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 = Me-3-tacn, BzMe(2)-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 Bu-n) 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 (F-19, Al-27, Ga-71 and In-115) NMR spectroscopic studies, leading to sharp resonances with F-19-Ga-71 and F-19-In-115 couplings evident. The [MF3(L)] are extremely stable in aqueous solution and at low pH; they crystallise as tetrahydrates, [MF3(Me-3-tacn)]center dot 4H(2)O, with extended H-bonding networks formed through both F center dot center dot center dot H-O and O center dot center dot center dot H-O contacts. [InF3(BzMe(2)-tacn)]center dot 1.2H(2)O also shows intermolecular F center dot center dot center dot 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(BzMe(2)-tacn)] is effected readily at room temperature in aqueous MeCN over 30-60 min on addition of 2.99 mol equiv. of [F-19]-KFaq and 0.4 mL [F-18]-KFaq (100-500 MBq) to [GaCl3(BzMe(2)-tacn)] with ca. 30% incorporation.