Synthesis, Characterization, and Biological Studies of Organotin(IV) Derivatives with o- or p-hydroxybenzoic Acids

Hindawi Publishing Corporation Bioinorganic Chemistry and Applications Volume 2009, Article ID 542979, 12 pages doi:10.1155/2009/542979 Research Article Synthesis, Characterization, and Biological Studies of Organotin(IV) Derivatives with o- or p-hydroxybenzoic Acids Mohamed A. Abdellah,1, 2 Sotiris K. Hadjikakou,1 Nick Hadjiliadis,1 Maciej Kubicki,3 Thomas Bakas,4 Nikolaos Kourkoumelis,4, 5 Yannis V. Simos,6 Spyros Karkabounas,6 Mirela M. Barsan,7 and Ian S. Butler7 1 Section of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece 2 Department of Chemistry, Qena Faculty of Science, South Valley University, Qena 83523, Egypt 3 Faculty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznan, Poland 4 Physics of Material Laboratory, Department of Physics, University of Ioannina, 45110 Ioannina, Greece 5 Medical Physics Laboratory, Medical School, University of Ioannina, 45110 Ioannina, Greece 6 Department of Experimental Physiology, Medical School, University of Ioannina, 45110 Ioannina, Greece 7 Department of Chemistry, McGill University, 801 Sherbrooke, Montreal QC, Canada H2A 2K6 Correspondence should be addressed to Sotiris K. Hadjikakou, Received 6 November 2008; Accepted 14 January 2009 Recommended by Lorenzo Pellerito Organotin(IV) complexes with o- or p-hydroxybenzoic acids (o-H2 BZA or p-H2 BZA) of formulae [R2 Sn(HL)2 ] (where H2 L = o-H2 BZA and R = Me- (1), n-Bu- (2)); [R3 Sn(HL)] (where H2 L = o-H2 BZA and R = n-Bu- (3), Ph- (4) or H2 L = p-H2 BZA and R = n-Bu- (5), Ph- (6)) were synthesized by reacting a methanolic solution of di- and triorganotin(IV) compounds with an aqueous solution of the ligand (o-H2 BZA or p-H2 BZA) containing equimolar amounts of potassium hydroxide. The complexes were characterized by elemental analysis, FT-IR, Far-IR, TGA-DTA, FT-Raman, Mössbauer spectroscopy, 1 H, 119 Sn-NMR, UV/Vis spectroscopy, and Mass spectroscopy. The X-ray crystal structures of complexes 1 and 2 have also been determined. Finally, the influence of these complexes 1–6 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically studied and the results showed that triorganotin(IV) complex 6 has the lowest IC50 value. Also complexes 1–6 were studied for their in vitro cytotoxicity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, and the results showed that the complexes have high activity against these cell lines with triphenyltin((IV) complex 4 to be the most active one. Copyright © 2009 Mohamed A. Abdellah et al. 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. 1. Introduction Organotin compounds have many important applications and uses [1, 2]. Commercially, organotin compounds are used as industrial and agricultural biocides because they have high antifungal properties [3, 4]. The in vitro fungicidal or antibacterial properties of organotins have been found to exhibit the general order of activity: RSnX3 < R2 SnX2 < R4 Sn  R3 SnX, with the anionic X group to exert little influence on activity [5, 6]. The combination of two biologically active entities, however, in the same molecule could enhance their activity [7]. For example, triphenyltin(IV) derivatives of phthalic acid and salicaldehyde have significant activity toward a range of fungi [8, 9]. Recently, interests in organotin(IV) carboxylates are increasing due to their possible medical uses as antitumor agents [10]. For example, the fluoro-substituted carboxylate ligands with di- and triorganotins produced several antitumor active compounds [11]. Hubert et al. concluded that antitumor active tin compounds possess available coordination positions around tin atom and also have relatively stable ligand-tin bonds with low hydrolytic decomposition [12]. Thioamides-organotin complexes, on the other hand, have shown high antitumor activity, which is rather related to the ligand type and not to the geometry of the compounds [13–17]. Given that the antitumor action of Sn(IV) compounds may not be due 2 Bioinorganic Chemistry and Applications a b a b OH a OH HO O O b b OH a (II) (I) Scheme 1 to their direct interaction with DNA constituents [18–22], their reaction with enzymes like lipoxygenase is always of interest in the attempt to elucidate their mechanism of action [13–17]. This antitumor activity of the organotin complexes follows the same order of lipoxygenase inhibition, an enzyme taking part in the inflammation mechanism and tumor genesis [13–17]. With the aim to prepare new organotin(IV-)-based antitumor compounds of o- or p-hydroxybenzoic acid (Schemes 1 (I) and (II), resp.), the synthesis of six organotin complexes of formulae [R2 Sn(HL)2 ] (where H2 L = o-H2 BZA and R = Me- (1), n-Bu- (2)) and [R3 Sn(HL)], (where H2 L = oH2 BZA and R = n-Bu- (3), Ph- (4) or H2 L = p-H2 BZA, and R = n-Bu- (5), Ph- (6)) and their characterization by spectroscopic techniques (IR, Raman,1 H-NMR, mass Spectra, 119m Sn Mössbauer, UV/Vis), elemental analysis and X-ray diffraction have been carried out. The inhibition caused by these complexes toward the oxidation of linoleic acid to hyperoxolinoleic acid by the enzyme lipoxygenase (LOX) follow the order 6 > 4 > 5 > 2 > 1 > 3 and compared with their in vitro antitumor activity against sarcoma cells, where the order is 4 > 6 > 5  3 = 2  1. Therefore, triorganotin compounds inhibit stronger lipoxygenase and show higher activity against sarcoma cells than diorganotins. 2. Results and Discussion 2.1. General Aspects. Organotin(IV) complexes 1–6 have been synthesized by reacting a methanolic solution of organotin chloride with an aqueous solution of the appropriate amounts of 2- or 4-hydroxybenzoic acid containing an equimolar amount of potassium hydroxide as shown in (1) and (2): MeOH/H O 2 → R2 SnCl2 + 2H2 L + 2KOH −−−−−−− R2 Sn(HL2 ) + 2KCl + 2H2 O H2 L = o-H2 BZA and R = Me- (1), n-Bu- (2) (1) MeOH/H O 2 R3 SnCl + H2 L + KOH −−−−−−− → R3 Sn(HL) + KCl + H2 O H2 L = o-H2 BZA and R = n-Bu- (3), Ph- (4) or H2 L = p-H2 BZA and R = n-Bu- (5), Ph- (6). (2) Complexes 1-2 were prepared with an alternative method of the one used previously for the synthesis of these complexes [23, 24]. Complexes 1–6 are air-stable powders soluble in methanol, ethanol, and DMSO solvents. Crystals suitable for X-ray analysis were obtained by slow evaporation of methanol/acetonitril solutions for compounds 1 and 2. 2.2. Thermal Analysis. The TGA/DTA data curves for complexes 1-2 show that they decompose generally in one stage. Thus, thermal analysis in flowing nitrogen shows that complex 1 decomposes between 125 and 315◦ C with 72% mass loss which corresponds to the methyl groups of the metal and the ligand molecules (the calculated mass loss is 72%), c (...truncated)