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

The electrochemical properties of a series of α-N-heterocyclic
chalcogensemicarbazones (HL), namely, thiosemicarbazones, selenosemicarbazones,
and semicarbazones, and their gallium(III), iron(III), and ruthenium(III)
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 ∼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 4N,4N-dimethylthiosemicarbazone (HLB), the corresponding
metal complexes [Ga(LB)2]+ and [FeII(LB)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, E1/2([FeII(L)2]) < E1/2(HL) < E1/2([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.