DNA–DNA cross-linking mediated by bifunctional [SalenAl III ] + complex Arivazhagan Rajendran 1 , Chinnian J. Magesh, Paramasivan T. Perumal ⁎ Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, Tamil Nadu, India Received 18 September 2007; received in revised form 7 November 2007; accepted 19 November 2007 Available online 4 December 2007 Abstract The aluminum (III) complex [SalenAl III ]Cl (1), (Salen = (R,R)-N,N′-bis[5-methyl-3-(4-methylpiperazinyl)-salicylidene]-1,2-diphenylethane- diamine) has been synthesized and characterized by elemental analysis, FT-IR, 1 H and 13 C NMR measurements. The interaction of complex (1) with calf thymus (CT) DNA has been studied extensively by experimental techniques. Thermal denaturation study of DNA with (1) revealed the ΔT m of 5 ± 0.2 °C. Viscosity and steady-state fluorescence measurements showed that the complex cross-links DNA and the metal center is interacting with DNA during the cross-linking. Also, the phenyl ring in the complex may intercalate between the base pairs of the DNA during the cross-linking. Competitive binding study shows that the enhanced emission intensity of ethidium bromide (EB) in the presence of DNA was quenched by the addition of the metal complex indicating that it displaces EB from its binding site in DNA and the apparent binding constant has been estimated to be (2.8 ± 0.2) × 10 5 M - 1 . Further, time-resolved fluorescence experiments confirm the binding of (1) with DNA and its cross- linking nature. Aluminum ions shown to precipitate DNA completely above the pH 6.0, but no such precipitation was observed with complex (1). The DNA–DNA cross-linking mediated by (1) is further confirmed by gel electrophoresis. © 2007 Elsevier B.V. All rights reserved. Keywords: Metal–Salen complex; Al (III) complex; DNA-binding; DNA–DNA cross-linking 1. Introduction Studies on the interaction of small molecules with nucleic acid have gained prominence, because of their relevance in the development of new reagents for biotechnology and medicine [1–3]. These studies are also important for the development of probes for nucleic acid structure and conformational determina- tion [4]. Metal complexes have been widely exploited for these purposes because of their unique spectral and electrochemical signatures and also by changing the ligand environment one can tune the DNA binding affinity and cleaving ability of a metal complex. For instance, CrCl 3 has been found to induce DNA– DNA cross-linking [5], whereas chromium (III) complexes of the Schiff bases (salen and salprn) do not bring about any DNA–DNA cross-linking [6]. On the contrary, these complexes exhibit conformational changes in super coiled DNA in the presence of hydrogen peroxide and this is consistent with oxygen radical mediated cleavage. Several metal complexes have been used as probes for DNA structure in solution, as agents for mediation of strand scission of duplex DNA [7,8] and as chemotherapeutic agents [9,10]. Some metal complexes bind covalently to DNA and function as anti-tumor agents. Even though interaction and binding modes of several metal ions with DNA have been the subject of many investigations, interaction of Al (III) with DNA has not attracted much attention. Aluminum is a known neurotoxic agent and interferes with a large number of neurochemical reactions in vivo [11–13]. Studies in experimental animals as well as circumstantial evi- dence provided clues that Al might be one of the suspected and also highly debatable factors causing neuronal cell death in neurodegenerative brain [14]. The neurotoxic effects of Al could be due to its binding to DNA. The pH and concentration dependent interaction of Al with DNA has been reported previously [15,16]. Bharathi et al. [17] have described the interaction of Al–amino acid complexes with DNA at pH 7.0 which is likely of physiological relevance. Available online at www.sciencedirect.com Biochimica et Biophysica Acta 1780 (2008) 282 – 288 www.elsevier.com/locate/bbagen ⁎ Corresponding author. Tel.: +91 44 24913289; fax: +91 44 24911589. E-mail addresses: raj_12980@yahoo.co.in (A. Rajendran), ptperumal@gmail.com (P.T. Perumal). 1 Present address: Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan. 0304-4165/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.bbagen.2007.11.012