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 Flabeled probes to induce characteristic shifts of 19 F resonances that can be used as "chromatographic" signatures to pin down each lowconcentration 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 nonafluorotert-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.

Nuclear magnetic resonance (NMR) is an indispensable tool for structural elucidation and noninvasive analysis. Automated identification of analytes with NMR is highly pursued in metabolism research and disease diagnosis; however, this process is often complicated by the signal overlap and the sample matrix. We herein report a detection scheme based on 19 F NMR spectroscopy and dynamic recognition, which effectively simplifies the detection signal and mitigates the influence of the matrix on the detection. It is demonstrated that this approach can not only detect and differentiate capsaicin and dihydrocapsaicin in complex realworld samples but also quantify the ibuprofen content in sustainedrelease capsules. Based on the 19 F signals obtained in the detection using a set of three 19 F probes, automated analyte identification is achieved, effectively reducing the odds of misrecognition caused by structural similarity.