Thiacalix[4]arene derivatives as radium ionophores: a study on the requirements for Ra2+ extraction

The synthesis and NOE-based structural characterization is described of thiacalix[4]arene tricarboxylic acid (7), thiacalix[4]crown-5 and -6 monocarboxylic acids (2 and 5), and the bis(N-methylsulfonyl)thiacalix[4]crowns-5 and -6 (4a,b). The 226Ra2+ selectivity coefficients, log(K(Ra)ex/K(M)ex), of the new thiacalix[4]arene derivatives are compared directly with those of thiacalix[4]crown-5 and -6 (1a,b), thiacalix[4]crown-5 and -6 dicarboxylic acids (3a,b), and thiacalix[4]arene di- and tetracarboxylic acids (6 and 8). Thiacalix[4]arene dicarboxylic acid (6) already exhibits a high 226Ra2+ selectivity, but this is significantly improved in the case of 3b, having an additional crown-(6-)ether bridge. The covalent combination of a crown ether and carboxylic acid substituents as in the thiacalix[4]arenes 2,3a,b,4a,b, and 5 gives a better 226Ra2+ selectivity in the presence of Sr2+ or Ba2+ than mixtures of dibenzo-21-crown-7 and thiacalix[4]arene dicarboxylic acid (6) or of pentadecanoic acid and thiacalix[4]crown-6 (1b).