Synthesis and Characterization of Ru(II) Polypyridyl Complexes with 2-(4-Methylbenzoate)-1H-imidazo[4,5-f][1,10]phenantroline Ligand, and Their DNA Binding, Photocleavage, Physico-Chemical Properties, and Cytotoxicity

Abstract

In search for efficient chemotherapeutic agents, we have synthesized a novel MBIP 2-(4-methylbenzoate)-1H-imidazo[4,5-f][1,10]phenantroline and its Ru(II) polypyridyl complexes of the general formula [Ru(N–N)2(L)]2+ (where N–N = phen (1,10-phenanthroline), bpy (2,2ʹ-bipyridine), dmb (4,4ʹ-dimethyl-2,2ʹ-bipyridine), and L = MBIP. All complexes have been characterized by analytical and spectroscopic methods. Physico-chemical properties of the synthesized complexes such as stability and lipophilicity have been studied. Interaction of Ru(II) complexes with calf-thymus DNA (CT-DNA) has been explored by different spectrophotometric methods. Spectral and viscosity data indicate that all the complexes are probably involved in intercalative binding with DNA. These complexes can cleave pBR322 DNA efficiently via oxidative pathway involving singlet oxygen under photoirradiation. The DNA molecular light switch on and off performance of Ru(II) complexes has been studied. According to antimicrobial activity assays the complexes are potential agents against gram positive and gram negative bacteria. In vitro cytotoxicity has been evaluated by MTT assay against HeLa cell lines, being compared to cisplatin. The live cell imaging and lipophilicity results have revealed that the complexes can possibly cross the cell membranes and accumulate in the nucleus. The cellular localization of Ru(II) complexes determined by their lipophilicity can probably affect their anticancer efficacy and mechanism of action.