Synthesis of Ru(ii) cyclometallated complexes via C(aryl)–S bond activation: X-ray structure, DNA/BSA protein binding and antiproliferative activity

Abstract

As a contribution to the development of new ruthenium complexes with pharmacologically interesting properties, two new cyclometallated ruthenium(II) carbonyl complexes of the general formula [Ru(L¹/L²)(CO)(PPh₃)₂] (1/2) were synthesized and characterized using analytical and spectral techniques (IR, UV/visible, ¹H NMR and ESI-MS). The crystal structures of complexes (1 and 2) were confirmed by X-ray crystallography, which indicated CNO tridentate coordination of the ligands through C(aryl)–S bond activation. The electronic structures and spectral properties of complexes 1 and 2 were interpreted by DFT and TDDFT calculations. The binding ability of the Ru(II) complexes with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) has been explored by absorption and emission titration methods. A good binding affinity with DNA was observed with an intercalative binding mode, which was further confirmed by EB displacement and viscosity measurement studies. The BSA protein binding studies have been monitored by quenching of tryptophan and tyrosine residues in the presence of complexes and the quenching mechanism was found to be static. Synchronous and 3D fluorescence spectroscopy studies were carried out to validate the micro environmental changes in BSA. In addition, the in vitro cytotoxicity of the ligands and complexes against the human breast cancer cell line (MCF-7), human lung cancer cell line (A549), triple negative breast cancer cell line (MDA-MB-231) and gastric adenocarcinoma cell line (AGS) was investigated by using the MTT assay and the IC₅₀ values of the complexes towards MCF-7 cell lines were found to be even less compared to cisplatin.