“Direct” 13C Hyperpolarization of 13C‐Acetate by MicroTesla NMR Signal Amplification by Reversible Exchange (SABRE)

• Published in: Angewandte Chemie International Edition 2020-01, Vol.59 (1), p.418-423
• Main Authors: Gemeinhardt, Max E., Limbach, Miranda N., Gebhardt, Thomas R., Eriksson, Clark W., Eriksson, Shannon L., Lindale, Jacob R., Goodson, Elysia A., Warren, Warren S., Chekmenev, Eduard Y., Goodson, Boyd M.
• Format: Article
• Language: English
• Subjects: acetate; Acetic acid; Amplification; Biomedical materials; Bubbling; Catalysts; Exchanging; heteronuclei; Hyperpolarization; Imidazole; Magnetic fields; Magnetic resonance imaging; Metabolism; Metabolites; NMR; Nuclear magnetic resonance; parahydrogen; Pyridines; SABRE-SHEATH; Sheaths; Sodium; Substrates
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201910506

Herein, we demonstrate “direct” 13C hyperpolarization of 13C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐13C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the 13C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of “direct” transfer of spin order from parahydrogen to 13C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the 13C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism. Give it to me straight: Addition of metabolically relevant 13C‐acetate and parahydrogen to solutions containing activated catalyst gives rise to enhancement of 13C NMR signals by up to ≈100‐fold at 9.4 T. The hyper‐polarization is shown to proceed directly, unlike previous efforts that have required either synthesis of catalyst‐binding composite structures, and/or the indirect relay of spin order through other species.