Triaza-macrocyclic complexes of aluminium, gallium and indium halides: fast 18F and 19F incorporation via halide exchange under mild conditions in aqueous solution

Abstract

Rapid and complete fluorination of the complexes [MCl₃(L)] (L = Me₃-tacn, BzMe₂-tacn, M = Al, Ga, In) occurs at room temperature via reaction of a MeCN solution of the complex with 3 mol equiv. of KF in water. The Ga and In complexes are also readily fluorinated using R₄NF (R = Me or ⁿBu) in MeCN solution, whereas no reaction occurs with the Al species under these conditions. The distorted octahedral fac-trifluoride coordination at M is confirmed in solution by multinuclear (¹⁹F, ²⁷Al, ⁷¹Ga and ¹¹⁵In) NMR spectroscopic studies, leading to sharp resonances with ¹⁹F–⁷¹Ga and ¹⁹F–¹¹⁵In couplings evident. The [MF₃(L)] are extremely stable in aqueous solution and at low pH; they crystallise as tetrahydrates, [MF₃(Me₃-tacn)]·4H₂O, with extended H-bonding networks formed through both F⋯H–O and O⋯H–O contacts. [InF₃(BzMe₂-tacn)]·1.2H₂O also shows intermolecular F⋯H–O hydrogen bonding contacts. The prospects for developing this coordination chemistry further to take advantage of the high metal–fluoride bond energies to enable rapid, late-stage fluorination of large macromolecules under mild conditions for PET imaging applications in nuclear medicine are discussed. This work also demonstrates that F-18 radiolabelling to form [F-18] [GaF₃(BzMe₂-tacn)] is effected readily at room temperature in aqueous MeCN over 30–60 min on addition of 2.99 mol equiv. of [¹⁹F]–KF_aq and 0.4 mL [¹⁸F]–KF_aq (100–500 MBq) to [GaCl₃(BzMe₂-tacn)] with ca. 30% incorporation.