we outline the ways in which NMR spectroscopy has been deployed to observe highly reactive, short-lived species, using sigma-alkane complexes as a case study. sigma-Alkane complexes feature an alkane molecule acting as a ligand that is weakly bound to a transition metal. Although difficult to observe because of their transient nature, well defined sigma-alkane complexes are now becoming established due to the developments in characterisation techniques alongside synthetic methodologies that allow for their observation. Although the number of such complexes remains relatively small compared to other sigma-complexes, their growing number and diversity promises much for the future in terms of the elucidation of their role in selective C-H bond activation and functionalisation. We discuss the innovative strategies that have been used and outline how these NMR experiments may be applied to studies of other transient species. We also present the results from these NMR experiments applied to sigma-alkane complexes, with emphasis on recent results and the techniques developed.
NMR spectroscopy is a powerful analytical technique that has been one of the key technologies in chemistry, particular for compound identification, structure elucidation and reaction monitoring, for the past 70 years. While an essential tool of the modern chemist, standard NMR instruments are large, complex, expensive to run and require specialised facilities and staff to use. This limits their accessibility to many researchers, both academic and industrial. Advances in technology over the last decade have led to the development of benchtop NMR instruments. These are smaller, less expensive, and easier to use than traditional instruments. They are capable of Fourier transform NMR and relaxometry measurements and have been used in applications as diverse as the analysis of illegal drugs to exploring interactions in zeolites and other porous materials. Trying to capture all the applications of benchtop NMR would be rather difficult so in this chapter, we will discuss the foundations of benchtop Fourier transform and relaxometry NMR and showcase some of the major applications of these techniques. We show how miniaturisation of NMR has driven, and will continue to drive, innovations and advances in many areas of chemistry and give a detailed overview of the state of the science. Focus is paid to areas that are currently underserved by conventional NMR including food, environmental and material science, catalysis, and the energy industry. Citations to relevant reviews and articles are included for more details on specific applications.
Over the past two-three decades, solvent-relaxation NMR has become an established tool for probing the composition of near-particle-surface structures of aqueous particulate dispersions via the effective surface area present. Yet, the universality of the technique has not been fully explored in non-aqueous systems. To this end, particulate dispersions comprising non-aqueous and mixed aqueous-non-aqueous solvents have been analysed. In all cases, there is the required linear relationship between the surface area present and the experimentally observed solvent-relaxation rate, illustrating the universality of the methodology in studying non-aqueous systems. Practically, this "surface enhancement" effect is considerably weaker in nonaqueous systems compared with aqueous dispersions, perhaps reflecting a potential limitation of the wider deployment of this experimental methodology. Furthermore, it is shown here that processes occurring in unstable colloidal dispersions-settling, creaming, dewatering-can also be characterised by measuring the solvent-relaxation rate in such systems over time. These processes will be illustrated by demonstrating the effects of nanoparticle concentration, electrolyte type, and pH on the stability of aqueous mineral dispersions, with correlation to the visually determined phase behaviour. In addition, the adsorption of polymer and surfactant at particle surface area have been reviewed.
Analysis of complex mixtures is of main interest since they are ubiquitous in the nature. Thus, it becomes challenging to decipher their complexity by developing NMR methods able to identify but also to quantify molecules in the most accurate way. 1D H-1 NMR is highly utilized for quantifying molecules but suffers from many overlaps making this approach limited. 2D NMR is a great manner to improve the signal dispersion over 2 dimensions and the H-1-C-13 HSQC experiment is the best choice to improve the spectral resolution despite a lower sensitivity. However, due to its multiple pulse nature, the quantitativity of HSQC is impacted and biased absolute concentrations are derived. In this chapter, we highlight the potential of a class of methods called intrinsically quantitative 2D HSQC. They are generated by designing pulse sequences able for each correlation peak to maintain constant or to compensate J(HH), J(CH), off resonances and T-2 effects responsible for the degradation of the quantitativity. Pioneer experiments as Q-HSQC and HSQC(0) are detailed as well as their improved versions and applicative examples are given. Then, these major techniques are compared to show their performances and limits. Finally, recent methodological developments are proposed and discussed to enhance the potential of future intrinsically quantitative 2D-based complex mixture analyses.
For a comprehensive understanding, the structure and function of molecules and molecular complexes should be investigated in their operational environment. To this end, many efforts have been made to develop in-situ biological spectroscopy. In the late 1970s, the intact enveloped virus PM2 was studied by 31P wide-line NMR, because of its simplicity, lipid envelope, and high yield, and it was possible to obtain in-situ information about the membrane and infectivity. The dynamic structures of the chromosomes were then analysed by 31P cross-polarisation NMR. Once the high-resolution solid-state NMR was established, cell walls and cell components were extensively investigated in situ using specific isotope-labelling. Dynamic nuclear polarisation (DNP) was also used to increase sensitivity. The intact structure of a light-harvesting device, the chlorosome, could be determined by uniform 13C-labelling and the proton-driven spin-diffusion caused by 13C–13C dipolar interactions, because the basic unit, bacteriochlorophyll c, was relatively small. Currently, in-situ analysis of photo-intermediates of a photoreceptor protein has been carried out using photo-illumination, cryo-trapping and DNP. Thermodynamic parameters regulating the energy transduction at the Foa–c subunit interface have been estimated from the structure analysis of a biological molecular motor, FoF1ATP synthase, using specific SAIL-labelling and in-situ CP/MAS-NMR.
Lyotropic lipidic cubic phases (LCPs), a subgroup of liquid-crystalline mesophases, are formed spontaneously via the self-assembly of certain lipids in an aqueous environment within a defined range of temperature. Nowadays, LCPs are deeply rooted in the crystallization of integral membrane proteins for their structural characterization by X-ray crystallography. Moreover, these nanomaterials are highly prospective drug and nutrient carriers and release matrices. Nuclear magnetic resonance spectroscopy, both solution and solid-state, has traditionally been used for the characterization of lipid and surfactant systems, including LCPs. In this Chapter, a number of recently reported studies involving the analysis of LCPs by solution NMR and PGSE NMR spectroscopy are examined and some future perspectives discussed. These include the quantification of hydration, long-term stability, additive lipid induced 13C chemical shift perturbations, hydration dynamics, chemical exchange, 13C relaxation-based analyses of hydrocarbon chain dynamics, and encapsulation of soluble globular proteins.
