Recent progress in hyperpolarized 19F NMR in liquids: parahydrogen and beyond

Fluorine-19 nuclear magnetic resonance (19F NMR) is an attractive and widely studied heteronuclear platform due to its high gyromagnetic ratio, wide chemical-shift dispersion, and negligible endogenous background. However, if only the intrinsically low thermal nuclear polarization is available, then, as with any NMR nucleus, 19F still suffers from a high limit of detection. Hyperpolarization addresses this bottleneck and delivers orders-of-magnitude signal enhancements by creating non-Boltzmann nuclear spin populations. Here, we review recent progress in hyperpolarized 19F NMR in liquids, with a primary emphasis on parahydrogen-based techniques, including both hydrogenative PHIP and reversible binding approaches such as SABRE. We discuss how polarization is generated and transferred, and how 19F-specific spin properties and relaxation pathways govern attainable polarization levels and lifetimes. Key determinants—including magnetic-field dependence, scalar-coupling topology, chemical exchange and hydrogenation kinetics, and catalyst/ligand design—are summarized as mechanistic and practical design variables for optimizing performance. We also survey complementary hyperpolarization strategies, including dissolution and Overhauser-effect DNP, CIDNP, and photo-CIDNP, highlighting their scope, strengths, and limitations. Finally, we outline emerging opportunities and design principles for robust, quantitative hyperpolarized 19F NMR protocols that enable sensitive spectroscopy and analysis in complex chemical and biological environments.