19F-centred NMR analysis of mono-fluorinated compounds

Addressing limitations of the existing NMR techniques for the structure determination of mono-fluorinated compounds, we have developed methodology that uses F-19 as the focal point of this process. The proposed F-19-centred NMR analysis consists of a complementary set of broadband, phase-sensitive NMR experiments that utilise the substantial sensitivity of F-19 and its far reaching couplings with H-1 and C-13 to obtain a large number of NMR parameters. The assembled H-1, C-13 and F-19 chemical shifts, values of J(HF), J(HH), and J(FC) coupling constants and the size of C-13 induced F-19 isotopic shifts constitute a rich source of information that enables structure elucidation of fluorinated moieties and even complete structures of molecules. Here we introduce the methodology, provide a detailed description of each NMR experiment and illustrate their interpretation using 3-fluoro-3-deoxy-d-glucose. This novel approach performs particularly well in the structure elucidation of fluorinated compounds embedded in complex mixtures, eliminating the need for compound separation or use of standards to confirm the structures. It represents a major contribution towards the analysis of fluorinated agrochemicals and (radio)pharmaceuticals at any point during their lifetime, including preparation, use, biotransformation and biodegradation in the environment. The developed methodology can also assist with the investigations of the stability of fluoroorganics and their pharmacokinetics. Studies of reaction mechanisms using fluorinated molecules as convenient reporters of these processes, will also benefit.

Automated summary

This article introduces a new NMR analysis method centered on F-19, which utilizes a set of broadband, phase-sensitive NMR experiments to obtain a large number of NMR parameters and achieve structure elucidation of fluorinated compounds. The method performs well in the structure determination of fluorinated compounds embedded in complex mixtures.