J-driven Dynamic Nuclear Polarization for sensitizing high field solution state NMR

Dynamic nuclear polarization (DNP) is widely used to enhance solid state nuclear magnetic resonance (NMR) sensitivity. Its efficiency as a generic signal-enhancing approach for liquid state NMR, however, decays rapidly...

NMR Relaxivities of Paramagnetic Lanthanide-Containing Polyoxometalates

The current trend for ultra-high-field magnetic resonance imaging (MRI) technologies opens up new routes in clinical diagnostic imaging as well as in material imaging applications. MRI selectivity is further improved by using contrast agents (CAs), which enhance the image contrast and improve specificity by the paramagnetic relaxation enhancement (PRE) mechanism. Generally, the efficacy of a CA at a given magnetic field is measured by its longitudinal and transverse relaxivities r1 and r2, i.e., the longitudinal and transverse relaxation rates T1−1 and T2−1 normalized to CA concentration. However, even though basic NMR sensitivity and resolution become better in stronger fields, r1 of classic CA generally decreases, which often causes a reduction of the image contrast. In this regard, there is a growing interest in the development of new contrast agents that would be suitable to work at higher magnetic fields. One of the strategies to increase imaging contrast at high magnetic field is to inspect other paramagnetic ions than the commonly used Gd(III)-based CAs. For lanthanides, the magnetic moment can be higher than that of the isotropic Gd(III) ion. In addition, the symmetry of electronic ground state influences the PRE properties of a compound apart from diverse correlation times. In this work, PRE of water 1H has been investigated over a wide range of magnetic fields for aqueous solutions of the lanthanide containing polyoxometalates [DyIII(H2O)4GeW11O39]5– (Dy-W11), [ErIII(H2O)3GeW11O39]5– (Er-W11) and [{ErIII(H2O)(CH3COO)(P2W17O61)}2]16− (Er2-W34) over a wide range of frequencies from 20 MHz to 1.4 GHz. Their relaxivities r1 and r2 increase with increasing applied fields. These results indicate that the three chosen POM systems are potential candidates for contrast agents, especially at high magnetic fields.

Bulk Hyperpolarization of Inorganic Materials

Solid-state NMR spectroscopy is a well-established method to obtain atomic-level information about the structure of inorganic materials, but its use is often limited by low sensitivity. We review how solvent generated dynamic nuclear polarization can be used to increase sensitivity in solid-state NMR of inorganic materials, with emphasis on our recent method for hyperpolarization of proton-free bulk. We use selected examples to show how overall gains in sensitivity can be observed in both the surface and bulk spectra of inorganic compounds such as lithium titanate. The hyperpolarization methods reviewed here can be used to improve NMR sensitivity for a range of inorganic materials.

Monitoring of the Pre-Equilibrium Step in the Alkyne Hydration Reaction Catalyzed by Au(III) Complexes: A Computational Study Based on Experimental Evidences

The coordination ability of the [(ppy)Au(IPr)]2+ fragment [ppy = 2-phenylpyridine, IPr = 1,3-bis(2,6-di-isopropylphenyl)-imidazol-2-ylidene] towards different anionic and neutral X ligands (X = Cl−, BF4−, OTf−, H2O, 2-butyne, 3-hexyne) commonly involved in the crucial pre-equilibrium step of the alkyne hydration reaction is computationally investigated to shed light on unexpected experimental observations on its catalytic activity. Experiment reveals that BF4− and OTf− have very similar coordination ability towards [(ppy)Au(IPr)]2+ and slightly less than water, whereas the alkyne complex could not be observed in solution at least at the NMR sensitivity. Due to the steric hindrance/dispersion interaction balance between X and IPr, the [(ppy)Au(IPr)]2+ fragment is computationally found to be much less selective than a model [(ppy)Au(NHC)]2+ (NHC = 1,3-dimethylimidazol-2-ylidene) fragment towards the different ligands, in particular OTf− and BF4−, in agreement with experiment. Effect of the ancillary ligand substitution demonstrates that the coordination ability of Au(III) is quantitatively strongly affected by the nature of the ligands (even more than the net charge of the complex) and that all the investigated gold fragments coordinate to alkynes more strongly than H2O. Remarkably, a stabilization of the water-coordinating species with respect to the alkyne-coordinating one can only be achieved within a microsolvation model, which reconciles theory with experiment. All the results reported here suggest that both the Au(III) fragment coordination ability and its proper computational modelling in the experimental conditions are fundamental issues for the design of efficient catalysts.

Parahydrogen hyperpolarization of minimally altered urine samples for sensitivity enhanced NMR metabolomics

Parahydrogen hyperpolarization has been shown to enhance NMR sensitivity in urine analysis by several orders of magnitude if urine samples are prepared by solid phase extraction (SPE). We present a...

A 300-fold enhancement of imino nucleic acid resonances by hyperpolarized water provides a new window for probing RNA refolding by 1D and 2D NMR

NMR sensitivity-enhancement methods involving hyperpolarized water could be of importance for solution-state biophysical investigations. Hyperpolarized water (HyperW) can enhance the 1H NMR signals of exchangeable sites by orders of magnitude over their thermal counterparts, while providing insight into chemical exchange and solvent accessibility at a site-resolved level. As HyperW’s enhancements are achieved by exploiting fast solvent exchanges associated with minimal interscan delays, possibilities for the rapid monitoring of chemical reactions and biomolecular (re)folding are opened. HyperW NMR can also accommodate heteronuclear transfers, facilitating the rapid acquisition of 2-dimensional (2D) 15N-1H NMR correlations, and thereby combining an enhanced spectral resolution with speed and sensitivity. This work demonstrates how these qualities can come together for the study of nucleic acids. HyperW injections were used to target the guanine-sensing riboswitch aptamer domain (GSRapt) of the xpt-pbuX operon in Bacillus subtilis. Unlike what had been observed in proteins, where residues benefited of HyperW NMR only if/when sufficiently exposed to water, these enhancements applied to every imino resonance throughout the RNA. The >300-fold enhancements observed in the resulting 1H NMR spectra allowed us to monitor in real time the changes that GSRapt undergoes upon binding hypoxanthine, a high-affinity interaction leading to conformational refolding on a ∼1-s timescale at 36 °C. Structural responses could be identified for several nucleotides by 1-dimensional (1D) imino 1H NMR as well as by 2D HyperW NMR spectra acquired upon simultaneous injection of hyperpolarized water and hypoxanthine. The folding landscape revealed by this HyperW strategy for GSRapt, is briefly discussed.

Enhancing benchtop NMR spectroscopy by means of sample shifting

Benchtop NMR sensitivity enhancement by cyclic, mechanical shifting of a sample to preserve high nuclear spin polarization.

Tunable iridium catalyst designs with bidentate N-heterocyclic carbene ligands for SABRE hyperpolarization of sterically hindered substrates

A series of iridium catalysts provides NMR sensitivity enhancement using para-hydrogen. The substrate exchange rate can be tuned for optimal polarization by the choice of an aryl and a nucleophilic moiety in the catalyst.