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Abstract Signal Amplification by Reversible Exchange (SABRE) technique enables nuclear spin hyperpolarization of wide range of compounds using parahydrogen. Here we present the synthetic approach to prepare¹⁵N‐labeled [¹⁵N]dalfampridine (4‐amino[¹⁵N]pyridine) utilized as a drug to reduce the symptoms of multiple sclerosis. The synthesized compound was hyperpolarized using SABRE at microtesla magnetic fields (SABRE‐SHEATH technique) with up to 2.0 %¹⁵N polarization. The 7‐hour‐long activation of SABRE pre‐catalyst [Ir(IMes)(COD)Cl] in the presence of [¹⁵N]dalfampridine can be remedied by the use of pyridine co‐ligand for catalyst activation while retaining the¹⁵N polarization levels of [¹⁵N]dalfampridine. The effects of experimental conditions such as polarization transfer magnetic field, temperature, concentration, parahydrogen flow rate and pressure on¹⁵N polarization levels of free and equatorial catalyst‐bound [¹⁵N]dalfampridine were investigated. Moreover, we studied¹⁵N polarization build‐up and decay at magnetic field of less than 0.04 μT as well as¹⁵N polarization decay at the Earth's magnetic field and at 1.4 T. 

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. 

Abstract NMR hyperpolarization techniques enhance nuclear spin polarization by several orders of magnitude resulting in corresponding sensitivity gains. This enormous sensitivity gain enables new applications ranging from studies of small molecules by using high‐resolution NMR spectroscopy to real‐time metabolic imagingin vivo. Several hyperpolarization techniques exist for hyperpolarization of a large repertoire of nuclear spins, although the¹³C and¹⁵N sites of biocompatible agents are the key targets due to their widespread use in biochemical pathways. Moreover, their longT₁allows hyperpolarized states to be retained 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 the hyperpolarization of¹⁵N nuclei. Although large sensitivity gains are enabled by hyperpolarization,¹⁵N natural abundance is only ∼0.4 %, so isotopic labeling of the molecules to be hyperpolarized is required in order to take full advantage of the hyperpolarized state. Herein, we describe selected advances in the preparation of¹⁵N‐labeled compounds with the primary emphasis on using these compounds for SABRE polarization in microtesla magnetic fields through 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.