Substitution reactions of dinuclear platinum(II) complexes with some nitrogen nucleophiles Enisa Selimovic ´ • Tanja Soldatovic ´ • Jovana Bogojeski • Z ˇ ivadin D. Bugarc ˇic ´ Received: 15 October 2014 / Accepted: 6 November 2014 Ó Springer International Publishing Switzerland 2014 Abstract The substitution reactions of dinuclear Pt(II) com- plexes [{trans-Pt(NH 3 ) 2 Cl} 2 (l-pyrazine)] 2? (Pt1), [{trans- Pt(NH 3 ) 2 Cl} 2 (l-4,4 0 -bipyridyl)] 2? (Pt2), and [{trans-Pt(NH 3 ) 2 Cl} 2 (l-1,2-bis(4-pyridyl)ethane)] 2? (Pt3) and their aqua analogues with nitrogen-donor nucleophiles 1,2,4-triazole, L-histidine (His), and inosine-5 0 -monophosphate (5 0 -IMP) were studied under pseudo-first-order conditions as a func- tion of concentration and temperature using UV–Vis spec- trophotometry. The reactions of the chlorido complexes were followed in aqueous 25 mM Hepes buffer in the pre- sence of 20 mM NaCl at pH = 7.2, whilst the reactions of the aqua complexes were studied at pH 2.5 in 0.01 M Na- ClO 4 . Two consecutive reaction steps, which both depend on the nucleophile concentration, were observed. The order of reactivity of the investigated complexes is Pt1 [ Pt2 [ Pt3, and the order of reactivity of the nucleophiles is 1,2,4- triazole [ His [ 5 0 -IMP for both steps. The results indicate that the bridging ligand has an influence on the reactivity of the complexes toward nucleophiles. Introduction Anticancer drugs such as cisplatin, carboplatin, and oxa- liplatin are widely used for the treatment of different types of cancer [1–5]. However, these complexes also show harmful side effects such as nephrotoxicity, ototoxicity, neurotoxicity, cardiotoxicity [1–5]. Many studies have been focused on the search for new classes of platinum complexes with improved antitumor properties. The third- generation antitumor complexes such as sterically hindered and polynuclear Pt(II) complexes, sulfur-containing plati- num complexes, and orally active Pt(IV) complexes are now being tested in preclinical trials [6–9]. The development of Pt(II) complexes with more than one metal center, mainly dinuclear Pt(II) complexes, star- ted with the group of N. Farrell [10]. Dinuclear Pt(II) complexes form with DNA products that differ signifi- cantly in structure, sequence specificity, and formation kinetics from those of cisplatin [11]. The polynuclear Pt(II) complexes consist of either two or three platinum centers linked through a flexible bridge such as an aliphatic chain [12], or a rigid bridge that consists, for example, of azole moieties [13]. These polynuclear Pt(II) complexes are sufficiently flexible to provide 1,2-intrastrand cross-links with a minimal distortion of the DNA [11]. The biological activity of polynuclear Pt(II) complexes depends on their geometry and also on the nature of the linkers connecting the Pt(II) centers [14–16]. The five-membered azole rings with two or three nitrogen atoms have been found to be very important in bioinorganic chemistry. They can inhibit the binding of CO to the sodium dithionite-reduced ferrous cytochrome and can affect the activity of reconstituted P-450 by binding to the cytochrome in a 1:1 stoichiometry [17]. The imidazole group of L-histidine acts as a ligand in those hemoproteins Electronic supplementary material The online version of this article (doi:10.1007/s11243-014-9899-5) contains supplementary material, which is available to authorized users. E. Selimovic ´  T. Soldatovic ´ Department of Chemical-Technological Sciences, State University of Novi Pazar, Vuka Karadz ˇic ´a bb, 36300 Novi Pazar, Serbia J. Bogojeski  Z ˇ . D. Bugarc ˇic ´(&) Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovic ´a 12, P. O. Box 60, 34000 Kragujevac, Serbia e-mail: bugarcic@kg.ac.rs 123 Transition Met Chem DOI 10.1007/s11243-014-9899-5