Synthesis, structure, DNA binding and photocleavage activity of a ruthenium(II) complex with 11-(9-acridinyl)dipyrido[3,2-a:2′,3′-c]phenazine ligand

Abstract

In our search for new DNA intercalating ligands, a novel bifunctional intercalator 11-(9-acridinyl)dipyrido[3,2-a:2′,3′-c]phenazine, acdppz (has two potentially effective intercalators via dipyridophenazine(dppz) and acridine which are linked together via C–C bond) and its corresponding Ru(II) polypyridyl complex [Ru(phen)2(acdppz)]2+ (where phen=1,10-phenanthroline) have been synthesized and characterized. The electrochemical behaviors of the ligand and its complex have been thoroughly examined. The structure of acdppz and [Ru(phen)2(acdppz)]2+ were determined by X-ray crystallography. From the crystal structure of the complex, we found that the dppz moiety is not coplanar with the acridine ring, having a dihedral angle of 64.79 in the acdppz. The selected bond lengths and angles for the crystal structure of [Ru(phen)2(acdppz)]2+ were compared to the geometry-optimized molecular structure of [Ru(phen)2(acdppz)]2+ derived by Gaussian. The interaction of [Ru(phen)2(acdppz)]2+ with calf-thymus (CT) DNA was investigated by absorption and viscometry titration, thermal denaturation studies. The above measurements indicated that the complex binds less strongly with the CT DNA due to the intercalation by the ruthenium bound acdppz with an intrinsic binding constant of 2.6×105M−1. Molecular-modeling studies also support an intercalative mode of binding of the complex to the model duplex d(CGCAATTGCG)2 possibly from the major groove with a slight preference for GC rich region. Additionally, the title complex promotes the cleavage of plasmid pBR322 DNA upon irradiation under aerobic conditions.