¹⁹F Hyperpolarization of ¹⁵N-3-¹⁹F-Pyridine via Signal Amplification by Reversible Exchange

We report synthesis of ¹⁵N-3-¹⁹F-pyridine via Zincke salt formation with overall 35% yield and 84% ¹⁵N isotopic purity. Hyperpolarization studies of signal amplification by reversible exchange (SABRE) and SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) were performed to investigate the mechanism of polarization transfer from parahydrogen-derived hydride protons to ¹⁹F nucleus in millitesla and microtesla magnetic-field regimes in ¹⁵N-3-¹⁹F-pyridine and ¹⁴N-3-¹⁹F-pyridine. We found the mismatch between ¹⁵N and ¹⁹F magnetic-field hyperpolarization profiles in the microtesla regime indicating that the spontaneous hyperpolarization process likely happens directly from parahydrogen-derived hydride protons to ¹⁹F nucleus without spin-relaying via ¹⁵N site. In the case of SABRE magnetic-field regime (millitesla magnetic-field range), we found that magnetic-field profiles for ¹H and ¹⁹F hyperpolarization are very similar and ¹⁹F polarization levels are significantly lower than ¹H SABRE polarization levels and lower than ¹⁹F SABRE-SHEATH (i.e., obtained at microtesla magnetic field) polarization levels. Our findings support the hypothesis that in millitesla magnetic-field regime, the process of ¹⁹F nuclei hyperpolarization is relayed via protons of the substrate and therefore is very inefficient. These findings are important in the context of improvement of the hyperpolarization hardware and rational design of the hyperpolarized molecular probes.