Versatile Macrocyclic Platform for the Complexation of [ nat Y/ 90 Y]Yttrium and Lanthanide Ions.

We report a macrocyclic ligand (H 3 L 6 ) based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing three acetate pendant arms and a benzyl group attached to the fourth nitrogen atom of the macrocycle. The X-ray structures of the Y L 6 and Tb L 6 complexes reveal nine coordination of the ligand to the metal ions through the six nitrogen atoms of the macrocycle and three oxygen atoms of the carboxylate pendants. A combination of NMR spectroscopic studies ( 1 H, 13 C, and 89 Y) and DFT calculations indicated that the structure of the Y L 6 complex in the solid state is maintained in an aqueous solution. The detailed study of the emission spectra of the Eu L 6 and Tb L 6 complexes revealed Ln 3+ -centered emission with quantum yields of 7.0 and 60%, respectively. Emission lifetime measurements indicate that the ligand offers good protection of the metal ions from surrounding water molecules, preventing the coordination of water molecules. The Y L 6 complex is remarkably inert with respect to complex dissociation, with a lifetime of 1.7 h in 1 M HCl. On the other hand, complex formation is fast (∼1 min at pH 5.4, 2 × 10 -5 M). Studies using the 90 Y-nuclide confirmed fast radiolabeling since [ 90 Y]Y L 6 is nearly quantitatively formed (radiochemical yield (RCY) > 95) in a short time over a broad range of pH values from ca. 2.4 to 9.0. Challenging experiments in the presence of excess ethylenediaminetetraacetic acid (EDTA) and in human serum revealed good stability of the [ 90 Y]Y L 6 complex. All of these experiments combined suggest the potential application of H 3 L 6 derivatives as Y-based radiopharmaceuticals.