Spectroscopic study of the interaction of Ni II -5-triethyl ammonium methyl salicylidene ortho-phenylendiiminate with native DNA Giampaolo Barone a , Noemi Gambino a , Angela Ruggirello b , Arturo Silvestri a, * , Alessio Terenzi a , Vincenzo Turco Liveri b, * a Dipartimento di Chimica Inorganica e Analitica ‘‘S. Cannizzaro”, Università di Palermo, Viale delle Scienze, Parco d’Orleans II, Edificio 17, 90128 Palermo, Italy b Dipartimento di Chimica Fisica ‘‘F. Accascina”, Università di Palermo, Viale delle Scienze, Parco d’Orleans II, Edificio 17, 90128 Palermo, Italy article info Article history: Received 8 September 2008 Received in revised form 22 December 2008 Accepted 14 January 2009 Available online 22 January 2009 Keywords: DNA Intercalation Nickel Schiff bases Spectroscopy abstract The interaction of native calf thymus DNA with the cationic Ni(II) complex of 5-triethyl ammonium methyl salicylidene ortho-phenylendiimine (NiL 2+ ), in 1 mM Tris–HCl aqueous solutions at neutral pH, has been monitored as a function of the metal complex–DNA molar ratio by UV absorption spectropho- tometry, circular dichroism (CD) and fluorescence spectroscopy. The dramatic modification of the DNA CD spectrum, the appearance of a broad induced CD band in the range 350–400 nm, the strong increase of the DNA melting temperature (T m ) and the fluorescence quenching of ethidium bromide–DNA solu- tions, in the presence of increasing amounts of the NiL 2+ metal complex, support the existence of a tight intercalative interaction of NiL 2+ with DNA, analogous to that recently reported for both ZnL 2+ and CuL 2+ . The intrinsic binding constant (K b ) and the interaction stoichiometry (s), determined by UV spectropho- tometric titration, are equal to 4.3  10 6 M 1 and 1.0 base pair per metal complex, respectively. Interest- ingly, the value of K b is slightly higher and 10 times higher than that relative to the CuL 2+ –DNA and the ZnL 2+ –DNA systems, respectively. Speculations can be performed to rationalize the observed trend, on the basis of the electronic and geometrical structures of the three complexes of the same ligand. Analogously to what previously observed for CuL 2+ , the shape of the CD of the NiL 2+ –DNA system at NiL 2+ –DNA molar ratios higher than 0.5 is indicative of the formation of supramolecular aggregates in solutions, as a pos- sible consequence of the electrostatic interaction between the cationic complex and the negatively charged phosphate groups of DNA. Ó 2009 Elsevier Inc. All rights reserved. 1. Introduction The synthesis and biological (in particular antitumor) activity of first row transition metal complexes has been thoroughly investi- gated allowing to establish their great potentials as biomedical tools [1–3]. Among the various mechanisms through which they carry on their action, of utmost importance is their direct interaction with DNA. Several DNA binding studies have been reported [4–6]. In this respect, Ni(II) and Cu(II) complexes show DNA intercalative behav- ior and also DNA cleavage ability [7,8]. The ligand can be an aro- matic heterocyclic compound and often a Schiff base, the latter usually characterized by the presence of chelating NO and/or NS. The capability of DNA metallointercalators is determined by sev- eral factors such as the planarity of ligand, atom type of ligand do- nor and the coordination geometry [9]. Further necessary requisites that such complexes should obvi- ously possess are to be stable and inert in biological environment and water-soluble. The interaction among DNA and metal com- plexes containing multidentate aromatic ligands, with square planar N 4 or N 2 O 2 coordination, has been thoroughly considered [10–12]. Indeed, such compounds have some favorable features [11–15]: the ligand can be attached to the metal in a controlled manner; binding to DNA is usually accompanied by marked absor- bance changes in the UV–visible (UV-vis) frequency range and, sometimes, fluorescence emission too, due to excitation of charge transfer transitions. These properties, together with the analysis of the optical and thermal behavior of DNA in the presence of these metal complexes, provide a convenient handle for monitoring the binding process. Salen, the anion of the Schiff base [N,N 0 -ethylene-bis(salicylide- neimine)], H 2 Salen, and ligands obtained by its chemical modifica- tions fall in this class of compounds. Indeed, these ligands are characterized by a planar area with extended p system and coordi- nate metal atoms via a square planar N 2 O 2 system. Moreover, their metal complexes experience electronic transitions in the UV–vis range. 0162-0134/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jinorgbio.2009.01.006 * Corresponding authors. Fax: +39 091427584 (A. Silvestri), fax: +39 091590015 (V.T. Liveri). E-mail addresses: asilves@unipa.it (A. Silvestri), turco@unipa.it (V.Turco Liveri). Journal of Inorganic Biochemistry 103 (2009) 731–737 Contents lists available at ScienceDirect Journal of Inorganic Biochemistry journal homepage: www.elsevier.com/locate/jinorgbio