Exploring transition metal fluoride chelates – synthesis, properties and prospects towards potential PET probes

Abstract

The coordination chemistry of the first row transition metal trifluorides with terpy (2,2′:6′,2′′-terpyridine) and Me₃-tacn (1,4,7-trimethyl-1,4,7-triazacyclononane) was explored to identify potential systems for ¹⁸F radiolabelling. The complexes [MF₃(L)] (M = Cr, Mn, Fe, Co; L = Me₃-tacn, terpy) were synthesised and fully characterised by UV-vis and IR spectroscopy, microanalysis, and, for the diamagnetic [CoF₃(L)], using ¹H, ¹⁹F{¹H} and ⁵⁹Co NMR spectroscopy. Single crystal X-ray analyses are reported for [MF₃(Me₃-tacn)] (M = Mn, Co), [FeF₃(terpy)] and [FeF₃(BnMe₂-tacn)]. Stability tests on [MF₃(Me₃-tacn)] (M = Cr, Mn, Fe) and [M′F₃(terpy)] (M′ = Cr, Fe) were performed and Cl/¹⁹F halide exchange reactions on [CrCl₃(Me₃-tacn)] using [Me₄N]F in anhydrous MeCN solution, and [FeCl₃(Me₃-tacn)] using [Me₄N]F in anhydrous MeCN or KF in aqueous MeCN solution were also carried out. Halide exchange reactions proved to be successful in forming [FeF₃(Me₃-tacn)] in aqueous MeCN solution within 30 minutes. Based upon the clean Cl/F exchange and the good stability observed for [FeF₃(Me₃-tacn)] in a range of competitive media, this was identified as a possible candidate for radiolabelling. ¹⁸F/¹⁹F isotopic exchange was achieved by addition of [¹⁸F]F⁻ in the cyclotron target water to a MeCN solution of the benzyl-substituted analogue, [FeF₃(BnMe₂-tacn)], at a range of concentrations down to 24 nM with heating to 80 °C for 10 min.; the resulting [Fe¹⁸F¹⁹F₂(BnMe₂-tacn)] shows radiochemical purity (RCP) ≥90% after 2 h in a range of formulations, including 10% EtOH/phosphate buffered saline (PBS) and 10% EtOH/human serum albumin (HSA). This is the first reported complex with a transition metal directly bonded to [¹⁸F]F⁻.