Heterogeneous Microtesla SABRE Enhancement of ¹⁵N NMR Signals

Abstract

The hyperpolarization of heteronuclei via Signal Amplification by Reversible Exchange (SABRE) was investigated under conditions of heterogeneous catalysis and microtesla magnetic fields. Immobilization of [IrCl(COD)(IMes)], [IMes = 1,3-bis(2,4,6-trimethylphenyl), imidazole-2-ylidene; COD = cyclooctadiene] catalyst onto silica particles modified with NH2(CH2)3- linkers engenders an effective heterogeneous SABRE (HET-SABRE) catalyst that was used to demonstrate ~102-fold enhancement of 15N NMR signals in pyridine at 9.4 T following parahydrogen bubbling within a magnetic shield. No 15N NMR enhancement was observed from the supernatant liquid following catalyst separation, which along with XPS characterization, supports that the effects result from SABRE under heterogeneous catalytic conditions. The technique can be developed further for producing catalyst-free agents via SABRE with hyperpolarized heteronuclear spins, and thus is promising for biomedical NMR and MRI applications.

Parahydrogen‐Based Hyperpolarization for Biomedicine

“…After pH 2 bubbling inside a magnetic shield, ~100-fold 15 N NMR enhancements (at 9.4 T) were obtained for 15 N-pyridine via SABRE-SHEATH—the first demonstration of SABRE enhancement of heteronuclei under heterogeneous conditions. [99] Finally, using an approach based on phase-transfer catalysis, Iali et al have demonstrated separation of HP agents (with P H up to ~10%) from organic solvents containing the homogeneous catalyst via agent partitioning into an immiscible aqueous phase. [100] While the polarization levels that were achieved with heterogeneous catalysis so far are too low for a biomedical application, the separation of catalyst and substrate is key and likely necessary to bring this emerging technology from benchtop to bedside.…”

Hyperpolarizing Concentrated Metronidazole 15NO2 Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime

“…[49] Moreover,w eh ave recently reported the preparation of pure (i.e.,c atalyst-free) HP metronidazole solutions [36] as well as heterogeneous 15 NS ABRE-SHEATH [50] and 15 NS ABRE-SHEATH HP metronidazole in aqueous media, [51] thereby potentially enabling the preparation of biologically compatible HP MNZ-15 N 3 injectable formulation(s). [49] Moreover,w eh ave recently reported the preparation of pure (i.e.,c atalyst-free) HP metronidazole solutions [36] as well as heterogeneous 15 NS ABRE-SHEATH [50] and 15 NS ABRE-SHEATH HP metronidazole in aqueous media, [51] thereby potentially enabling the preparation of biologically compatible HP MNZ-15 N 3 injectable formulation(s).…”

Signal Amplification by Reversible Exchange (SABRE): From Discovery to Diagnosis

“…Heterogeneous catalysis has been widely applied in PHIP and DNP methods previously. [73] Currently,n either heterogeneous SABRE nor aqueous SABRE delivers polarization levels that are commensurate with biomedical imaging. [72] This enhancement, despite being low,w as shown to be achieved only from the heterogeneous catalysis by comparison to control experiments on the supernatant solution.…”