Modified Calix[4]crowns as Molecular Receptors for Barium

A series of modified calix[4]crown-6 derivatives was synthesized to chelate the heavy group 2 metal barium, which serves as non-radioactive surrogate for radium-223/-224; radionuclides with promising properties for radiopharmaceutical use. These calixcrowns were functionalized either with cyclic amide moieties or proton-ionizable groups and the corresponding barium complexes were synthesized. Stability constants of these complexes were measured using NMR and UV/Vis titration techniques to determine logK values between 4.1 and 6.4. Further extraction studies were performed to characterize the binding affinity of calixcrowns to radioactive barium-133. Additionally, the ligands containing cyclic amides were investigated regarding their barriers for rotation using temperature dependent NMR measurements.