DNA binding, nuclease and superoxide scavenging activity studies on mononuclear cobalt complexes derived from tridentate ligands Kaushik Ghosh ⇑ , Varun Mohan, Pramod Kumar, Udai P. Singh Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India article info Article history: Received 16 May 2012 Accepted 16 September 2012 Available online 26 September 2012 Keywords: Cobalt complex Crystal structure Electrochemistry SOD activity DNA binding Nuclease activity abstract A new family of mononuclear cobalt complexes was synthesized using tridentate ligands Pyimpy (Pyimpy = 1-phenyl-1-(pyridin-2-yl)-2-(pyridin-2-ylmethylene)hydrazine) and PampH (PampH = N 0 -phenyl-N 0 -(pyridin-2-yl)picolinohydrazide). The complexes [Co(Pyimpy)Cl 2 ](1a), [Co(Pyimpy) 2 ](ClO 4 ) 2 (1b), [Co(Pamp)Cl 2 ](2a) and [Co(Pamp) 2 ](ClO 4 )(2b) were characterized by elemental analysis, UV–Vis, IR, NMR, ESI-MS spectral studies and conductivity measurements. Molecular structure of 1a was deter- mined by X-ray crystallography. Redox properties of the complexes were examined by cyclic voltamme- try. Superoxide dismutase (SOD) activity of the complexes was assayed by xanthine/xanthine oxidase/ nitroblue tetrazolium assay. We investigated the DNA binding properties of these complexes by absorp- tion spectral, fluorescence quenching and circular dichroism spectral studies. Nuclease activity and their mechanism were also investigated. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction In the recent years there has been considerable interest in the interaction of transition metal complexes with DNA and nuclease activity studies because of their applications in probing structural variations in nucleic acids [1], identifying binding sites of DNA li- gands [2], designing artificial nucleases [3–5] and serving as che- motherapeutic agent in cancer research [6]. In this regard, among the first row transition elements, copper and iron got much atten- tion. Copper possesses high affinity for nucleobases and exhibits biologically accessible redox properties [7]. Iron-bleomycin causes DNA damage and clinically used for cancer treatment [8,9]. Several iron complexes are known to exhibit DNA interaction and nuclease activity [10–13]. On the other-hand cobalt, a constituent of vitamin B 12 and one of the essential elements in biosystem [14] received less attention [15–17]. Cobalt polypyridyl complexes were investi- gated for DNA interaction and nuclease activity studies [18–28] however, reports for oxidative cleavages are few [20,29–33]. In the present study, we have explored the coordination chem- istry of cobalt because it possesses several interesting properties. First, usual oxidation states of +2 and +3 in cobalt complexes give rise to kinetically labile and kinetically inert complexes, respec- tively [34–36]. Second, cobalt(III) is a strong Lewis acid and exhib- its ligand exchange properties. Third, Co(III) has important role in catalytic hydrolysis of phosphate esters [37]. Hettich and cowork- ers reported that Co(III) complexes are known to be most effective catalysts for hydrolytic cleavage of amides, esters and phosphates [38]. Fourth, cobalt ion is present in natural nucleases [36,39–41] or sometimes required for the activity of nucleases [37,42–45]. There are reports that substitution of zinc by cobalt in several nuc- leases may result the enhancement of the enzyme activity [41]. Fifth, DNA cleaving properties of cobalt complexes are sometimes similar to ruthenium complexes [15]. Moreover, antiproliferative activity of the cobalt complexes was determined in MCF-7 and MDA-MB-231 human breast cancer cells and very promising re- sults were obtained [46]. Hence, in the present report we describe the synthesis and characterization of cobalt complexes [Co(Pyimpy)Cl 2 ] (1a), [Co(Pyimpy) 2 ](ClO 4 ) 2 (1b), [Co(Pamp)Cl 2 ](2a), [Co(Pamp) 2 ](ClO 4 ) (2b) derived from the tridentate ligands Pyimpy and PampH (H stands for dissociable proton) which are depicted in Scheme 1 [47]. Both Pyimpy and PampH have two of the three donor centers in common which are pyridine nitrogens, however the third donor is an iminium nitrogen for Pyimpy whereas carboxamido nitrogen for PampH. The complexes were characterized by UV–Vis, IR, and NMR spectral studies. Molecular structure of 1a was determined by X-ray crystallography. Redox property of the complexes was scrutinized and superoxide dismutase activity was examined by xanthine/xanthine oxidase/nitroblue tetrazolium assay. DNA inter- action was investigated by UV–Vis, fluorescence and circular dichroism spectral studies. We have also investigated the nuclease activity of our complexes and results of mechanistic studies will be described in this report. Recently we have reported that the car- boxamido functionality plays a crucial role to impart the DNA cleaving property to the manganese complexes [47]. Moreover zinc 0277-5387/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.poly.2012.09.025 ⇑ Corresponding author. Fax: +91 1332 273560. E-mail address: ghoshfcy@iitr.ernet.in (K. Ghosh). Polyhedron 49 (2013) 167–176 Contents lists available at SciVerse ScienceDirect Polyhedron journal homepage: www.elsevier.com/locate/poly