Abstract
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 (1)H, (13)C and (15)N spin-lattice relaxation (T(1)) of metronidazole-(13)C(2)-(15)N(2) in SABRE-SHEATH hyperpolarization process. In 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 at the conditions studied) due to 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 higher magnetic (i.e. the Earth's magnetic field and above), which exceed 3 minutes in some cases. Moreover, these relatively short T(1) values observed below 1 micro-Tesla limit the polarization build-up process of SABRE-SHEATH- thereby, limiting maximum attainable (15)N polarization. The relatively short nature of T(1) 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 (14)N 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.