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.

Structural and biological studies of mononuclear metal (II) complexes containing hetero ligand based on 3‐acetylpyridine thiosemicarbazone

“…Upon complexation of the ligand with Palladium (II) and Nickel (II) ions, the signal peaks position of the thioamide N(4′)H 2 and hydrazinic N(2′)H were shifted from (8.05 and 9.85) ppm in ligand to (8.70 and 13.2) and (9.12 and 10.86) ppm in case of palladium and nickel complexes, respectively. The shift to a higher frequency for the protons of the acetyl group attached to the azomethine carbon atom, (CH 3 )–C=N, in complexes further confirms the coordination of the ligand to the metal centers via the azomethine nitrogen 62,63,65 . 1 H NMR spectrum of [Pd(3‐APT)Cl 2 ] and [Ni(3‐APT) 2 ]Cl 2 .H 2 O are seen in Figure S2a,b.…”

Structural and biological studies of mononuclear metal (II) complexes containing hetero ligand based on 3‐acetylpyridine thiosemicarbazone

“…Upon complexation of the ligand with Palladium (II) and Nickel (II) ions, the signal peaks position of the thioamide N(4′)H 2 and hydrazinic N(2′)H were shifted from (8.05 and 9.85) ppm in ligand to (8.70 and 13.2) and (9.12 and 10.86) ppm in case of palladium and nickel complexes, respectively. The shift to a higher frequency for the protons of the acetyl group attached to the azomethine carbon atom, (CH 3 )–C=N, in complexes further confirms the coordination of the ligand to the metal centers via the azomethine nitrogen 62,63,65 . 1 H NMR spectrum of [Pd(3‐APT)Cl 2 ] and [Ni(3‐APT) 2 ]Cl 2 .H 2 O are seen in Figure S2a,b.…”

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.…”

Ternary Phenolate-Based Thiosemicarbazone Complexes of Copper(II): Magnetostructural Properties, Spectroscopic Features and Marked Selective Antiproliferative Activity against Cancer Cells

“…The X-ray crystal structure is depicted in Figure 2 while selected bond distances and angles are presented in Table 2. The distance of the Schiff-base bond C=N [C(15)-N(1) = 1.2904 (19) Å] lies within the range observed for normal imine bonds [1.26-1.30 Å] [ [13][14][15]19,20,[60][61][62][63][64][65][66][67][68][69] in non-coordinated ligands. Upon reduction in the Schiff base, the imine double bond becomes a single bond (C-N) with a distance of ~1.47 Å [65].…”

“…The distance of the Schiff-base bond C=N [C(15)-N(1) = 1.2904 (19) Å] lies within the range observed for normal imine bonds [1.26-1.30 Å] [ [13][14][15]19,20,[60][61][62][63][64][65][66][67][68][69] in non-coordinated ligands. Upon reduction in the Schiff base, the imine double bond becomes a single bond (C-N) with a distance of ~1.47 Å [65]. The C(16)-S(1) distance of 1.7029( 14) Å verifies the occurrence of the thione tautomer.…”

Structural and biological studies of mononuclear metal (II) complexes containing hetero ligand based on 3‐acetylpyridine thiosemicarbazone

“…Upon complexation of the ligand with Palladium (II) and Nickel (II) ions, the signal peaks position of the thioamide N(4′)H 2 and hydrazinic N(2′)H were shifted from (8.05 and 9.85) ppm in ligand to (8.70 and 13.2) and (9.12 and 10.86) ppm in case of palladium and nickel complexes, respectively. The shift to a higher frequency for the protons of the acetyl group attached to the azomethine carbon atom, (CH 3 )–C=N, in complexes further confirms the coordination of the ligand to the metal centers via the azomethine nitrogen 62,63,65 . 1 H NMR spectrum of [Pd(3‐APT)Cl 2 ] and [Ni(3‐APT) 2 ]Cl 2 .H 2 O are seen in Figure S2a,b.…”

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.…”

Ternary Phenolate-Based Thiosemicarbazone Complexes of Copper(II): Magnetostructural Properties, Spectroscopic Features and Marked Selective Antiproliferative Activity against Cancer Cells

“…The X-ray crystal structure is depicted in Figure 2 while selected bond distances and angles are presented in Table 2. The distance of the Schiff-base bond C=N [C(15)-N(1) = 1.2904 (19) Å] lies within the range observed for normal imine bonds [1.26-1.30 Å] [ [13][14][15]19,20,[60][61][62][63][64][65][66][67][68][69] in non-coordinated ligands. Upon reduction in the Schiff base, the imine double bond becomes a single bond (C-N) with a distance of ~1.47 Å [65].…”

“…The distance of the Schiff-base bond C=N [C(15)-N(1) = 1.2904 (19) Å] lies within the range observed for normal imine bonds [1.26-1.30 Å] [ [13][14][15]19,20,[60][61][62][63][64][65][66][67][68][69] in non-coordinated ligands. Upon reduction in the Schiff base, the imine double bond becomes a single bond (C-N) with a distance of ~1.47 Å [65]. The C(16)-S(1) distance of 1.7029( 14) Å verifies the occurrence of the thione tautomer.…”

Structural and biological studies of mononuclear metal (II) complexes containing hetero ligand based on 3‐acetylpyridine thiosemicarbazone

“…Upon complexation of the ligand with Palladium (II) and Nickel (II) ions, the signal peaks position of the thioamide N(4′)H 2 and hydrazinic N(2′)H were shifted from (8.05 and 9.85) ppm in ligand to (8.70 and 13.2) and (9.12 and 10.86) ppm in case of palladium and nickel complexes, respectively. The shift to a higher frequency for the protons of the acetyl group attached to the azomethine carbon atom, (CH 3 )–C=N, in complexes further confirms the coordination of the ligand to the metal centers via the azomethine nitrogen 62,63,65 . 1 H NMR spectrum of [Pd(3‐APT)Cl 2 ] and [Ni(3‐APT) 2 ]Cl 2 .H 2 O are seen in Figure S2a,b.…”

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.…”

Ternary Phenolate-Based Thiosemicarbazone Complexes of Copper(II): Magnetostructural Properties, Spectroscopic Features and Marked Selective Antiproliferative Activity against Cancer Cells

“…The X-ray crystal structure is depicted in Figure 2 while selected bond distances and angles are presented in Table 2. The distance of the Schiff-base bond C=N [C(15)-N(1) = 1.2904 (19) Å] lies within the range observed for normal imine bonds [1.26-1.30 Å] [ [13][14][15]19,20,[60][61][62][63][64][65][66][67][68][69] in non-coordinated ligands. Upon reduction in the Schiff base, the imine double bond becomes a single bond (C-N) with a distance of ~1.47 Å [65].…”

“…The distance of the Schiff-base bond C=N [C(15)-N(1) = 1.2904 (19) Å] lies within the range observed for normal imine bonds [1.26-1.30 Å] [ [13][14][15]19,20,[60][61][62][63][64][65][66][67][68][69] in non-coordinated ligands. Upon reduction in the Schiff base, the imine double bond becomes a single bond (C-N) with a distance of ~1.47 Å [65]. The C(16)-S(1) distance of 1.7029( 14) Å verifies the occurrence of the thione tautomer.…”