In vitro binding studies of organotin(IV) complexes of 1,2-bis(1H-benzimidazol- 2-yl)ethane-1,2-diol with CT-DNA and nucleotides (5 0 -GMP and 5 0 -TMP): Effect of the ancillary ligand on the binding propensity Farukh Arjmand * , Fatima Sayeed, Shazia Parveen Department of Chemistry, Aligarh Muslim University, Aligarh, UP 202002, India article info Article history: Received 11 May 2011 Received in revised form 9 August 2011 Accepted 14 August 2011 Keywords: Organotin(IV) complexes DNA binding 5 0 -GMP & 5 0 -TMP Circular dichroism abstract The chiral benzimidazole ligand, 1,2-Bis(1H-benzimidazol-2-yl)ethane-1,2-diol, L, exhibiting coordina- tion mode with an oxygen atom of alcohol group directed towards the metal ion and another eOH group with different molecular axis directed away from the metal center was utilized as a building block for organotin complexes [C 18 H 19 N 4 O 2 SnCl], [C 28 H 23 N 4 O 2 SnCl] and [C 52 H 42 N 4 O 2 Sn 2 ](1e3). Complexes 1 and 3 exhibit a pentacoordinate geometry while the complex 2 reveals hexacoordinated environment around the Sn(IV) metal ions as evidenced by 119 Sn NMR studies. The DNA binding ability of benzimidazole ligand and their organotin(IV) complexes 1e3 were examined by employing different biophysical methods. The absorption titration of the complexes with CT-DNA reveal significant hyperchromic effect together with strong bathochromic shift of 4e5 nm which infer substantial binding of the complexes with CT-DNA. The intrinsic binding constant K b values of the complexes 1e3 were found to be 2.16  0.04  10 4 , 3.47  0.04  10 4 and 4.60  0.04  10 3 M 1 , respectively, suggesting pronounced binding of complex 2 with DNA double helix. The mechanism of binding of the complexes was further ascertained by the interaction studies of these complexes with nucleotides (5 0 -GMP and 5 0 -TMP) using absorption spectroscopy suggesting a clear preference for 5 0 -GMP binding which was further authenti- cated by NMR ( 1 H and 31 P NMR) studies. Ó 2011 Elsevier B.V. All rights reserved. 1. Introduction Spectacular success of cisplatin, cis-diamminedichloroplati- num(II) [1], an archetypical inorganic drug for treating solid cancers led to the discovery of many other second generation drugs such as oxaliplatin, carboplatin, picoplatin, etc., however owing to the limitations of platinum drugs, such as severe side effects, intrinsic and extrinsic resistance; and also since cancers are derived from numerous tissues with new multiple etiologies, therefore, these compounds cannot be potent (cytotoxic) against different the phenotypes of tumors [2], thus a resurging need for the developing new non-platinum metal compounds was realized. In the forefront on therapeutic regime are organotin compounds which have since 1972 demonstrated their cytotoxic activity (one compound tri- phenyltin acetate was shown to retard tumor growth in mice while its chloride derivative did not show any potency) [3]. Since then, a large number of organotin derivatives have been prepared and tested in vitro and in vivo, against murine leukemia cell lines [4]. Recent reports in literature reveal synthesis of many organotin metal complexes and their DNA binding studies [5e8]. Most of the compounds tested earlier exhibited interesting activity in specific cancer models, but often lacked activity against broad spectrum of experimental tumors. Nevertheless, there is possibility for variation of organic moieties and donor ligands linked to metal which can result in several organotin with high antitumor activity [9]. The ligand framework plays a significant role in metal-based pharma- ceuticals via alteration in the biological properties by modifying reactivity or substitution inertness [10]. The effects of varying substituents of organotin(IV) metal ions both aliphatic and aromatic were studied as it is well known that the biological effects of organotins depends on both the nature and number of organic groups bound to Sn(IV) cation. Besides this, introduction of an element of chirality is an attractive prospect as it could enhance the pharmacological uptake of the drug entity by adopting specific conformation and stereo- selective binding with molecular target DNA [11]. We have been interested in a chiral tridentate ligand 1,2-Bis(1H-benzimidazol-2- yl)ethane-1,2-diol, as it is a versatile tridentate facially coordinating * Corresponding author. Tel.: þ91 5712703893. E-mail address: farukh_arjmand@yahoo.co.in (F. Arjmand). Contents lists available at SciVerse ScienceDirect Journal of Organometallic Chemistry journal homepage: www.elsevier.com/locate/jorganchem 0022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jorganchem.2011.08.007 Journal of Organometallic Chemistry 696 (2011) 3836e3845