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

Abstract

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(III) complexes with the general formula [ML(2)][Y] (M = Ga, Fe or Ru; Y = PF(6)(-), NO(3)(-), or FeCl(4)(-)) 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 approximately 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 CH(3)CN double bond. Quantum chemical calculations on the geometric and electronic structures of 2-acetylpyridine (4)N,(4)N-dimethylthiosemicarbazone (HL(B)), the corresponding metal complexes [Ga(L(B))(2)](+) and [Fe(II)(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.

A Comparative Study of In Vitro Cytotoxic, Antioxidant, and Antimicrobial Activity of Pt(II), Zn(II), Cu(II), and Co(III) Complexes with N‐heteroaromatic Schiff Base (E)‐2‐[N′‐(1‐pyridin‐2‐yl‐ethylidene)hydrazino]acetate

“…Contrary to platinum, copper, and cobalt, zinc is a redox inert metal and does not take part in oxidation‐reduction reactions. However, in binuclear complex 2 , aphaO ligand could transfer electrons via the CN Schiff base double bond, leading to the formation of reactive species capable of attacking cellular targets, as already demonstrated for other Schiff base complexes with redox inert metal centers . Taking into account that in cell‐free system, pro‐oxidant generation of hydroxyl radical reached plateau after 1 h, it is noteworthy that strong correlation with elevated ROS production in leukemic cells was observed.…”

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

“…[8] The mode of action of Fe complexes of α-N-heterocyclic thiosemicarbazones intracellularly is associated with their redox activity. The formal potentials of the reversible Fe III /Fe II redox couple of pyridine TSCs lie within the range of available cellular oxidants and reductants, [8][9][10][11] thus allowing the complexes to undergo redox cycling and thereby produce reactive oxygen species under physiological conditions, which can destroy the tyrosyl radical of RR. [4] Scheme 1.…”

Development of ruthenium-based complexes as anticancer agents: toward a rational design of alternative receptor targets

“…NAMI-A and RAPTA-T seem to be highly effective against metastases, whereas KP1019 showed good activity toward primary tumors. Apart from these compounds, other Ru-based complexes have been synthesized and their potentials as anticancer agents have been evaluated (Grguric-Sipka et al 2003, Hotze et al 2003, Wu et al 2003, 2009, Cabrera et al 2004, Mazumder et al 2004, Brindell et al 2005, Jakupec et al 2005, Waern et al 2005, Deubel and Lau 2006, Romerosa et al 2006, Karki et al 2007, Pascu et al 2007, Schmid et al 2007, Singh et al 2007, Giovagnini et al 2008, Herman et al 2008, Kowol et al 2008, Rajendiran et al 2008, Vrábel et al 2008, Camm et al 2009, Corral et al 2009, Helena et al 2009, Kandioller et al 2009, Mendoza-Ferri et al 2009, Fetzer et al 2011, Kamatchi et al 2012, Loughrey et al 2012. At present, NAMI-A-and RAPTA-based compounds are still the best alternatives for further derivatization.…”