Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange

Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available para-hydrogen as a hyperpolarization source. SABRE can hyperpolarize protons and heteronuclei. Here we focus on the heteronuclear variant introduced as SABRE-SHEATH (SABRE in SHield Enables Alignment Transfer to Heteronuclei) and nitrogen-15 targets in particular. We show that ¹⁵N-SABRE works more efficiently and on a wider range of substrates than ¹H-SABRE, greatly generalizing the SABRE approach. In addition, we show that nitrogen-15 offers significantly extended T₁ times of up to 12 minutes. Long T₁ times enable higher hyperpolarization levels but also hold the promise of hyperpolarized molecular imaging for several tens of minutes. Detailed characterization and optimization are presented, leading to nitrogen-15 polarization levels in excess of 10% on several compounds.