Delivering strong ^sup 1^H nuclear hyperpolarization levels and long magnetic lifetimes through signal amplification by reversible exchange

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 16; p. E3188
• Main Authors: Rayner, Peter J, Burns, Michael J, Olaru, Alexandra M, Norcott, Philip, Fekete, Marianna, Green, Gary G R, Highton, Louise A R, Mewis, Ryan E, Duckett, Simon B
• Format: Journal Article
• Language: English
• Published: Washington National Academy of Sciences 18.04.2017
• Subjects: Biochemistry; Catalysts; Detection times; Drugs; Hyperpolarization; Magnetic resonance imaging; Magnetism; NMR; Nuclear magnetic resonance; Optimization; Polarization; Pyrazine; Pyridazines
• ISSN: 0027-8424; 1091-6490

Hyperpolarization turns typically weak NMR and MRI responses into strong signals so that ordinarily impractical measurements become possible. The potential to revolutionize analytical NMR and clinical diagnosis through this approach reflect this area's most compelling outcomes. Methods to optimize the low-cost parahydrogen-based approach signal amplification by reversible exchange with studies on a series of biologically relevant nicotinamides and methyl nicotinates are detailed. These procedures involve specific ^sup 2^H labeling in both the agent and catalyst and achieve polarization lifetimes of ca. 2 min with 50% polarization in the case of methyl-4,6-d^sub 2^-nicotinate. Because a 1.5-T hospital scanner has an effective ^sup 1^H polarization level of just 0.0005% this strategy should result in compressed detection times for chemically discerning measurements that probe disease. To demonstrate this technique's generality, we exemplify further studies on a range of pyridazine, pyrimidine, pyrazine, and isonicotinamide analogs that feature as building blocks in biochemistry and many disease-treating drugs.