Expanding the Molecular Scope of Photo-CIDNP for Nanomolar ¹⁹ F NMR Detection of Amines

Enhancing NMR sensitivity is essential for broadening its utility in metabolic profiling and other biological analyses. Photochemically induced dynamic nuclear polarization (photo-CIDNP) provides NMR signal enhancement at mild conditions, but its applicability has remained largely restricted to a small subset of intrinsically photo-CIDNP-active molecules. Here, we introduce a derivatization-based strategy to expand the molecular scope of photo-CIDNP. Guided by theoretical calculations, we designed a photo-CIDNP ¹⁹F probe that selectively reacts with amines. As a proof of concept, we show that all proteinogenic amino acids except proline can be derivatized to yield strongly hyperpolarized ¹⁹F NMR signals, with signal enhancements of up to 160-fold. The method enables single-scan detection of total amino acids at 1.0 μM and individual amino acids at concentrations as low as 20 nM, and it allows rapid, quantitative profiling of amino acids in complex cell lysates. This work provides a generalizable blueprint for molecular design of photo-CIDNP probes and substantially expands the analytical capabilities of this hyperpolarization technique.