The coordination chemistry of large metal ions presents fundamental challenges arising from differences in ionic radius, charge, and electronic structure, particularly for heavy p-block and alkaline-earth metals. Herein, we report an experimental and computational investigation of the size-adaptive macrocyclic chelators py-macrodipa and py2-macrodipa with Pb2+, Bi3+, and Ba2+, with Ba2+ employed as a nonradioactive surrogate for Ra2+. Potentiometric and spectrophotometric measurements reveal strong aqueous complexation across all three metals, with stability constants of log K = 14.01(1) and 14.37(4) for Pb2+, 16.74(2) and 17.36(3) for Bi3+, and 7.85(3) and 8.01(5) for Ba2+ with py-macrodipa and py2-macrodipa, respectively. Single-crystal X-ray diffraction, NMR spectroscopy, and density functional theory calculations demonstrate the pronounced conformational flexibility of py-macrodipa and py2-macrodipa. Radiochemical studies show quantitative labeling of 203Pb and 207Bi within 5 min at room temperature at micromolar ligand concentrations, comparable to macropa, while 133Ba is quantitatively labeled with a 10-4 M ligand concentration within 1 h. All complexes remain stable in human serum at 37 °C for up to 5 days. These results demonstrate the potential of py-macrodipa and py2-macrodipa as chelators for 203Pb, 207Bi, and 133Ba, suggesting their potential as alternative diagnostic and therapeutic radionuclides.
Lee et al. (Thu,) studied this question.