An Electrochemical Study of Antineoplastic Gallium, Iron and Ruthenium Complexes with Redox Noninnocent α-N-Heterocyclic Chalcogensemicarbazones

The electrochemical properties of a series of alpha-N-heterocyclic chalcogensemicarbazones (HL), namely, thiosemicarbazones, selenosemicarbazones, and semicarbazones, and their gallium(III), iron(III), and ruthenium(Ill) complexes with the general formula [ML2][Y] (M = Ga, Fe or Ru; Y = PF6-, NO3-, or FeCl4-) were studied by cyclic voltammetry. The novel compounds were characterized by elemental analysis, a number of spectroscopic methods (NMR, UV-vis, IR), mass spectrometry and by X-ray crystallography. All complexes show several, mostly reversible, redox waves attributable to the reduction of the noninnocent chalcogensemicarbazone ligands at lower potentials (<-0.4 V vs NHE) than the metal-centered iron or ruthenium redox waves (>0 V vs NHE) in organic electrolyte solutions. The cyclic voltammograms of the gallium complexes display at least two consecutive reversible one-electron reduction waves. These reductions are shifted by similar to 0.6 V to lower potentials in the corresponding iron and ruthenium complexes. The electrochemical, chemical, and spectroscopic data indicate that the ligand-centered reduction takes place at the CH3C=N double bond. Quantum chemical calculations on the geometric and electronic structures of 2-acetylpyridine N-4,N-4-dimethylthiosemicarbazone (HLB), the corresponding metal complexes [Ga(L-B)(2)](+) and [FeII(L-B)(2)], and the one-electron reduction product for each of these species support the assignment of the reduction site and elucidate the observed order of the ligand-centered redox potentials, E-1/2([Fe-II(L)(2)]) < E-1/2(HL) < E-1/2([Ga(L)(2)](+)). The influence of water on the redox potentials of the complexes is reported and the physiological relevance of the electrochemical data for cytotoxicity as well as for ribonucleotide reductase inhibitory capacity are discussed.