Synthesis and Anticancer Activity of Long-Chain Isonicotinic Ester Ligand-Containing Arene Ruthenium Complexes and Nanoparticles

Arene ruthenium complexes containing long-chain <i>N</i>-ligands L¹ = NC⁵H⁴–4-COO–C⁶H⁴–4-O–(CH²)⁹–CH³ or L² = NC⁵H⁴–4-COO–(CH²)¹⁰–O–C⁶H⁴–4-COO–C⁶H⁴–4-C⁶H⁴–4-CN derived from isonicotinic acid, of the type [(arene)Ru(L)Cl²] (arene = C⁶H⁶, L = L¹: <b>1</b>; arene = <i>p</i>-MeC⁶H⁴Pr ^<i>i</i> , L = L¹: <b>2</b>; arene = C⁶Me⁶, L = L¹: <b>3</b>; arene = C⁶H⁶, L = L²: <b>4</b>; arene = <i>p</i>-MeC⁶H⁴Pr ^<i>i</i> , L = L²: <b>5</b>; arene = C⁶Me⁶, L = L²: <b>6</b>) have been synthesized from the corresponding [(arene)RuCl²]² precursor with the long-chain <i>N</i>-ligand L in dichloromethane. Ruthenium nanoparticles stabilized by L¹ have been prepared by the solvent-free reduction of <b>1</b> with hydrogen or by reducing [(arene)Ru(H²O)³]SO⁴ in ethanol in the presence of L¹ with hydrogen. These complexes and nanoparticles show a high anticancer activity towards human ovarian cell lines, the highest cytotoxicity being obtained for complex <b>2</b> (IC⁵⁰ = 2 μM for A2780 and 7 μM for A2780cisR).