Order-Unity 13 C Nuclear Polarization of [1-13 C]Pyruvate in Seconds and the Interplay of Water and SABRE Enhancement

Abstract

Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) is investigated to achieve rapid hyperpolarization of ¹³ C₁ 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 H₂ 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 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 CD₃ 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 T₁ 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.

Keywords: 13C; NMR spectroscopy; hyperpolarization; parahydrogen; pyruvate.