Toward a new avenue in ruthenium-sulphur chemistry of binuclear μ-sulphido bridged (μ-S)2 complexes having Ru2S2 core: Targeted synthesis, crystal structure, biomolecules interaction and their in vitro anticancer activities

Abstract

A series of hybrid thiosemicarbazone derivatives (H2L1–3) were synthesized by the reactions of diacetyl-2-(4-methyl-3-thiosemicarbazone) with hydrazine derivatives such as 2-hydrazinoquinoline, 2-hydrazinobenzothiazole and 6-hydrazinonicotinic acid arm. The resulting hybrid diacetyl-2-(4-methyl-3-thiosemicarbazonato-hydrazine derivatives were successfully employed as tetradentate ligands to react with [RuHClCO(PPh3)3]. The reactions have led to the binuclear organo-ruthenium(II) complexes of the core type [Ru2(Ln)2(CO)2(μ-S)2], (n=1–3) in which the ruthenium(II) ion bridged by sulphur atoms (μ-S)2. In the new complexes, the ligand charge and stoichiometry proportions could be controlled by the addition of base. All the compounds have been characterized by IR, UV–vis, ESI-MS, (1H, 13C) NMR spectra and elemental analyses. The crystal structure of complexes 1, 2 has been determined by X-ray crystallography, which confirmed the coordination mode of the ligands and revealed a distorted octahedral geometry around the ruthenium ion. Natural bond orbital calculations of complexes 1 and 2 showed that the majority of the electron density of donors tends to the ruthenium ion, since the calculated Mulliken charge for the ruthenium ion is much lesser than the formal value. The binding mode of these complexes with biomolecules such as calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) protein have been investigated by diverse spectrophotometric methods and the results revealed an intercalative mode of interaction. Furthermore, the bio-catalytic efficiencies such as catecholase and phosphatase like activities of ruthenium complexes exhibited high rate (kcat) constant. Furthermore, the complexes (1–3) displayed more cytotoxicity against anticancer cell lines such as MCF-7 (breast), A549 (lung), and HepG2 (liver) than normal Vero cell line. The less cytotoxic activity towards normal cell lines showed that they affect only cancer cell lines. The antiproliferative efficacy of complexes (1–3) has also been analyzed using morphological staining properties (AO/EB, DAPI) by fluorescence microscopy visualization.