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

Simultaneous reversible chemical exchange of parahydrogen and to-be-hyperpolarized substrate on metal centers enables spontaneous transfer of spin order from parahydrogen singlet to nuclear spins of the substrate. When performed at 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 one minute. Here, we report on a systematic study of ¹H, ¹³C and ¹⁵N spin-lattice relaxation (T₁) of metronidazole-¹³C₂-¹⁵N₂ in SABRE-SHEATH hyperpolarization process. In micro-Tesla range, we find that all ¹H, ¹³C and ¹⁵N spins studied share approximately the same T₁ values (ca. 4 s at the conditions studied) due to mixing of their Zeeman levels, which is consistent with the model of relayed SABRE-SHEATH effect. These T₁ values are significantly lower than those at higher magnetic (i.e. the Earth's magnetic field and above), which exceed 3 minutes in some cases. Moreover, these relatively short T₁ values observed below 1 micro-Tesla limit the polarization build-up process of SABRE-SHEATH- thereby, limiting maximum attainable ¹⁵N polarization. The relatively short nature of T₁ values observed below 1 micro-Tesla is primarily caused by intermolecular interactions with quadrupolar iridium centers or dihydride protons of the employed polarization transfer catalyst, whereas intramolecular spin-spin interactions with ¹⁴N quadrupolar centers have significantly smaller contribution. The presented experimental results and their analysis will be beneficial for more rational design of SABRE-SHEATH (i) polarization transfer catalyst, and (ii) hyperpolarized molecular probes in the context of biomedical imaging and other applications.