Chelation of heavy group 2 (radio)metals by p-tert-butylcalix[4]arene-1,3-crown-6 and logK determination via NMR

A crown-bridged calix[4]arene scaffold was investigated as lead compound for the ligation of heavy alkaline earth metals such as strontium and barium, which appear to be useful for radiopharmaceutical applications in diagnosis as well as in radiotherapy. In particular barium, due to its chemical similarities, could serve as a surrogate for radium, a metal of high radiopharmaceutical interest. The ability of p-tert-butylcalix[4]arene-1,3-crown-6 (1) in particular to chelate cations, such as group 1 and 2 metal ions or ammonium ions is well known. Also, the manifold possibilities of structural modification on the upper- and lower-rim as well as on the crown itself produce properties that may lead to a highly selective and effective chelating agent. In this work, titration experiments of the perchlorate salts of Ba²⁺, Sr²⁺ and Pb²⁺ with ligand 1 were performed to determine their stability constants (logK = 4.7, 4.3, and 3.3, respectively) by ¹H NMR measurements in acetonitrile-d₃.