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Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) is investigated to achieve rapid hyperpolarization of (13)C(1) spins of [1-(13)C]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 H(2)O. Order-unity (13)C (>50%) polarization of catalyst-bound [1-(13)C]pyruvate is achieved in less than 30 s by restricting the chemical exchange of [1-(13)C]pyruvate at lower temperatures. On the catalyst bound pyruvate, 39% polarization are measured using 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 CD(3)OD. Efficient (13)C polarization is also enabled by favorable relaxation dynamics in sub-microtesla magnetic fields, as indicated by fast polarization buildup rates compared to the T(1) spin-relaxation rates (e.g., ~0.2 s(−1) versus ~0.1 s(−1), respectively, for a 6 mM catalyst-[1-(13)C]pyruvate sample). Finally, the catalyst-bound hyperpolarized [1-(13)C]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-(13)C]pyruvate produced via comparatively fast and simple SABRE-SHEATH-based approaches.

NMR hyperpolarization techniques enhance nuclear spin polarization by several orders of magnitude resulting in corresponding sensitivity gains. This massive sensitivity gain enables new applications ranging from studies of small molecules using high-resolution NMR spectroscopy to real-time metabolic imaging in vivo. Several hyperpolarization techniques exist for hyperpolarization of a large repertoire of nuclear spins, although (13)C- and (15)N- sites of biocompatible agents are the key targets due to their widespread in biochemical pathways. Moreover, their long T(1) allows retaining hyperpolarized states for up to tens of minutes. Signal Amplification by Reversible Exchange (SABRE) is a low-cost and ultrafast hyperpolarization technique that has been shown to be versatile for hyperpolarization of (15)N nuclei. While large sensitivity gains are enabled by hyperpolarization, (15)N natural abundance is only ~0.4%, so that isotopic labeling of the to-be-hyperpolarized molecules is required in order to take full advantage of the hyperpolarized state. Here, we describe selected advances in the preparation of (15)N-labeled compounds with the primary emphasis on using these compounds for their SABRE polarization in microtesla magnetic fields via spontaneous polarization transfer from parahydrogen. Also, these principles can certainly be applied for hyperpolarization of these emerging contrast agents using Dynamic Nuclear Polarization and other techniques.

(15)N spin-lattice relaxation dynamics in metronidazole-(15)N(3) and metronidazole-(15)N(2) isotopologues are studied for rational design of (15)N-enriched biomolecules for Signal Amplification by Reversible Exchange in microtesla fields. (15)N relaxation dynamics mapping reveals the deleterious effects of interactions with polarization transfer catalyst and quadrupolar (14)N nucleus within the spin-relayed (15)N-(15)N network.

Anisomeles indica (L.) kuntze is widely used in folk medicine against various disorders including allergy, sores, inflammation, and fever. This research investigated the antinociceptive, anxiolytic and sedative effects of A. indica methanol extract. The antinociceptive activity was assessed with the acetic acid-induced writhing test and formalin-induced flicking test while sedative effects with open field and hole cross tests and anxiolytic effects with elevated plus maze (EPM) and thiopental-induced sleeping time tests were assayed. Computer aided (pass prediction, docking) analyses were undertaken to find out the best-fit phytoconstituent of total 14 isolated compounds of this plant for aforesaid effects. Acetic acid treated mice taking different concentrations of extract (50, 100, and 200 mg/kg, intraperitoneal) displayed reduced the writhing number. In the formalin-induced test, extract minimized the paw licking time of mice during the first phase and the second phase significantly. The open field and hole-cross tests were noticed with a dose-dependent reduction of locomotor activity. The EPM test demonstrated an increase of time spent percentage in open arms. Methanol extract potentiated the effect of thiopental-induced hypnosis in lesser extent comparing with Diazepam. The results may account for the use of A. indica as an alternative treatment of antinociception and neuropharmacological abnormalities with further intensive studies. The compound, 3,4-dihydroxybenzoic acid was found to be most effective in computer aided models.