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

We report synthesis of N-15-3-E-19-pyridine via Zincke salt formation with overall 35% yield and 84% N-15 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 F-19 nucleus in millitesla and microtesla magnetic field regimes in N-15-3-E-19-pyridine and N-14-3-F-19-pyridine. We found the mismatch between N-15 and F-19 magnetic-field hyperpolarization profiles in the microtesla regime indicating that the spontaneous hyperpolarization process likely happens directly from parahydrogen-derived hydride protons to F-19 nucleus without spin-relaying via N-15 site. In the case of SABRE magnetic-field regime (millitesla magnetic-field range), we found that magnetic-field profiles for H-1 and F-19 hyperpolarization are very similar and F-19 polarization levels are significantly lower than H-1 SABRE polarization levels and lower than F-19 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 F-19 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.