Quasi-Resonance Fluorine-19 Signal Amplification by Reversible Exchange

We report on an extension of the quasi-resonance (QUASR) pulse sequence used for signal amplification by reversible exchange (SABRE), showing that we may target distantly J-coupled ¹⁹F-spins. Polarization transfer from the parahydrogen-derived hydrides to the ¹⁹F nucleus is accomplished via weak five-bond J-couplings using a shaped QUASR radio frequency pulse at a 0.05 T magnetic field. The net result is the direct generation of hyperpolarized ¹⁹F z-magnetization, derived from the parahydrogen singlet order. An accumulation of ¹⁹F polarization on the free ligand is achieved with subsequent repetition of this pulse sequence. The hyperpolarized ¹⁹F signal exhibits clear dependence on the pulse length, irradiation frequency, and delay time in a manner similar to that reported for ¹⁵N QUASR-SABRE. Moreover, the hyperpolarized ¹⁹F signals of 3-¹⁹F-¹⁴N-pyridine and 3-¹⁹F-¹⁵N-pyridine isotopologues are similar, suggesting that (i) polarization transfer via QUASR-SABRE is irrespective of the nitrogen isotopologue and (ii) the presence or absence of the spin-1/2 ¹⁵N nucleus has no impact on the efficiency of QUASR-SABRE polarization transfer. Although optimization of polarization transfer efficiency to ¹⁹F (P ≈ 0.1%) was not the goal of this study, we show that high-field SABRE can be efficient and broadly applicable for direct hyperpolarization of ¹⁹F spins.