Rhenium(i) complexation–dissociation strategy for synthesising fluorine-18 labelled pyridine bidentate radiotracers

Abstract

A novel fluorine-18 method employing rhenium(I) mediation is described herein. The method was found to afford moderate to high radiochemical yields of labelled rhenium(I) complexes. Subsequent thermal dissociation of the complexes enabled the radiosynthesis of fluorine-18 labelled pyridine bidentate structures which could not be radiofluorinated hitherto. This rhenium(I) complexation–dissociation strategy was further applied to the radiosynthesis of [18F]CABS13, an Alzheimer's disease imaging agent, alongside other 2,2′-bipyridine, 1,10-phenanthroline and 8-hydroxyquinoline labelled radiotracers. Computational modelling of the reaction mechanism suggests that the efficiency of rhenium(I) activation may be attributed to both an electron withdrawal effect by the metal center and the formation of an acyl fluoride intermediate which anchors the fluoride subsequent to nucleophilic addition. © The Royal Society of Chemistry 2020 - Open Access