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1. “Direct” ¹³ C Hyperpolarization of ¹³ C‐Acetate by MicroTesla NMR Signal Amplification by Reversible Exchange (SABRE)

   https://doi.org/10.1002/anie.201910506  

   Gemeinhardt, Max E.; Limbach, Miranda N.; Gebhardt, Thomas R.; Eriksson, Clark W.; Eriksson, Shannon L.; Lindale, Jacob R.; Goodson, Elysia A.; Warren, Warren S.; Chekmenev, Eduard Y.; Goodson, Boyd M. (November 2019, Angewandte Chemie International Edition)

   Abstract Herein, we demonstrate “direct”¹³C hyperpolarization of¹³C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐¹³C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the¹³C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of “direct” transfer of spin order from parahydrogen to¹³C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the¹³C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism. 

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2. NMR Crystallography: Evaluation of Hydrogen Positions in Hydromagnesite by ¹³ C{ ¹ H} REDOR Solid‐State NMR and Density Functional Theory Calculation of Chemical Shielding Tensors

   https://doi.org/10.1002/anie.201813306  

   Cui, Jinlei; Olmsted, David L.; Mehta, Anil K.; Asta, Mark; Hayes, Sophia E. (February 2019, Angewandte Chemie International Edition)

   Abstract Solid‐state NMR measurements coupled with density functional theory (DFT) calculations demonstrate how hydrogen positions can be refined in a crystalline system. The precision afforded by rotational‐echo double‐resonance (REDOR) NMR to interrogate¹³C–¹H distances is exploited along with DFT determinations of the¹³C tensor of carbonates (CO₃²⁻). Nearby¹H nuclei perturb the axial symmetry of the carbonate sites in the hydrated carbonate mineral, hydromagnesite [4 MgCO₃⋅Mg(OH)₂⋅4 H₂O]. A match between the calculated structure and solid‐state NMR was found by testing multiple semi‐local and dispersion‐corrected DFT functionals and applying them to optimize atom positions, starting from X‐ray diffraction (XRD)‐determined atomic coordinates. This was validated by comparing calculated to experimental¹³C{¹H} REDOR and¹³C chemical shift anisotropy (CSA) tensor values. The results show that the combination of solid‐state NMR, XRD, and DFT can improve structure refinement for hydrated materials. 

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3. Order‐Unity ¹³ C Nuclear Polarization of [1‐ ¹³ C]Pyruvate in Seconds and the Interplay of Water and SABRE Enhancement

   https://doi.org/10.1002/cphc.202100839  

   Adelabu, Isaiah; TomHon, Patrick; Kabir, Mohammad S. H.; Nantogma, Shiraz; Abdulmojeed, Mustapha; Mandzhieva, Iuliia; Ettedgui, Jessica; Swenson, Rolf E.; Krishna, Murali C.; Theis, Thomas; et al (December 2021, ChemPhysChem)

   Abstract Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE‐SHEATH) is investigated to achieve rapid hyperpolarization of¹³C₁spins of [1‐¹³C]pyruvate, using parahydrogen as the source of nuclear spin order. Pyruvate exchange with an iridium polarization transfer complex can be modulated via a sensitive interplay between temperature and co‐ligation of DMSO and H₂O. Order‐unity¹³C (>50 %) polarization of catalyst‐bound [1‐¹³C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1‐¹³C]pyruvate at lower temperatures. On the catalyst bound pyruvate, 39 % polarization is measured using a 1.4 T NMR spectrometer, and extrapolated to >50 % at the end of build‐up in situ. The highest measured polarization of a 30‐mM pyruvate sample, including free and bound pyruvate is 13 % when using 20 mM DMSO and 0.5 M water in CD₃OD. Efficient¹³C polarization is also enabled by favorable relaxation dynamics in sub‐microtesla magnetic fields, as indicated by fast polarization buildup rates compared to theT₁spin‐relaxation rates (e. g., ∼0.2 s⁻¹versus ∼0.1 s⁻¹, respectively, for a 6 mM catalyst‐[1‐¹³C]pyruvate sample). Finally, the catalyst‐bound hyperpolarized [1‐¹³C]pyruvate can be released rapidly by cycling the temperature and/or by optimizing the amount of water, paving the way to future biomedical applications of hyperpolarized [1‐¹³C]pyruvate produced via comparatively fast and simple SABRE‐SHEATH‐based approaches. 

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4. Fast Magic‐Angle Spinning ¹⁹ F NMR Spectroscopy of HIV‐1 Capsid Protein Assemblies

   https://doi.org/10.1002/anie.201809060  

   Wang, Mingzhang; Lu, Manman; Fritz, Matthew P.; Quinn, Caitlin M.; Byeon, In‐Ja L.; Byeon, Chang‐Hyeock; Struppe, Jochem; Maas, Werner; Gronenborn, Angela M.; Polenova, Tatyana (October 2018, Angewandte Chemie International Edition)

   Abstract ¹⁹F NMR spectroscopy is an attractive and growing area of research with broad applications in biochemistry, chemical biology, medicinal chemistry, and materials science. We have explored fast magic angle spinning (MAS)¹⁹F solid‐state NMR spectroscopy in assemblies of HIV‐1 capsid protein. Tryptophan residues with fluorine substitution at the 5‐position of the indole ring were used as the reporters. The¹⁹F chemical shifts for the five tryptophan residues are distinct, reflecting differences in their local environment. Spin‐diffusion and radio‐frequency‐driven‐recoupling experiments were performed at MAS frequencies of 35 kHz and 40–60 kHz, respectively. Fast MAS frequencies of 40–60 kHz are essential for consistently establishing¹⁹F–¹⁹F correlations, yielding interatomic distances of the order of 20 Å. Our results demonstrate the potential of fast MAS¹⁹F NMR spectroscopy for structural analysis in large biological assemblies. 

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5. Enhancing the resolution of ¹ H and ¹³ C solid-state NMR spectra by reduction of anisotropic bulk magnetic susceptibility broadening

   https://doi.org/10.1039/C7CP04223J  

   Hanrahan, Michael P.; Venkatesh, Amrit; Carnahan, Scott L.; Calahan, Julie L.; Lubach, Joseph W.; Munson, Eric J.; Rossini, Aaron J. (January 2017, Phys. Chem. Chem. Phys.)

   We demonstrate that natural isotopic abundance 2D heteronuclear correlation (HETCOR) solid-state NMR spectra can be used to significantly reduce or eliminate the broadening of 1 H and 13 C solid-state NMR spectra of organic solids due to anisotropic bulk magnetic susceptibility (ABMS). ABMS often manifests in solids with aromatic groups, such as active pharmaceutical ingredients (APIs), and inhomogeneously broadens the NMR peaks of all nuclei in the sample. Inhomogeneous peaks with full widths at half maximum (FWHM) of ∼1 ppm typically result from ABMS broadening and the low spectral resolution impedes the analysis of solid-state NMR spectra. ABMS broadening of solid-state NMR spectra has previously been eliminated using 2D multiple-quantum correlation experiments, or by performing NMR experiments on diluted materials or single crystals. However, these experiments are often infeasible due to their poor sensitivity and/or provide limited gains in resolution. 2D 1 H– 13 C HETCOR experiments have previously been applied to reduce susceptibility broadening in paramagnetic solids and we show that this strategy can significantly reduce ABMS broadening in diamagnetic organic solids. Comparisons of 1D solid-state NMR spectra and 1 H and 13 C solid-state NMR spectra obtained from 2D 1 H– 13 C HETCOR NMR spectra show that the HETCOR spectrum directly increases resolution by a factor of 1.5 to 8. The direct gain in resolution is determined by the ratio of the inhomogeneous 13 C/ 1 H linewidth to the homogeneous 1 H linewidth, with the former depending on the magnitude of the ABMS broadening and the strength of the applied field and the latter on the efficiency of homonuclear decoupling. The direct gains in resolution obtained using the 2D HETCOR experiments are better than that obtained by dilution. For solids with long proton longitudinal relaxation times, dynamic nuclear polarization (DNP) was applied to enhance sensitivity and enable the acquisition of 2D 1 H– 13 C HETCOR NMR spectra. 2D 1 H– 13 C HETCOR experiments were applied to resolve and partially assign the NMR signals of the form I and form II polymorphs of aspirin in a sample containing both forms. These findings have important implications for ultra-high field NMR experiments, optimization of decoupling schemes and assessment of the fundamental limits on the resolution of solid-state NMR spectra. 

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