Ruthenium(II) bipyridine complexes: from synthesis and crystal structures to electrochemical and cytotoxicity investigation

Abstract

<p>Complexes <b>1–4</b>, [Ru(L)(bpy)₂]PF₆, where bpy = 2,2′-bipyridine; HL = 3-methylpyridine-2-carboxylic acid (<b>HL1</b>), 6-methylpyridine-2-carboxylic acid (<b>HL2</b>), 5-bromopyridine-2-carboxylic acid (<b>HL3</b>) and 6-bromopyridine-2-carboxylic acid (<b>HL4</b>), were synthesized and characterized. The electrochemical character of the complexes was investigated by cyclic voltammetry revealing two reversible reduction waves in the negative range of potentials, most likely due to a reduction of the bipyridine moiety. Cytotoxicity studies by MTT assay for 72 h of drug action revealed that <b>2–4</b> exhibited moderate activity in cervical human tumor cells (HeLa). Complex <b>2</b> exhibited low activity in colon cancer LS-174 cells (180 ± 10), while all complexes were devoid of activity in lung cancer A549 and non-tumor MRC-5 cells, up to 200 μM. Combinational studies of the most active complex <b>2</b>, with pharmacological modulators of cell redox status, L-buthionine-sulfoximine (L-BSO) or N-acetyl-L-cysteine (NAC), showed that when L-BSO potentiated, <b>2</b> induced a sub-G1 peak of the cell cycle in the HeLa cell line. UV–vis and cyclic voltammetry were performed in order to investigate the binding mode of <b>2</b> to DNA and suggested intercalation for the complex–DNA interaction.</p