Low‐Micromolar Quantification of Fluorinated Analytes Using Hyperpolarized 19F Benchtop Nuclear Magnetic Resonance

Limits of detection and quantification of fluorinated analytes by ¹⁹F benchtop (1 T) NMR spectroscopy in the high nanomolar to low micromolar range are achieved using signal amplification by reversible exchange (SABRE) combined with the multiplet-refocusing technique, SHARPER (Sensitive, Homogeneous, And Resolved PEaks in Real time).

Benchtop nuclear magneic resonance (NMR) spectrometers are more affordable and accessible than high-field NMR instruments but suffer from higher limits of detection (LOD) and lower chemical shift resolution due to their moderate magnetic fields. Herein, reductions in the single-scan LOD values for ¹⁹F benchtop (1 T) NMR of 3,5-difluoropyridine (DFP) and 2,4,6-trifluorobenzylamine (TFBA) to (6.84 ± 0.45) μM and (162 ± 28) μM are demonstrated via signal amplification by reversible exchange (SABRE) hyperpolarization. Further reductions in LOD to (600 ± 20) nM and (17.5 ± 2.0) μM are achieved by combining SABRE with sensitive, homogeneous, and resolved peaks in real time detection. Quantification is demonstrated over the micromolar concentration range using linear external calibration. The effects of polarization transfer to the solvent via proton exchange in the case of TFBA are shown to be minimized in methanol-d ₄; however, ¹⁹F detection and quantification are also achieved in protio methanol, with a LOD of (42.6 ± 3.6) μM.

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