19F-Labeled Probes for Recognition-Enabled Chromatographic 19F 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) F-19 NMR, where interactions between analytes and F-19-labeled probes are transduced into chromatogram-like F-19 NMR signals of discrete chemical shifts. In this account, we summarize our endeavor to develop novel F-19-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 F-19 NMR where appropriate.