Triaza-macrocyclic complexes of aluminium, gallium and indium halides: fast 18F and 19F incorporation via halide exchange under mild conditions in aqueous solution†
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]–KFaq and 0.4 mL [18F]–KFaq (100–500 MBq) to [GaCl3(BzMe2-tacn)] with ca. 30% incorporation.