Synthesis of a half-sandwich complex of ruthenium(ii) with a nonsymmetric bis-nitrogen donor ligand: biological investigations

Herein, a new Ru(II)-arene complex [(p-cymene)RuCl(bpyNO)]Cl, 1, bearing 5-methyl-[2,20-bipyrimidine]-1-N-oxide (bpyNO, B) as a nitrogen donor ligand, has been prepared by reaction of [(p-cymene)RuCl(m-Cl)]2, A, and bpyNO. The complex 1 was characterized by means of NMR spectroscopy, HR ESI-Mass, and X-ray crystallography techniques. The optical characteristics of these compounds in the ground state were investigated, and the findings were corroborated by calculations using density functional theory (DFT) and time-dependent DFT (TD-DFT). It was determined by a number of different approaches that every compound had suitable stability in biological media. On several different human cancer cell lines, including lung (A549), breast (MCF7), and cervical (HeLa) cells, and a normal cell line, lung fibroblasts (MRC5), the cytotoxic activities of A, B, 1, and another Ru(II) complex [(p-cymene)RuCl(bpy)]Cl, 2, bpy = 2,20-bipyridine, were tested. Complex 1 demonstrated good to moderate anti-cancer activity. The effect of 1 on the proliferation of the non-tumorigenic cell line, MRC5, was more selective than that of cisplatin in distinguishing cancerous and non-cancerous cell lines. Furthermore, the most cytotoxic complex, 1, induces apoptosis, which causes cell death in the MCF-7 cancer cell line. Electrophoresis mobility shift assay and molecular docking were also performed in order to determine how and in which orientation these Ru(II) complexes are able to bind to DNA.