Spin–Lattice Relaxation of Hyperpolarized Metronidazole in Signal Amplification by Reversible Exchange in Micro-Tesla Fields

Simultaneous reversible chemical exchange of para -hydrogen and to-be-hyperpolarized substrate on metal centers enables spontaneous transfer of spin order from para -hydrogen singlet to nuclear spins of the substrate. When performed at a sub-micro-tesla magnetic field, this technique of NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). SABRE-SHEATH has been shown to hyperpolarize nitrogen-15 sites of a wide range of biologically interesting molecules to a high polarization level ( P > 20%) in 1 min. Here, we report on a systematic study of 1 H, 13 C, and 15 N spin–lattice relaxation ( T 1 ) of metronidazole- 13 C 2 - 15 N 2 in the SABRE-SHEATH hyperpolarization process. In the micro-tesla range, we find that all 1 H, 13 C, and 15 N spins studied share approximately the same T 1 values (ca. 4 s under the conditions studied) because of mixing of their Zeeman levels, which is consistent with the model of relayed SABRE-SHEATH effect. These T 1 values are significantly lower than those at a higher magnetic field (i.e. the Earth’s magnetic field and above), which exceed 3 min in some cases. Moreover, these relatively short T 1 values observed below 1 μT limit the polarization build-up process of SABRE-SHEATH, thereby limiting the maximum attainable 15 N polarization. The relatively short T 1 values observed below 1 μT are primarily caused by intermolecular interactions with quadrupolar iridium centers or dihydride protons of the employed polarization transfer catalyst, whereas intramolecular spin–spin interactions with 14 N quadrupolar centers have a significantly smaller contribution. The presented experimental results and their analysis will be beneficial for more rational design of SABRE-SHEATH (i) polarization transfer catalysts and (ii) hyperpolarized molecular probes in the context of biomedical imaging and other applications.