HISTAMINE H-2 ANTAGONISTS - POWERFUL LIGANDS FOR COPPER(II) - REINTERPRETATION OF THE FAMOTIDIN-COPPER(II) SYSTEM

Potentiometric, absorption, EPR and C-13 NMR spectroscopic studies per formed for a series of effective H-2, antagonists of histamine (imidaz ole-4-ethanamine) including effective antiulcer drug famotidine, have shown that all ligands containing a guanidine-thiazole fragment co-ord inate copper(II) ions at pH around 2 using two nitrogen donors. The gu anidine moiety having acidic nitrogen (log K 1.5-3.0) acts as an ancho r and the thiazole nitrogens with protonation constants around pK 6.7 very efficiently form a chelate ring. The adjacent thioether sulfur ma y also be involved in metal-ion binding, contributing to the stabiliti es of the complexes formed. At higher pH an amine terminal fragment is involved in co-ordination via one of its nitrogens leading to a {N,N, S,N} binding set. Comparison of all results obtained for the seven com pounds studied strongly suggests that only equimolar species can be de tected in this system. This allows a convincing reinterpretation of ea rlier studies on the copper(II)-famotidine system.