A comparative evaluation of calix[4]arene-1,3-crown-6 as a ligand for selected divalent cations of radiopharmaceutical interest

Radionuclides of divalent metals like lead-203, lead-212 and the radionuclides of alkaline earth metals barium-131 and strontium 89 are promising candidates for a radiopharmaceutical application. In addition, the heavy homologues radium-223 and radium-224 – with similar properties to barium - are suitable alpha-emitters for the targeted alpha-particle therapy. However, there is a lack of suitable chelation agents, especially for heavy group 2 metals. The macrocycle calix[4]arene-1,3-crown-6 seems to strongly interact with these metals. Therefore, this ligand and its coordination to the divalent cations of barium, strontium, and lead have been investigated. The complex formation was analyzed by NMR and UV/Vis titration experiments in acetonitrile, and stability constants were determine with both methods. It was found that the stability of these complexes increase in the order of strontium, barium, and lead. Additional to these investigations, X-ray crystallography, solvent-dependent ¹H-NMR, and ²⁰⁷Pb NMR measurements were performed to deliver a deeper insight into the coordination chemistry of this ligand.