Original article Synthesis and DNA-binding studies of two ruthenium(II) complexes of an intercalating ligand D. Lawrence Arockiasamy, S. Radhika, R. Parthasarathi, Balachandran Unni Nair * Chemical Laboratory, Central Leather Research Institute, Council of Scientific and Industrial Research, Chennai 600 020, India article info Article history: Received 11 January 2008 Received in revised form 5 June 2008 Accepted 9 October 2008 Available online 1 November 2008 Keywords: Ruthenium(II) complexes DNA Polypyridyl Photocleavage Ethidium bromide abstract Two new ruthenium(II) complexes [Ru(bpy) 2 (HBT)] 2þ (1) and [Ru(phen) 2 (HBT)] 2þ (2) (bpy ¼ 2,2 0 - bipyridine; phen ¼ 1,10-phenanthroline; HBT ¼ 11H, 13H-4, 5,9,10,12,14-hexaaza-benzo [b] triphenylene) have been synthesized and characterized by elemental analysis, mass spectra, 1 H NMR and cyclic vol- tammetry. The DNA binding property of the two complexes has been investigated employing absorption spectroscopy, fluorescence spectroscopy and viscosity measurements. Both complexes 1 and 2 have been found to prefer intercalative binding to DNA. The DNA binding constants for the two complexes have been measured to be 5.71  0.20  10 7 and 4.65  0.20  10 7 M 1 through ethidium bromide displace- ment method. Molecular modeling studies too indicate that both complexes 1 and 2 prefer intercalative binding to DNA and both these complexes exhibit similar DNA binding energies. Both complexes 1 and 2 bring about photocleavage of plasmid DNA when irradiated at 440 nm. Ó 2008 Elsevier Masson SAS. All rights reserved. 1. Introduction Studies on the interaction of transition metal complexes with DNA continue to attract the attention of researchers due to their importance in design and development of synthetic restriction enzymes, chemotherapeutic drugs and DNA foot printing agents [1–8]. In this respect ruthenium(II) complexes have attracted a great deal of attention due to their unique spectroscopic and electrochemical properties [9–18]. Ruthenium polypyridyl complexes have received special attention due to their strong metal to ligand charge transfer (MLCT) absorption, their unique emission characteristics, the perturbance of which could be exploited to study their DNA binding properties [19–27]. Despite a considerable amount of literature on metal complex–DNA interaction, the knowledge of the nature of binding of these complexes to DNA and their binding geometries has remained a subject of intense debate. The binding mode of [Ru(phen) 3 ] 3þ remains as an issue of rigorous debate [28,29]. On the other hand there is a consensus about intercalative binding of complexes such as [Ru(bpy) 2 (dppz)] 2þ and [Ru(phen) 2 (dppz)] 2þ (dppz ¼ dipyrido[3,2-a:2 0 ,3 0 -c]-phenazine) to DNA. In these two complexes dppz ligand has been shown to intercalate between the base pairs of double helical DNA [30–35]. It has also been realized that the molecule can intercalate either through the major groove or through the minor groove due to small modifications in the intercalating ligand. The complex [Ru(phen) 2 (dppz)] 2þ has been shown to intercalate into the major groove of double helix DNA [36,37] while [Ru(phen) 2 (dpq)] 2þ (dpq ¼ dipyrido[3,2-d:2 0 ,3 0 -f]quinoxaline) intercalates preferen- tially into the minor groove of DNA [38,39]. Ever since the report of the DNA base mismatch recognition agent, [Ru(bpy) 2 (chrysi)] 3þ (chrysi ¼ 5,6-chrysenequinone dii- mine), there has been renewed interest in the synthesis of mixed ligand complexes of ruthenium. The complex [Ru(bpy) 2 (chrysi)] 3þ has been found to bind at the mismatch sites in DNA specifically and upon photoactivation cleaves the DNA backbone neighbouring the site [40]. The source of preferential binding has been reported to be the sterically bulky chrysi intercalating ligand, which is too wide to intercalate readily in to B-form DNA, but binds the desta- bilized regions associated with base mismatches [41]. In our labo- ratory, we have initiated a systematic study to understand the role of ancillary ligands in the DNA binding mode of mixed ligand complexes of ruthenium(II) and to develop base mismatch recog- nition agent [42]. In this communication, we describe the synthesis and DNA binding properties of two new ruthenium(II) mixed ligand complexes. Abbreviations: Bpy, 2,2-bipyridine; Phen, 1,10-phenanthroline; HBT, 11H, 13H-4, 5,9,10,12,14-Hexaaza-benzo [b] triphenylene; dppz, dipyrido[3,2-a:2 0 ,3 0 -c]-phena- zine; dpq, dipyrido[3,2-d:2 0 ,3 0 -f]quinoxaline; chrysi, 5,6-chrysenequinone diimine; tris, tris(hydroxymethyl) aminomethane; CT, calf thymus; DMSO, dimethyl sulf- oxide; DIP, 4,7-diphenyl-1,10-phenanthroline; DMHBT, 11,13-dimethyl-4, 5,9,10,12,14-hexaaza-benzo [b] triphenylene-10,12-dione. * Corresponding author. Tel.: þ91 44 2441 1630; fax: þ91 44 2491 1589. E-mail address: bunair@clri.info (B.U. Nair). Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech 0223-5234/$ – see front matter Ó 2008 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.ejmech.2008.10.013 European Journal of Medicinal Chemistry 44 (2009) 2044–2051