Comparative interaction of thyroxine and analogues with Cu(II)

Thyroxine and analogues form complexes with Cu(II) with extremely high stability constants. The Cu(II)-catalyzed oxidation of ascorbic acid was used to study the interaction of these ligands with Cu(II). Additional spectral evidence for these interactions was also presented. In the thyronine series, thyroxine is the most effective Cu(II) complexer except for O-methyl thyroxine. The lack of requirement of the free phenol is also shown by the high activity of the benzyl ether of 3,5-diiodotyrosine. Modification of the alanine side chain, either blocking or removing the amino groups, results in a marked decrease of Cu(II) complexing ability. No amino acid, except where a third group capable of interaction with Cu(II) is present, is effective in the same concentration range as the diiodothyronines or diphenyl ethers. Other metal ions were tested and none appear to be able to compete with Cu(II) for thyroxine. It is concluded that the carboxyl and the amino group of thyroxine are definitely involved in the Cu(II)-thyroxine type of chelate. The prime ring and the diphenyl ether structures also contribute stability to these complexes with Cu(II), but a free phenol group is not required. Possible specific structures of the Cu(II)-thyroxine and related chelates are discussed.