Toward Nanomolar Multi-Component Analysis by 19 F NMR.

The widespread application of nuclear magnetic resonance (NMR) spectroscopy in detection is currently hampered by its inherently low sensitivity and complications resulting from the undesired signal overlap. Here, we report a detection scheme to address these challenges, where analytes are recognized by 19 F-labeled probes to induce characteristic shifts of 19 F resonances that can be used as "chromatographic" signatures to pin down each low-concentration analyte in complex mixtures. This unique signal transduction mechanism allows detection sensitivity to be enhanced by using massive chemically equivalent 19 F atoms, which was achieved through the proper installation of nonafluoro- tert -butoxy groups on probes of high structural symmetry. It is revealed that the binding of an analyte to the probe can be sensed by as many as 72 chemically equivalent 19 F atoms, allowing the quantification of analytes at nanomolar concentrations to be routinely performed by NMR. Applications on the detection of trace amounts of prohibited drug molecules and water contaminants were demonstrated. The high sensitivity and robust resolving ability of this approach represent a first step toward extending the application of NMR to scenarios that are now governed by chromatographic and mass spectrometry techniques. The detection scheme also makes possible the highly sensitive non-invasive multi-component analysis that is difficult to achieve by other analytical methods.