Comparative Solution Equilibrium Study of the Interactions of Copper(II), Iron(II) and Zinc(II) with Triapine (3-Aminopyridine-2-carbaldehyde Thiosemicarbazone) and Related Ligands

The interactions of Cu-II, Zn-II and Fe-II with Triapine (3-aminopyridine-2-carbaldehyde thiosemicarbazone), which is currently undergoing phase II clinical trials as a chemotherapeutic antitumour agent, were investigated in a water/DMSO mixture. The proton-dissociation constants of the ligands, the stability constants and the coordination modes of the metal complexes formed were determined by pH-potentiometric, UV/Vis spectrophotometric, EPR, H-1 NMR spectroscopic and ESI-MS methods. Two N-terminally dimethylated derivatives of Triapine were also studied. Mono- and bis-ligand complexes in different protonation states were identified. Furthermore, the formation of the dinuclear species [Cu2L3](+) was confirmed for all ligands by EPR spectroscopy and ESI-MS measurements. The results showed that the N-terminally dimethylated ligands are much more potent chelators than Triapine for the divalent metal ions studied. All three ligands formed the least stable complexes with Zn-II, whereas the Fen complexes were somewhat more stable than the corresponding Cu-II species.