Dynamic nuclear polarization (DNP) can boost sensitivity in nuclear magnetic resonance (NMR) experiments by several orders of magnitude. This Feature illustrates how the coupling of DNP with both ...liquid- and solid-state NMR spectroscopy has the potential to considerably extend the range of applications of NMR in analytical chemistry.
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•dDNP is a powerful tool for real-time monitoring of chemical reactions and biochemical interactions.•DNP yields the potential of promising applications including metabolomics and ...protein structural dynamics.•Higher-dimensional NMR and ultrafast methods coupled to d-DNP enable high-resolution studies of complex soft matter.•Recent methodological developments hint towards the development of “transportable hyperpolarization”.
Dissolution dynamic nuclear polarization (d-DNP) is a versatile method to enhance nuclear magnetic resonance (NMR) spectroscopy. It boosts signal intensities by four to five orders of magnitude thereby providing the potential to improve and enable a plethora of applications ranging from the real-time monitoring of chemical or biological processes to metabolomics and in-cell investigations. This perspectives article highlights possible avenues for developments and applications of d-DNP in biochemical and physicochemical studies. It outlines how chemists, biologists and physicists with various fields of interest can transform and employ d-DNP as a powerful characterization method for their research.
Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. ...Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g
. Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P(
C) = 25% within 8 min, through the combination of
H spin diffusion and
H →
C cross polarization. Solutions of
C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state
C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances.
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This article is a short review of some of our recent developments in dissolution dynamic nuclear polarization (d-DNP). We present the basic principles of d-DNP, and motivate our ...choice to step away from conventional approaches. We then introduce a modified d-DNP recipe that can be summed up as follows:
(i)Using broad line polarizing agents to efficiently polarize 1H spins.(ii)Increasing the magnetic field to 6.7T and above.(iii)Applying microwave frequency modulation.(iv)Applying 1H–13C cross polarization.(v)Transferring hyperpolarized solution through a magnetic tunnel.
Nuclear spin hyperpolarization of
C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in ...vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude.
Practical dissolution dynamic nuclear polarization Elliott, Stuart J.; Stern, Quentin; Ceillier, Morgan ...
Progress in nuclear magnetic resonance spectroscopy,
October-December 2021, 2021 Oct-Dec, 2021-10-00, 20211001, 2021-10, Letnik:
126-127
Journal Article
Recenzirano
Odprti dostop
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•A practical overview of dissolution dynamic nuclear polarization (dDNP) is given.•Hands-on guidance is presented for a wide range of topics relevant to dDNP.•We mostly focus on ...experimental formulas, recipes and hardware innovations.•We showcase limitations of dDNP experiments and common reasons for failure.•Simple resolutions to overcome common pitfalls of dDNP experiments are provided.
This review article intends to provide insightful advice for dissolution-dynamic nuclear polarization in the form of a practical handbook. The goal is to aid research groups to effectively perform such experiments in their own laboratories. Previous review articles on this subject have covered a large number of useful topics including instrumentation, experimentation, theory, etc. The topics to be addressed here will include tips for sample preparation and for checking sample health; a checklist to correctly diagnose system faults and perform general maintenance; the necessary mechanical requirements regarding sample dissolution; and aids for accurate, fast and reliable polarization quantification. Herein, the challenges and limitations of each stage of a typical dissolution-dynamic nuclear polarization experiment are presented, with the focus being on how to quickly and simply overcome some of the limitations often encountered in the laboratory.
The affinity between a chosen target protein and small molecules is a key aspect of drug discovery. Screening by popular NMR methods such as Water-LOGSY suffers from low sensitivity and from false ...positives caused by aggregated or denatured proteins. This work demonstrates that the sensitivity of Water-LOGSY can be greatly boosted by injecting hyperpolarized water into solutions of proteins and ligands. Ligand binding can be detected in a few seconds, whereas about 30 min is usually required without hyperpolarization. Hyperpolarized water also enhances proton signals of proteins at concentrations below 20 μM so that one can verify in a few seconds whether the proteins remain intact or have been denatured
In deuterated molecules such as 1-13Cpyruvate-d 3, the nuclear spin polarization of 13C nuclei can be enhanced by combining Hartmann–Hahn cross-polarization (CP) at low temperatures (1.2 K) with ...dissolution dynamic nuclear polarization (D-DNP). The polarization is transferred from remote solvent protons to the 13C spins of interest. This allows one not only to slightly reduce build-up times but also to increase polarization levels and extend the lifetimes T 1(13C) of the enhanced 13C polarization during and after transfer from the polarizer to the NMR or MRI system. This extends time scales over which metabolic processes and chemical reactions can be monitored.
Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of ...polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion.
Significance Hyperpolarization by dissolution dynamic nuclear polarization can dramatically enhance signal intensities in MRI and NMR, notably for metabolic tracers for imaging and diagnosis. It is applicable to a variety of substrates for in vivo imaging and chemistry but requires the use of contaminants (glassing agents and free radicals) that may interact with cells and proteins and can have potential side effects. These contaminants can sometimes be eliminated by precipitation followed by filtration or solvent extraction, but these methods are substrate-specific, are usually time-consuming, and typically result in signal loss. Here, production of pure hyperpolarized liquids free of contaminants is shown by a simple wetting–polarization–filtration sequence for a solid silica matrix containing homogeneously distributed persistent radicals.
Tailoring the physical features and the porous network architecture of silica‐based hyperpolarizing solids containing TEMPO radicals, known as HYPSO (hybrid polarizing solids), enabled unprecedented ...performance of dissolution dynamic nuclear polarization (d‐DNP). High polarization values up to P(1H)=99 % were reached for samples impregnated with a mixture of H2O/D2O and loaded in a 6.7 T polarizer at temperatures around 1.2 K. These HYPSO materials combine the best performance of homogeneous DNP formulations with the advantages of solid polarizing matrices, which provide hyperpolarized solutions free of any—potentially toxic—additives (radicals and glass‐forming agents). The hyperpolarized solutions can be expelled from the porous solids, filtered, and rapidly transferred either to a nuclear magnetic resonance (NMR) spectrometer or to a magnetic resonance imaging (MRI) system.
A matter of polarization: Porous silica‐based solids functionalized with TEMPO surface groups were designed and used to achieve remarkable proton and carbon polarization values by dynamic nuclear polarization. These materials were successfully used as polarizing matrices for 13C magnetic resonance imaging.
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