Heteroleptic bis(benzazole) ruthenium complexes: structural characterization, DNA/BSA binding, and anticancer studies

Abstract

The reactions of 2,6-bis(benzimidazol-2-yl)pyridine (HL1) and 2,6-bis(benzothiazol-2-yl)pyridine (HL2) with RuCl3.3H2O afforded complexes [Ru(L1)Cl3] (Ru1) and [Ru(L2)Cl3] (Ru2), respectively. Subsequent treatment of complex Ru1 with DMSO led to the generation of the cationic heteroleptic Ru(II) complex [Ru(L1)(DMSO)2(Cl)] (Ru3). Separately, reactions of complexes Ru1 or Ru2 with 2,2′-bipyridine (bpy) and 1,10-phenanthroline (phen) co-ligands led to the isolation of the heteroleptic Ru(II) complexes [Ru(L1)(bpy)(Cl)] (Ru4), [Ru(L2)(bpy)(Cl)]Cl (Ru5), and [Ru(L2)(phen)(Cl)]Cl (Ru6) in moderate yields. Solid structure of complex Ru3 established a tridentate coordination mode of L1, in which two DMSO and one chloro co-ligands complete the octahedral geometry. DNA binding studies of complexes Ru1 and Ru3–Ru6 indicated groove-binding interactions accompanied by partial intercalation, with complexes Ru4 and Ru6 showing the highest binding affinities. The bovine serum albumin (BSA) protein interaction occurred via a static quenching mechanism, as evidenced from the quenching constants (Kq) in the order of 1011 M−1. The biological potency of the ruthenium complexes was studied using Caco-2 and MCF-7 cancer cell lines and normal cell lines HeK293 and KMST-6. Complex Ru1 demonstrated moderate cytotoxicity and selectivity against MCF-7 cancer cell line (IC50 of 12.30 μM and SI of 4.74), while the heteroleptic ruthenium complexes Ru3 - Ru6 displayed very low biological activities.