A research team from the Innovation Academy for Precision Measurement Science and Technology of the Chinese Academy of Sciences has developed a novel theoretical framework to elucidate the structure-activity relationship between molecular structures and polarization properties, and unveiled new strategies for expanding the application of photochemically induced dynamic nuclear polarization (photo-CIDNP) technology in complex biological systems.

The findings were recently published in Journal of the American Chemical Society.

Nuclear magnetic resonance (NMR) is essential for life science and chemical research due to its non-destructive, quantitative and structural analysis advantages, but its wide application has long been limited by low sensitivity. Photo-CIDNP technology can greatly enhance NMR signals through mild reversible photochemical reactions and shows potential in biological research. However, it still faces major challenges, such as a narrow range of polarizable substrates and an unclear relationship between molecular structure and polarization properties.

To address these gaps, the team integrated theoretical calculations with experimental validation. They identified that the polarization efficiency of fluorine-19 (¹⁹F) in fluorine-containing homologues can be effectively predicted by its spin density at the corresponding free radical sites. This finding provides a theoretical foundation for the efficient screening of photo-CIDNP-responsive molecules.

Building on this discovery, the researchers designed and synthesized ¹⁹F probes that are both photo-CIDNP-responsive and highly sensitive for amine-containing compounds. Under single-sampling conditions (just two seconds), the probe enabled rapid detection of a 1 μM amino acid mixture, with signal enhancement typically exceeding 100-fold. It achieved a limit of detection as low as 20 nM (64 scans) for individual amino acids and has been successfully applied to the rapid detection of amine-containing compounds in cell lysates.

By regulating the derivatization unit, the researchers also achieved selective detection of specific amino acids, demonstrating scalability. Leveraging this method, the team further captured the dynamic changes in amino acid levels during cellular oxidative stress, offering new insights into this critical biological process.

This study was supported by funding from the Chinese Academy of Sciences, the Ministry of Science and Technology, and other institutional grants.