Speciation Studies of Diorganotin(IV) Complexes with 3,3-Bis(1-methylimidazol-2-yl)propionate—Displacement Reaction by DNA Constituents

Hindawi Publishing Corporation The Scientific World Journal Volume 2013, Article ID 106357, 7 pages http://dx.doi.org/10.1155/2013/106357 Research Article Speciation Studies of Diorganotin(IV) Complexes with 3,3-Bis(1-methylimidazol-2-yl)propionate—Displacement Reaction by DNA Constituents Mohamed M. Shoukry1,2 and Safaa S. Hassan2 1 2 Department of Chemistry, Faculty of Science, Islamic University, Madina 170, Saudi Arabia Depatment of Chemistry, Faculty of Science, Cairo University, Cairo 12613, Egypt Correspondence should be addressed to Mohamed M. Shoukry; Received 15 August 2013; Accepted 17 September 2013 Academic Editors: M. Pellei and A. Souldozi Copyright © 2013 M. M. Shoukry and S. S. Hassan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The interaction of 3,3-bis(1-methylimidazol-2-yl)propionate (BIMP) with dimethyltin(IV) dichloride (DMT), dibutyltin(IV) dichloride (DBT), and diphenyltin(IV) dichloride (DPT) is investigated at 25∘ C and 0.1 M ionic strength in water for dimethyltin(IV), and in a 50% dioxane-water mixture for dibutyltin(IV) and diphenyltin(IV). The stepwise formation constants of the 1 : 1 and 1 : 2 complexes formed in solution are calculated from potentiometric measurements using the nonlinear least-square program MINIQUAD-75. The concentration distribution of the various complex species is evaluated as a function of pH. Displacement reactions of the coordinated 3,3-bis(1-methylimidazol-2-yl)propionate by inosine and inosine-5󸀠 -monophosphate are investigated from calculations based upon equilibrium properties. 1. Introduction There has been tremendous research in recent years concerning the design of nonplatinum chemotherapeutics with the aim to optimize the features of classical platinum drugs constituting the basic cisplatin framework without some of their drawbacks, namely, toxic side effects, inherent intrinsic resistance, and high cost [1]. Among other noteworthy possibilities, some organotin compounds have emerged as a promising class of cancer chemotherapeutics. The antitumour properties of tin complexes have been established since 1929 [2] and Gielen [3] has published a series of research papers on this subject during the past two decades. The diorganotin (IV) antitumour complexes showed high in vitro activity against P388 leukaemia in mice as well as in some human tumour cell lines [4–10]. Numerous diorganotin (IV) derivatives have been found to exhibit high in vivo cytotoxicity against P388 lymphocytic leukaemia and to exhibit less or no activity against other murine systems [11]. However, the new in vitro human tumour cell screening tests have once again demonstrated the potential of organotin complexes, some of which have exhibited high activity [12], and thus interest in them has been revitalized. Organotin (IV) compounds exhibiting potent anticancer activity may act via different mechanisms at the molecular level. The binding property of organotin compounds towards DNA, the ultimate drug target molecule, depends essentially on the coordination number/stereochemistry and the nature of groups directly attached to the tin scaffold [13]. Recently, there have been reports of the interaction of Sn compounds with DNA constituents [14–16]. The antitumour activity of the coordination compounds R2 SnX2 L2 is controlled by the nature of R, leaving groups (X) and the ligand (L). The coordinated ligand (L) favours in some way the transport of the drugs into cells, while the antitumour activity would be exerted by the diorganotin(IV) moiety dissociated from the complex [17]. The latter would interact with nucleic acids, in a similar way as in the case of the widely used anticancer drug cisplatin. Therefore, there is a relationship between the stability of the organotin(IV) compounds and their antitumor activity. In conjunction with our previous studies on organotin (IV) complexes [18–22], the present paper aims to study 2 The Scientific World Journal N H3 C N COOH N N CH3 3,3-bis(1-methylimidazol-2-yl)propionic acid O O HN 1 6 N 7 3 N 9 N N 7 HN 1 OH O 3 N 9 N O− O O O P − O OH OH Inosine OH OH Inosine-5󳰀 -monophosphate Scheme 1: Chemical structure of investigated ligands. dimethyl-, dibutyl-, and diphenyltin(IV) complexes with 3,3bis(1-methylimidazol-2-yl)propionate (BIMP). The displacement reaction of coordinated (BIMP) by inosine and inosine5󸀠 -monophosphate, taken as representative examples of DNA constituents, is investigated. The equilibrium constant for the displacement reaction is a parameter that may be significant to the antitumor activity of organotin(IV) compounds. 2. Experimental Dimethyltin(IV) dichloride(DMT), dibutyltin(IV) dichloride (DBT), and diphenyltin(IV) dichloride (DPT) were obtained from the Merck Chem. Co. 3,3-bis(1-methylimidazol-2-yl)propionate (BIMP) was prepared as described previously [23]. Inosine and inosine-5’-monophosphate were obtained from Aldrich Chem. Co. The chemical structure of the investigated ligands were given in Scheme 1. Carbonatefree NaOH (titrant) was prepared and standardized against potassium hydrogen phthalate solution. DMT solution was prepared in water, but DBT and DPT solutions were prepared in dioxane. BIMP solution was prepared in the protonated form by dissolving in HNO3 solution. Potentiometric measurements were made using a Metrohm 686 titroprocessor equipped with a 665 Dosimat (Switzerland). The titroprocessor and electrode were calibrated with standard buffer solutions and prepared according to NBS specifications [24]. The titrations were carried out in a purified N2 atmosphere using a titration vessel described previously [25]. The temperature was maintained constant by a Colora ultrathermostat. The protonation constants of 3,3bis(1-methylimidazol-2-yl)propionic acid in the protonated form were determined by titrating 40 mL of a 2.5 × 10−3 M solution. The hydrolysis constants of the DMT, DBT, and DPT compounds were determined by titrating 40 mL solution of concentration 2.5 × 10−3 M of each compound. The formation constants of organotin(IV) complexes were determined by titrating 40 mL of solution containing 3,3-bis(1methylimidazol-2-yl)propionate (2.5 × 10−3 M) and a given organotin(IV) compound with a concentration of 1.25 × 10−3 M. The titration was performed at 25∘ C and in water for DMT but in 50% dioxane-water solution for DBT and DPT. The 𝑝𝐾w in dioxane-water solution was determined as described previously [22, 26]. For this purpose, various amounts of standard NaOH solution were added to a solution containing 0.1 M NaNO3 . The [OH− ] was calculated from the amount of base added. The [H+ ] was calculated from the pH value. The product of [OH− ] and [H+ ] was taken. The mean value obtained in this way for the log concentration product is 𝑝𝐾w = 15.46 for 50% dioxane-wa (...truncated)