Solution -Proline Conformation of IPCs Inhibitor Aureobasidin A Elucidated via NMR-Based Conformational Analysis.

Aureobasidin A (abA) is a natural depsipeptide that inhibits inositol phosphorylceramide (IPC) synthases with significant broad-spectrum antifungal activity. abA is known to have two distinct conformations in solution corresponding to and -proline (Pro) amide bond rotamers. While the -Pro conformation has been studied extensively, -Pro conformers have remained elusive.

Cryogen-free dissolution dynamic nuclear polarization polarizer operating at 3.35 T, 6.70 T, and 10.1 T.

Purpose: A novel dissolution dynamic nuclear polarization (dDNP) polarizer platform is presented. The polarizer meets a number of key requirements for in vitro, preclinical, and clinical applications.

Method: It uses no liquid cryogens, operates in continuous mode, accommodates a wide range of sample sizes up to and including those required for human studies, and is fully automated.

Simultaneous imaging of hyperpolarized [1,4- C ]fumarate, [1- C]pyruvate and F-FDG in a rat model of necrosis in a clinical PET/MR scanner.

A co-polarization scheme for [1,4- C ]fumarate and [1- C]pyruvate is presented to simultaneously assess necrosis and metabolism in rats with hyperpolarized C magnetic resonance (MR). The co-polarization was performed in a SPINlab polarizer. In addition, the feasibility of simultaneous positron emission tomography (PET) and MR of small animals with a clinical PET/MR scanner is demonstrated.

Large dose hyperpolarized water with dissolution-DNP at high magnetic field.

We demonstrate a method for the preparation of hyperpolarized water by dissolution Dynamic Nuclear Polarization at high magnetic field. Protons were polarized at 6.7T and 1.

Waveguide transition with vacuum window for multiband dynamic nuclear polarization systems.

A low loss waveguide transition section and oversized microwave vacuum window covering several frequency bands (94 GHz, 140 GHz, 188 GHz) is presented. The transition is compact and was optimized for multiband Dynamic Nuclear Polarization (DNP) systems in a full-wave simulator. The window is more broadband than commercially available windows, which are usually optimized for single band operation.

Dissolution dynamic nuclear polarization of non-self-glassing agents: spectroscopy and relaxation of hyperpolarized [1-13C]acetate.

The intrinsic physicochemical properties of the sample formulation are the key factors for efficient hyperpolarization through dissolution dynamic nuclear polarization (dissolution-DNP). We provide a comprehensive characterization of the DNP process for Na-[1-(13)C]acetate selected as a model for non-self-glassing agents: the solid-state polarization dynamics of different formulations and the effect of the paramagnetic agent (trityl radical) on the pattern of polarization and the relaxation profile were extensively analyzed. We quantified the effects of the glassing agent and Gd(3+)-chelate on DNP performance.

Enhanced performance large volume dissolution-DNP.

A systematic study of the performance of the dissolution process in dissolution-DNP is presented. A relatively simple set of modifications is made to the standard Hypersense dissolution system to enable polarization of large volume samples. These consist of a large volume sample cup along with supporting modifications to the dissolution head and related components.

Hyperpolarized H2 O MR angiography.

Purpose: The aim of this study was to demonstrate that dissolution- dynamic nuclear polarization is capable of hyperpolarizing water protons and that the signal from the hyperpolarized bolus injection can be exploited in angiographic applications.

Methods: We hyperpolarized water/glycerol using dynamic nuclear polarization followed by dissolution in D2 O.

Results: A water (1) H signal enhancement of 77 times compared with 4.

Formulation and utilization of choline based samples for dissolution dynamic nuclear polarization.

Hyperpolarization by the dissolution dynamic nuclear polarization (DNP) technique permits the generation of high spin polarization of solution state. However, sample formulation for dissolution-DNP is often difficult, as concentration and viscosity must be optimized to yield a dissolved sample with sufficient concentration, while maintaining polarization during the dissolution process. The unique chemical properties of choline permit the generation of highly soluble salts as well as deep eutectic mixtures with carboxylic acids and urea.

Storage of magnetization as singlet order by optimal control designed pulses.

Purpose: The use of hyperpolarization to enhance the sensitivity of MRI has so far been limited by the decay of the polarization through T1 relaxation. Recently, methods have been proposed that extend the lifetime of the hyperpolarization by storing the spin order in slowly relaxing singlet states.

Methods: With this aim, optimal control theory was applied to create pulses that for near-equivalent spins accomplish transfers in and out of the singlet state with maximum efficiency while ensuring robustness toward variations in the nuclear spin system Hamiltonian (chemical shift, J-couplings, B1 and B0 magnetic field inhomogeneity).

Recycling and imaging of nuclear singlet hyperpolarization.

The strong enhancement of NMR signals achieved by hyperpolarization decays, at best, with a time constant of a few minutes. Here, we show that a combination of long-lived singlet states, molecular design, magnetic field cycling, and specific radiofrequency pulse sequences allows repeated observation of the same batch of polarized nuclei over a period of 30 min and more. We report a recycling protocol in which the enhanced nuclear polarization achieved by dissolution-DNP is observed with full intensity and then returned to singlet order.

Assessment of early diabetic renal changes with hyperpolarized [1-(13) C]pyruvate.

Background: This experimental study explores a novel magnetic resonance imaging/spectroscopic (MRI/MRS) method that measures changes in renal metabolism in a diabetic rat model. This hyperpolarized metabolic MRI/MRS method allows monitoring of metabolic processes in seconds by >10 000-fold enhancement of the MR signal. The method has shown that the conversion of pyruvate to bicarbonate, i.

Rapid determination of biosynthetic pathways using fractional isotope enrichment and high-resolution dynamic nuclear polarization enhanced NMR.

Carbon-13 NMR has traditionally been a method of choice for the determination of metabolic pathways. Through fractional labeling, (13)C spectra allow the identification of fragments incorporated as a unit into a biosynthesized molecule. The low sensitivity of (13)C spectroscopy is an impediment to such studies, especially if compounded with an often limited availability of biosynthesized molecules.

Spontaneous emission of NMR signals in hyperpolarized proton spin systems.

Hyperpolarization of nuclear spins is gaining increasing interest as a tool for improving the signal-to-noise ratio of NMR and MRI. While in principle, hyperpolarized samples are amenable to the same or similar experiments as are used in conventional NMR, the large spin polarization may give rise to unexpected effects. Here, spontaneous emission of signal was observed from proton spin systems, which were hyperpolarized to negative spin temperature by dynamic nuclear polarization (DNP).

Applications of dynamic nuclear polarization to the study of reactions and reagents in organic and biomolecular chemistry.

Nuclear Magnetic Resonance (NMR) is an important spectroscopic tool for the identification and structural characterization of molecules in chemistry and biochemistry. The most significant limitation of NMR compared to other spectroscopies is its relatively low sensitivity, which thus often requires long measurement times or large amounts of sample. A way of increasing sensitivity of single scan NMR spectra by several orders of magnitude is through hyperpolarization of nuclear spins.

Rapid sample injection for hyperpolarized NMR spectroscopy.

Due to its ability to enhance the signal of a single NMR scan by several orders of magnitude, solid-to-liquid state dynamic nuclear polarization (DNP) appears well suited for the analysis of minimal amounts of compounds, as well as for the study of rapid chemical reactions. A key requirement in enabling the application of DNP-NMR to typical small-molecule substances encountered in chemistry and biochemistry is the ability to obtain high-resolution spectra, while at the same time minimizing the loss of polarization due to spin relaxation between the separate steps of DNP polarization and NMR measurement. Here, we present data demonstrating the capability of measuring DNP enhanced NMR spectra of compounds with comparably short relaxation times, with only minimal line broadening attributable to the sample transfer process.

Sequentially acquired two-dimensional NMR spectra from hyperpolarized sample.

A scheme capable of acquiring heteronuclear 2D NMR spectra of hyperpolarized sample is described. Hyperpolarization, the preparation of nuclear spins in a polarized state far from thermal equilibrium, can increase the NMR signal by several orders of magnitude. It presents opportunities to apply NMR spectroscopy to dilute samples that would otherwise yield insufficient signal.

Temporal chemical shift correlations in reactions studied by hyperpolarized nuclear magnetic resonance.

High-resolution nuclear magnetic resonance spectroscopy (NMR) has the capability of providing often unrivaled detail on molecular structure and dynamics. Through hyperpolarization, a decisive gain in signal strength can be realized, which extends the applicability of NMR to the investigation of rapid processes far from equilibrium. The progress of irreversible chemical and biochemical reactions can be followed by hyperpolarized NMR with relative ease, within an observable window encompassing the subsecond to second time scales.

Chemical shift correlations from hyperpolarized NMR by off-resonance decoupling.

Nuclear magnetic resonance, through observation of chemical shift, allows the separate identification of each atom in a molecule. Thus, NMR spectra impart an often unrivaled wealth of information on molecular structure. A particular advantage of NMR spectroscopy is the ability to record multidimensional spectra, which provide correlations between atoms.