Low-micromolar Quantification of Fluorinated Analytes Using Hyperpolarised 19F Benchtop NMR

Benchtop 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. Here we demonstrate 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 via SABRE (Signal Amplification By Reversible Exchange) hyperpolarisation. Further reductions in LOD to (600 ± 20) nM and (17.5 ± 2.0) μM are achieved by combining SABRE with SHARPER (Sensitive, Homogeneous, And Resolved PEaks in Real time) detection. Quantification is demonstrated over the micromolar concentration range using linear external calibration. The effects of polarisation transfer to the solvent via proton exchange in the case of TFBA are shown to be minimised in methanol-d4; however, 19F detection and quantification are also achieved in protio methanol, with a LOD of (42.6 ± 3.6) μM.