Reversible Parahydrogen Induced Hyperpolarization of 15N in Unmodified Amino Acids Unraveled at High Magnetic Field

• Published in: Advanced science 2023-08, Vol.10 (23), p.n/a
• Main Authors: Vaneeckhaute, Ewoud, Tyburn, Jean‐Max, Kempf, James G., Martens, Johan A., Breynaert, Eric
• Format: Article
• Language: English
• Subjects: 15N‐NMR; Amino acids; Ammonia; Binding sites; Catalysis; hydrides; Hydrogenation; hyperpolarization; isotopologues; Ligands; Magnetic fields; Nitrogen; NMR; Nuclear magnetic resonance; parahydrogen; SABRE hyperpolarization
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202207112

Amino acids (AAs) and ammonia are metabolic markers essential for nitrogen metabolism and cell regulation in both plants and humans. NMR provides interesting opportunities to investigate these metabolic pathways, yet lacks sensitivity, especially in case of 15N. In this study, spin order embedded in p‐H2 is used to produce on‐demand reversible hyperpolarization in 15N of pristine alanine and ammonia under ambient protic conditions directly in the NMR spectrometer. This is made possible by designing a mixed‐ligand Ir‐catalyst, selectively ligating the amino group of AA by exploiting ammonia as a strongly competitive co‐ligand and preventing deactivation of Ir by bidentate ligation of AA. The stereoisomerism of the catalyst complexes is determined by hydride fingerprinting using 1H/D scrambling of the associated N‐functional groups on the catalyst (i.e., isotopological fingerprinting), and unravelled by 2D‐ZQ‐NMR. Monitoring the transfer of spin order from p‐H2 to 15N nuclei of ligated and free alanine and ammonia targets using SABRE‐INEPT with variable exchange delays pinpoints the monodentate elucidated catalyst complexes to be most SABRE active. Also RF‐spin locking (SABRE‐SLIC) enables transfer of hyperpolarization to 15N. The presented high‐field approach can be a valuable alternative to SABRE‐SHEATH techniques since the obtained catalytic insights (stereochemistry and kinetics) will remain valid at ultra‐low magnetic fields. Reversible hyperpolarization of 15N in amino acids is achieved using an iridium catalyst and parahydrogen. Ammonia competes with alanine to circumvent spontaneous deactivation of the catalyst. Hyperpolarized 15N NMR demonstrates reversible exchange of alanine on the SABRE catalyst, while hydride fingerprinting reveals its stereoisomerism.