Synthesis, characterization, structures and cytotoxic activity of palladium(II) and platinum(II) complexes containing bis(2-pyridylmethyl)amine and saccharinate Emel Guney a , Veysel T. Yilmaz a,⇑ , Ferda Ari b , Orhan Buyukgungor c , Engin Ulukaya d a Department of Chemistry, Faculty of Arts and Sciences, Uludag University, 16059 Bursa, Turkey b Department of Biology, Faculty of Arts and Sciences, Uludag University, 16059 Bursa, Turkey c Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayis University, 55139 Samsun, Turkey d Department of Medical Biochemistry, Faculty of Medicine, Uludag University, 16059 Bursa, Turkey article info Article history: Received 17 August 2010 Accepted 29 September 2010 Available online 7 October 2010 Keywords: Saccharinate Bis(2-pyridylmethyl)amine Palladium(II) Platinum(II) Water cluster Cytotoxic activity abstract New palladium(II) and platinum(II) complexes containing bis(2-pyridylmethyl)amine (bpma) and sac- charinate (sac), [Pd(bpma)(sac)](sac)Á2H 2 O(1), [Pt(bpma)(sac)](sac)Á2H 2 O(2), [Pd(bpma)Cl](sac)Á2H 2 O (3) and [Pt(bpma)(sac)]ClÁ1.5H 2 O(4), were synthesized and characterized by elemental analysis, IR, NMR and TG-DTA. A single-crystal X-ray analysis of 3 and 4 proved a distorted square–planar geometry around the metal ions with one tridentate bpma ligand and one Cl or sac monoanion. The [Pd(bpma)Cl] + ions in 3 form dimers by intermolecular N–HÁÁÁCl and PdÁÁÁPd interactions. The cations reside in the cen- ters of a hydrogen-bonded honeycomb network formed by the uncoordinated sac ions and the lattice water molecules, while the cations of 4 are connected by N–HÁÁÁCl and OW–HÁÁÁO hydrogen bonds into one-dimensional chains. Cyclic planar tetrameric and trimeric water clusters were observed in 3 and 4, respectively. Cytotoxicity of 1–4 was tested against A549, C6 and CHO cells. Although 2 and 4 have no cytotoxicity, the best results were achieved for 1 and 3. In particular, the cyctotoxic activity of 3 is com- parable to cisplatin. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction Cisplatin, chemically named as cis-diamminedichloroplati- num(II), is an extensively used cytotoxic anti-cancer drug [1]. Despite its remarkable success, several side effects such as the dose-dependent nephrotoxicity, neuorotoxicity and emetogensis are major medical problems associated with this drug [2]. Carbo- platin, cis-diammine(cyclobutane-1,1-dicarboxylate-O, O 0 )platinum(II), and oxaliplatin, (1R,2R)-cyclohexane-1,2-diamine](ethanedioato- O,O 0 )platinum(II), were approved as the second, and third plati- num-based drug generations, respectively [3,4]. Both platinum(II) complexes met requirements of improving antitumor activity and reducing disadvantages of cisplatin to some extent [5]. There- fore, there are demands for the design and synthesis of new metal complexes with high antitumor activity and less side effects in this field. On the other hand, palladium(II) complexes show similar chemical and structural properties with those of platinum(II) com- plexes and are, therefore, expected to have antitumor activity. Re- cent studies demonstrate that some palladium(II) complexes exhibit a noticeable in vitro cytotoxic activity, comparable to stan- dard platinum-based drugs, cisplatin, carboplatin and oxaliplatin [6]. The coordination chemistry of saccharin (sacH, also named 1,1- dioxo-1,2-benzothiazol-3-one or o-benzosulfimide) is interesting. SacH readily loses the amine hydrogen forming the saccharinate monoanion (sac) in solutions. Owing to the presence of the imino, carbonyl and sulfonyl donor sites, sac acts as a mono-, bi- or tri- dentate polyfunctional ligand and coordinates many transition me- tal ions, forming complexes from mononuclear species to coordination polymers [7]. Moreover, these donor sites together with the aromatic ring make sac as a good acceptor for non-cova- lent interactions such as hydrogen bonding and pÁÁÁp stackings. Our systematic studies have been directed to palladium(II) and platinum(II) complexes of sac, since palladium and platinum com- plexes of sac are rare and only a few complexes have been reported [8–12]. We have recently reported several palladium(II) and plati- num(II) complexes of sac with 2,2 0 :6 0 ,2 00 -terpyridine (terpy) [13], 2,2 0 -bipyridine (bpy) [14], 2,2 0 -dipyridylamine (dpya) [15], 2-ami- nomethyl (ampy) and -ethylpyridines (aepy) [16]. The cytotoxic activity of the palladium(II) and platinum(II) complexes with bpy and dpya was not tested due to their low solubility in common sol- vents. However, especially the palladium(II) complexes of terpy have demonstrated a distinct antitumor activity against a lung can- cer cell line (A549) compared to cisplatin [17]. To the best of our knowledge, the structure of palladium(II) and platinum(II)-bis(2- pyridylmethyl)amine (bpma) complexes with sac and their cycto- toxic activity have not been reported. Herein, we report the 0277-5387/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.poly.2010.09.037 ⇑ Corresponding author. E-mail address: vtyilmaz@uludag.edu.tr (V.T. Yilmaz). Polyhedron 30 (2011) 114–122 Contents lists available at ScienceDirect Polyhedron journal homepage: www.elsevier.com/locate/poly