¹⁹ F-Labeled Probes for Recognition-Enabled Chromatographic ¹⁹ F NMR

The NMR technique is among the most powerful analytical methods for molecular structural elucidation, process monitoring, and mechanistic investigations; however, the direct analysis of complex real-world samples is often hampered by crowded NMR spectra that are difficult to interpret. The combination of fluorine chemistry and supramolecular interactions leads to a unique detection method named recognition-enabled chromatographic (REC) ¹⁹ F NMR, where interactions between analytes and ¹⁹ F-labeled probes are transduced into chromatogram-like ¹⁹ F NMR signals of discrete chemical shifts. In this account, we summarize our endeavor to develop novel ¹⁹ F-labeled probes tailored for separation-free multicomponent analysis. The strategies to achieve chiral discrimination, sensitivity enhancement, and automated analyte identification will be covered. The account will also provide a detailed discussion of the underlying principles for the design of molecular probes for REC ¹⁹ F NMR where appropriate.