A V-shaped ligand Bis(2-benzimidazolymethyl)amine (bba) and its nickel(II) picrate (pic) complex, with composition [Ni(bba)2](pic)2·3MeOH, have been synthesized and characterized on the basis of elemental analyses, molar conductivities, IR spectra, and UV/vis measurements. In the complex, the Ni(II) ion is six-coordinated with a N2O4 ligand set, resulting in a distorted octahedron coordination geometry. In addition, the DNA-binding properties of the Ni(II) complex have been investigated by electronic absorption, fluorescence, and viscosity measurements. The experimental results suggest that the nickel(II) complex binds to DNA by partial intercalation binding mode. 1. Introduction Binding studies of small molecules to DNA are very important in the development of DNA molecular probes and new therapeutic reagents [1]. Transition metal complexes have attracted considerable attention as catalytic systems for use in the oxidation of organic compounds [2], probes in electron-transfer reactions involving metalloproteins [3], and intercalators with DNA [4]. Numerous biological experiments have demonstrated that DNA is the primary intracellular target of anticancer drugs; interaction between small molecules and DNA can cause damage in cancer cells, blocking the division and resulting in cell death [5–7]. Since the benzimidazole unit is the key-building block for a variety of compounds which have crucial roles in the functions of biologically important molecules, there is a constant and growing interest over the past few years for the synthesis and biological studies of benzimidazole derivatives [8–10]. Since the characterization of urease as a nickel enzyme in 1975, the knowledge of the role of nickel in bioinorganic chemistry has been rapidly expanding [11]. The interaction of Ni(II) complexes with DNA appears to be mainly dependent on the structure of the ligand exhibiting intercalative behavior [12–14]. In this context, we synthesized and characterized a novel Ni(II) complex. Moreover, we describe the interaction of the novel Ni(II) complex with DNA using electronic absorption and fluorescence spectroscopy and viscosity measurements. 2. Experimental 2.1. Materials and Methods Calf thymus DNA (CT-DNA) and Ethidium bromide (EB) were purchased from Sigma Chemicals Co. (USA). All chemicals used were of analytical grade. All the experiments involving interaction of the ligand and the complexes with CT-DNA were carried out in doubly distilled water buffer containing 5?mM Tris and 50?mM NaCl and adjusted to pH 7.2 with hydrochloric acid. A solution of CT-DNA gave a
References
[1]
M. Mrksich and P. B. Dervan, “Antiparallel side-by-side heterodimer for sequence-specific recognition in the minor groove of DNA by a distamycin/1-methylimidazole-2-carboxamide-netropsin pair,” Journal of the American Chemical Society, vol. 115, no. 7, pp. 2572–2576, 1993.
[2]
C. Kokubo and T. Katsuki, “Highly enantioselective catalytic oxidation of alkyl aryl sulfides using Mn-salen catalyst,” Tetrahedron, vol. 52, no. 44, pp. 13895–13900, 1996.
[3]
S. Schoumacker, O. Hamelin, J. Pécaut, and M. Fontecave, “Catalytic asymmetric sulfoxidation by chiral manganese complexes: acetylacetonate anions as chirality switches,” Inorganic Chemistry, vol. 42, no. 24, pp. 8110–8116, 2003.
[4]
C. M. Dupureur and J. K. Barton, “Structural Studies of Λ- and Δ-[Ru(phen)2dppz]2+ Bound to d(GTCGAC)2: characterization of Enantioselective Intercalation,” Inorganic Chemistry, vol. 36, no. 1, pp. 33–43, 1997.
[5]
C. Hemmert, M. Pitié, M. Renz, H. Gornitzka, S. Soulet, and B. Meunier, “Preparation, characterization and crystal structures of manganese(II), iron(III) and copper(II) complexes of the bis[di-1,1-(2-pyridyl)ethyl] amine (BDPEA) ligand; evaluation of their DNA cleavage activities,” Journal of Biological Inorganic Chemistry, vol. 6, no. 1, pp. 14–22, 2001.
[6]
V. S. Li, D. Choi, Z. Wang, L. S. Jimenez, M. Tang, and H. Kohn, “Role of the C-10 substituent in mitomycin C-1-DNA bonding,” Journal of the American Chemical Society, vol. 118, no. 10, pp. 2326–2331, 1996.
[7]
G. Zuber, J. C. Quada, and S. M. Hecht, “Sequence selective cleavage of a DNA octanucleotide by chlorinated bithiazoles and bleomycins,” Journal of the American Chemical Society, vol. 120, no. 36, pp. 9368–9369, 1998.
[8]
A. Gellis, H. Kovacic, N. Boufatah, and P. Vanelle, “Synthesis and cytotoxicity evaluation of some benzimidazole-4,7-diones as bioreductive anticancer agents,” European Journal of Medicinal Chemistry, vol. 43, no. 9, pp. 1858–1864, 2008.
[9]
?. ?. Güven, T. Erdo?an, H. G?ker, and S. Yildiz, “Synthesis and antimicrobial activity of some novel phenyl and benzimidazole substituted benzyl ethers,” Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 8, pp. 2233–2236, 2007.
[10]
K. Kopańska, A. Najda, J. Zebrowska et al., “Synthesis and activity of 1H-benzimidazole and 1H-benzotriazole derivatives as inhibitors of Acanthamoeba castellanii,” Bioorganic and Medicinal Chemistry, vol. 12, no. 10, pp. 2617–2624, 2004.
[11]
K. C. Skyrianou, F. Perdih, I. Turel, D. P. Kessissoglou, and G. Psomas, “Nickel-quinolones interaction—part 2: interaction of nickel(II) with the antibacterial drug oxolinic acid,” Journal of Inorganic Biochemistry, vol. 104, no. 2, pp. 161–170, 2010.
[12]
K. C. Skyrianou, C. P. Raptopoulou, V. Psycharis, D. P. Kessissoglou, and G. Psomas, “Structure, cyclic voltammetry and DNA-binding properties of the bis(pyridine)bis(sparfloxacinato)nickel(II) complex,” Polyhedron, vol. 28, no. 15, pp. 3265–3271, 2009.
[13]
Y. Jin, M. A. Lewis, N. H. Gokhale, E. C. Long, and J. A. Cowan, “Influence of stereochemistry and redox potentials on the single- and double-strand DNA cleavage efficiency of Cu(II)-and Ni(II)·Lys-Gly-his-derived ATCUN metallopeptides,” Journal of the American Chemical Society, vol. 129, no. 26, pp. 8353–8361, 2007.
[14]
F. Bisceglie, M. Baldini, M. Belicchi-Ferrari et al., “Metal complexes of retinoid derivatives with antiproliferative activity: synthesis, characterization and DNA interaction studies,” European Journal of Medicinal Chemistry, vol. 42, no. 5, pp. 627–634, 2007.
[15]
J. B. Chaires, “Tris(phenanthroline)ruthenium(II) enantiomer interactions with DNA: mode and specificity of binding,” Biochemistry, vol. 32, no. 10, pp. 2573–2584, 1993.
[16]
J. Marmur, “A procedure for the isolation of deoxyribonucleic acid from microorganisms,” Methods in Enzymology, vol. 6, pp. 726–738, 1963.
[17]
A. Wolfe, G. H. Shimer, and T. Meehan, “Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA,” Biochemistry, vol. 26, no. 20, pp. 6392–6396, 1987.
[18]
M. Chauhan, K. Banerjee, and F. Arjmand, “DNA binding studies of novel copper(II) complexes containing L-tryptophan as chiral auxiliary: in vitro antitumor activity of Cu-Sn2 complex in human neuroblastoma cells,” Inorganic Chemistry, vol. 46, no. 8, pp. 3072–3082, 2007.
[19]
J. R. Lakowicz and G. Weber, “Quenching of fluorescence by oxygen. A probe for structural fluctuations in macromolecules,” Biochemistry, vol. 12, no. 21, pp. 4161–4170, 1973.
[20]
S. Satyanarayana, J. C. Dabrowiak, and J. B. Chaires, “Neither Δ- nor Λ-tris(phenanthroline)ruthenium(II) binds to DNA by classical intercalation,” Biochemistry, vol. 31, no. 39, pp. 9319–9324, 1992.
[21]
H. P. Berends and D. W. Stephan, “Copper(I) and copper(II) complexes of biologically relevant tridentate ligands,” Inorganica Chimica Acta, vol. 93, no. 4, pp. 173–178, 1984.
[22]
Bruker, Smart Saint and Sadabs, Bruker Axs, Inc., Madison, Wisc, USA, 2000.
[23]
G. M. Sheldrick, SHELXTL, Siemmens Analytical X-Ray Instruments, Inc., Madison, Wisc, USA, 1996.
[24]
W. J. Geary, “The use of conductivity measurements in organic solvents for the characterisation of coordination compounds,” Coordination Chemistry Reviews, vol. 7, no. 1, pp. 81–122, 1971.
[25]
C. Y. Su, B. S. Kang, C. X. Du, Q. C. Yang, and T. C. W. Mak, “Formation of mono-, bi-, tri-, and tetranuclear Ag(I) complexes of C3-symmetric tripodal benzimidaxole ligands,” Inorganic Chemistry, vol. 39, no. 21, pp. 4843–4849, 2000.
[26]
R. J. Sundberg and R. B. Martin, “Interactions of histidine and other imidazole derivatives with transition metal ions in chemical and biological systems,” Chemical Reviews, vol. 74, no. 4, pp. 471–517, 1974.
[27]
V. McKee, M. Zvagulis, and C. A. Reed, “Further insight into magnetostructural correlations in binuclear copper(II) species related to methemocyanin: X-ray crystal structure of a 1,2-μ-nitrito complex,” Inorganic Chemistry, vol. 24, no. 19, pp. 2914–2919, 1985.
[28]
T. J. Lane, I. Nakagawa, J. L. Walter, and A. J. Kandathil, “Infrared investigation of certain imidazole derivatives and their metal chelates,” Inorganic Chemistry, vol. 1, pp. 267–276, 1962.
[29]
H. Wu, R. Yun, K. Li, K. Wang, X. Huang, and T. Sun, “Synthesis, crystal structure and spectra properties of the nickel (II) complex with 1,3-bis(1-benzylbenzimidazol2-yl)-2-oxopropane,” Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, vol. 39, no. 9, pp. 614–617, 2009.
[30]
H. Li, X. Y. Le, D. W. Pang, H. Deng, Z. H. Xu, and Z. H. Lin, “DNA-binding and cleavage studies of novel copper(II) complex with L-phenylalaninate and 1,4,8,9-tetra-aza-triphenylene ligands,” Journal of Inorganic Biochemistry, vol. 99, no. 11, pp. 2240–2247, 2005.
[31]
V. G. Vaidyanathan and B. U. Nair, “Synthesis, characterization, and DNA binding studies of a chromium(III) complex containing a tridentate ligand,” European Journal of Inorganic Chemistry, no. 19, pp. 3633–3638, 2003.
[32]
V. G. Vaidyanathan and B. U. Nair, “Nucleobase oxidation of DNA by (terpyridyl)chromium(III) derivatives,” European Journal of Inorganic Chemistry, no. 9, pp. 1840–1846, 2004.
[33]
J. Liu, T. Zhang, T. Lu et al., “DNA-binding and cleavage studies of macrocyclic copper(II) complexes,” Journal of Inorganic Biochemistry, vol. 91, no. 1, pp. 269–276, 2002.
[34]
A. M. Pyle, J. P. Rehmann, R. Meshoyrer, C. V. Kumar, N. J. Turro, and J. K. Barton, “Mixed-ligand complexes of ruthenium(II): factors governing binding to DNA,” Journal of the American Chemical Society, vol. 111, no. 8, pp. 3051–3058, 1989.
[35]
B. C. Baguley and M. Le Bret, “Quenching of DNA-ethidium fluorescence by amsacrine and other antitumor agents: a possible electron-transfer effect,” Biochemistry, vol. 23, no. 5, pp. 937–943, 1984.