H-F cross-polarization magic angle spinning dynamic nuclear polarization NMR investigation of advanced pharmaceutical formulations.

A new 3.2 mm H-F-X magic angle spinning dynamic nuclear polarization NMR (MAS DNP-NMR) probe was developed with a unique coil design with separate radiofrequency channels for H excitation and C or F detection to enable acquisition of H-F cross-polarization (CP) MAS experiments, direct-detected F spectra with proton decoupling, and acquisition on C with simultaneous double decoupling on the H and 19F channels as well as H-F-C double-CP experiments under low temperature MAS DNP conditions. We use these sequences to study AZD2811, which is an active pharmaceutical ingredient (API), in its pure dry state as well as in its corresponding drug delivery formulation consisting of drug-loaded polymeric nanoparticles (PNPs).

Boosting H and C NMR signals by orders of magnitude on a bench.

Sensitivity is often the Achilles' heel of liquid-state nuclear magnetic resonance (NMR) experiments. This problem is perhaps most pressing at the lowest fields (e.g.

Full optimization of dynamic nuclear polarization on a 1 tesla benchtop polarizer with hyperpolarizing solids.

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) provides the opportunity to dramatically increase the weak nuclear magnetic resonance (NMR) signal of liquid molecular targets using the high polarization of electron radicals. Unfortunately, the solution-state hyperpolarization can only be accessed once since freezing and melting of the hyperpolarized sample happen in an irreversible fashion. A way to expand the application horizon of dDNP can therefore be to find a recyclable DNP alternative.

Fine optimization of a dissolution dynamic nuclear polarization experimental setting for C NMR of metabolic samples.

NMR-based analysis of metabolite mixtures provides crucial information on biological systems but mostly relies on 1D H experiments for maximizing sensitivity. However, strong peak overlap of H spectra often is a limitation for the analysis of inherently complex biological mixtures. Dissolution dynamic nuclear polarization (d-DNP) improves NMR sensitivity by several orders of magnitude, which enables C NMR-based analysis of metabolites at natural abundance.

Porous functionalized polymers enable generating and transporting hyperpolarized mixtures of metabolites.

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.

Pulse sequence and sample formulation optimization for dipolar order mediated H→C cross-polarization.

We have recently demonstrated the use of contactless radiofrequency pulse sequences under dissolution-dynamic nuclear polarization conditions as an attractive way of transferring polarization from sensitive 1H spins to insensitive 13C spins with low peak radiofrequency pulse powers and energies via a reservoir of dipolar order. However, many factors remain to be investigated and optimized to enable the full potential of this polarization transfer process. We demonstrate herein the optimization of several key factors by: (i) implementing more efficient shaped radiofrequency pulses; (ii) adapting 13C spin labelling; and (iii) avoiding methyl group relaxation sinks.

Hyperpolarized NMR Metabolomics at Natural C Abundance.

Metabolomics plays a pivotal role in systems biology, and NMR is a central tool with high precision and exceptional resolution of chemical information. Most NMR metabolomic studies are based on H 1D spectroscopy, severely limited by peak overlap. C NMR benefits from a larger signal dispersion but is barely used in metabolomics due to ca.

Hyperpolarization of nitrogen-15 nuclei by cross polarization and dissolution dynamic nuclear polarization.

Dynamic Nuclear Polarization (DNP) is often achieved by the direct transfer of polarization from electrons to nuclei such as C, induced by microwave saturation of the wings of narrow EPR lines of radicals like trityl. In the indirect approach on the other hand, DNP is used to transfer the polarization from the electrons of radicals such as nitroxides that have broad EPR lines to nuclear spins I = H, followed by cross-polarization (CP) from I = H to S = C or other nuclei with low gyromagnetic ratios. This approach is particularly attractive for S = N, since direct DNP yields modest polarizations P(N) < 4% with build-up times that can be as long as τ(N) > 2 h.

Dissolution dynamic nuclear polarization of deuterated molecules enhanced by cross-polarization.

We present novel means to hyperpolarize deuterium nuclei in CD groups at cryogenic temperatures. The method is based on cross-polarization from H to C and does not require any radio-frequency fields applied to the deuterium nuclei. After rapid dissolution, a new class of long-lived spin states can be detected indirectly by C NMR in solution.

Cross polarization from (1)H to quadrupolar (6)Li nuclei for dissolution DNP.

Cross polarization from protons to quadrupolar (6)Li nuclei is combined with dynamic nuclear polarization of protons at 1.2 K and 6.7 T using TEMPOL as a polarizing agent followed by rapid dissolution.

Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization.

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).

Hyperpolarization of deuterated metabolites via remote cross-polarization and dissolution dynamic nuclear polarization.

In deuterated molecules such as [1-(13)C]pyruvate-d3, the nuclear spin polarization of (13)C 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 (13)C spins of interest.

Boosting Dissolution Dynamic Nuclear Polarization by Cross Polarization.

The efficiency of dissolution dynamic nuclear polarization can be boosted by Hartmann-Hahn cross polarization at temperatures near 1.2 K. This enables high throughput of hyperpolarized solutions with substantial gains in buildup times and polarization levels.

Large surface mapping by a unilateral NMR scanner.

The nuclear magnetic resonance (NMR) surface scanner, which provides images of sample surfaces larger than the probe dimension, has been realized using a single-sided device. Although conditioned by distortion effects originated by convolution between the sensitive volume of the probe and the space structures to be imaged, the scanner is able to provide images with good spatial resolution. The images obtained by the surface scanner can be made sensitive to relaxation parameters, magnetization or molecular self-diffusion; also, the dimension perpendicular to the sample surface can be scanned by varying the depth from which the probe detects the sample signal.

(EDT-TTF-CONH2)6[Re6Se8(CN)6], a metallic Kagome-type organic-inorganic hybrid compound: electronic instability, molecular motion, and charge localization.

(EDT-TTF-CONH2)6[Re6Se8(CN)6], space group R, was prepared by electrocrystallization from the primary amide-functionalized ethylenedithiotetrathiafulvalene, EDT-TTF-CONH2 (E(1/2)1 = 0.49 V vs SCE in CH3CN), and the molecular cluster tetraanion, [Re6Se8(CN)6]4- (E(1/2) = 0.33 V vs SCE in CH3CN), equipped with hydrogen bond donor and hydrogen bond acceptor functionalities, respectively.