Magneto-structural correlation, antioxidant, DNA interaction and growth inhibition activities of new chloro-bridged phenolate complexes† Perumal Gurumoorthy, a Dharmasivam Mahendiran, a Durai Prabhu, b Chinnasamy Arulvasu b and Aziz Kalilur Rahiman * a A new class of chloro-bridged dinuclear nickel(II) and copper(II) phenolate complexes (1–8) were synthesized from 4-substituted-2-((2-(piperazin-1-yl)ethylimino)methyl)phenols (L 14 ) and characterized. The XRD analysis of complexes 4 and 8 shows two mononuclear units connected through a bridged chlorine atom that gives dinuclear complexes. The stability of the complexes has been determined using a spectrophotometric method. Complexes 5–8 possess significant antioxidant activity against the DPPH radical. The binding studies of complexes with CT-DNA suggest partial intercalative/electrostatic interaction and the cleavage ability for pBR322 DNA shows the involvement of the hydroxyl radical as an intermediate in the cleavage reaction. The IC 50 value of complexes 2, 6 and 8 against the HepG2 cell line is comparable with that of cisplatin. To find the extent of nuclear chromatin cleavage, propidium iodide staining and comet assays were employed. Among the newly synthesized complexes, copper(II) complexes exhibited superior biological activity when compared to their nickel(II) analogues. Introduction DNA is a store and carrier of genetic information in a cell and it is the primary intracellular target of anticancer drugs. The interaction between the small molecules and DNA can cause DNA damage, blocking the division of cancer cells, and result- ing in cell death. 1 The DNA cleavage is an enzymatic reaction which comprises various biological processes as well as biotechnological manipulation of genetic material. Nowadays, exploring and designing novel molecules capable of interacting with DNA, and triggering apoptosis is one of the strategies for researchers to discover effective DNA-targeted anticancer drugs for chemotherapy. 2 In modern medicinal eld, widely and effectively used anti- tumor drugs are Pt-based cisplatin [cis-diamminedichloro platinum(II)], carboplatin [cis-diammine(cyclobutane-1,1-di carboxylato-O,O 0 )platinum(II)], and oxaliplatin [((1R,2R)-cyclo hexane-1,2-diamine)(ethanedioato-O,O 0 )platinum(II)], but they possess inherent limitations such as ototoxicity, nephrotoxicity, peripheral neuropathy and neurotoxicity, nausea, myeolotoxicity, and tumor resistance. 3 Hence, the efforts to mitigate the drawbacks have prompted researchers to develop other transition metal-based drugs. In this connection, attempts are being made to replace these drugs with more efficacious, less toxic, and target specic non-covalently DNA binding (intercalation, groove binding and external static elec- tronic effects) chemotherapeutic agents. Among the DNA binding modes, intercalation is the most important one, in which the molecules can intercalate between the base-pairs of double helix DNA, forming p–p overlapping interaction, and it is related to the antitumor activity of the molecule. 4 Nickel 5 and copper 6 complexes are regarded as most promising alternatives to platinum complexes as anticancer drugs. Nickel(II) complexes display interesting binding and cleavage reactivity with the nucleic acids. 7 Copper is known to play signicant role in bio- logical systems, as pharmacological agents and copper(II) complexes are found to exhibit prominent antitumor activity. 8 Phenolic Schiff base ligands have received increasing atten- tion because of their ease of formation, mixed hard–so donor character, versatile coordination behavior and their diversied applications. 9 Transition metal ions play a pivotal role in a vast number of diverse biological processes, and their metal complexes have been widely exploited, because of their unique spectral, electrochemical, magnetic and catalytic signatures but also due to the fact that by changing the ligand environment one can tune the DNA interaction of a metal complex. 10 A further reason for using metal containing compounds as structural scaffolds relates to the kinetic stabilities of their coordination spheres in the biological environment. 11 In past a Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai-600 014, Tamil Nadu, India. E-mail: akrahmanjkr@gmail. com; Fax: +91 44 2835 2883 b Department of Zoology, University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India † Electronic supplementary information (ESI) available: Tables S1–S5, Scheme S1 and Fig. S1–S10. CCDC 907779 and 952060. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra06941b Cite this: RSC Adv. , 2014, 4, 42855 Received 10th July 2014 Accepted 27th August 2014 DOI: 10.1039/c4ra06941b www.rsc.org/advances This journal is © The Royal Society of Chemistry 2014 RSC Adv., 2014, 4, 42855–42872 | 42855 RSC Advances PAPER