Synthesis, structure, solution behavior, reactivity and biological evaluation of oxidovanadium(iv/v) thiosemicarbazone complexes

Abstract

The synthesis and characterization of an oxidovanadium(iv) [VIVO(L)(acac)] (1) and of two dioxidovanadium(v) [VVO2(L')] (2) and [VVO2(L)] (2a) complexes of the Schiff base formed from the reaction of 4-(p-fluorophenyl) thiosemicarbazone with pyridine-2-aldehyde (HL) are described. The oxidovanadium(iv) species [VIVO(L)(acac)] (1) was synthesized by the reaction of VIVO(acac)2 with the thiosemicarbazone HL in refluxing ethanol. The recrystallization of [VIVO(L)(acac)] (1) in DMF, CH3CN or EtOH gave the same product i.e. the dioxidovanadium(v) complex [VVO2(L)] (2a); however, upon recrystallization of 1 in DMSO a distinct compound [VVO2(L')] (2) was formed, wherein the original ligand L- is transformed to a rearranged one, L'-. In the presence of DMSO the ligand in complex 1 is found to undergo methylation at the carbon centre attached to imine nitrogen (aldimine) and transformed to the corresponding VVO2-species through in situ reaction. The synthesized HL and the metal complexes were characterized by elemental analysis, IR, UV-Vis, NMR and EPR spectroscopy. The molecular structure of [VVO2(L')] (2) was determined by single crystal X-ray crystallography. The methylation of various other ligands and complexes prepared from different vanadium precursors under similar reaction conditions was also attempted and it was confirmed that the imine methylation observed is both ligand and metal precursor specific. Complexes 1 and 2 show in vitro insulin-like activity against insulin responsive L6 myoblast cells, higher than VIVO(acac)2, with complex 1 being more potent. In addition, the in vitro cytotoxicity studies of HL, and of complexes 1 and 2 against the MCF-7 and Vero cell lines were also done. The ligand is not cytotoxic and complex 2 is significantly more cytotoxic than 1. DAPI staining experiments indicate that an increase in the time of incubation and an increase of concentration of the complexes lead to the increase in cell death.

Water-Soluble Dioxidovanadium(V) Complexes of Aroylhydrazones: DNA/BSA Interactions, Hydrophobicity, and Cell-Selective Anticancer Potential

“…From this graph it is evident that an increase in hydrophobicity correlates with a steady increase in cytotoxicity for all three cell lines. These results suggest that hydrophobic character, a property that eases the ability to cross the cellular membrane, leading to better availability of compounds in its target, may be useful to the maximum cellular uptake of oxidovanadium complexes and the associated cytotoxic effects. − The reasons for the complex ability for cell permeation through the lipid layer of the cell membrane may be attributed to the coordination behavior, the polarity of the ligand, and the reduced central metal ion through charge equilibration. ,,,,− …”

“…With the above findings and as part of our ongoing research on oxidovanadium(IV/V), 29−32,35,59,65−69 non-oxido vanadium(IV), 29,70−72 and cis-dioxidovanadium(V) 33,34,36 complexes, with systems having pharmacological relevance, 29,[31][32][33][34]36,68,69 in this work the synthesis of a series of water-soluble anionic dioxidovanadium(V) complexes with aroylhydrazone ligands involving alkali metals (Na + , K + , and Cs + ) as countercations is described. In previous work, 36 a related series of alkali-metal dioxidovanadium(V) complexes exhibited poor cytotoxicity against HeLa cells: thus herein, a modified ligand system has been employed through the introduction of heterocyclic rings, as compounds with heterocycles in the ligand system have been found to be the most cytotoxic, 36 and the cytotoxicity of these complexes against several cancer cell lines, including HeLa, has been explored.…”

Mo(VI) Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations

“…The cytotoxic potential of the complexes 1 – 4 was determined against the above cell lines through a conventional MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] inspection. ,,, Briefly, after the cells attained 80% confluency, the cells were seeded in a 96-well plate at a concentration of 5 × 10 4 cells per well. These cells were then treated for a period of 48 h, with different concentrations of each complex that were initially dissolved in DMSO and further diluted in DMEM media.…”

“…The status of nuclear disintegration in cancerous cells in response to complex treatment was examined by staining with DAPI. ,,, HeLa and HT-29 cells were treated with IC 50 concentration of the complexes. Complexes were not added to cells for control group experiment.…”

Synthesis, characterization, DFT calculations and anticancer activity of a new oxidovanadium(iv) complex with a ligand derived from o-vanillin and thiophene

“…38 However, some dioxidovanadium(V) complexes with thiosemicarbazones shows variable IC 50 (range 15-90 µM) on MCF7 cells. 39 Compared with complexes of the same ligand and other metals, tested in our laboratory ,…”