The platinum(II) complexes trans-[PtCl₂(Ln)₂]∙xSolv 1-13 (Solv = H₂O or CH3OH), involving N6-benzyladenosine-based N-donor ligands, were synthesized; L(n) stands for N6-(2-methoxybenzyl)adenosine (L₁, involved in complex 1), N6-(4-methoxy-benzyl)adenosine (L₂, 2), N6-(2-chlorobenzyl)adenosine (L₃, 3), N6-(4-chlorobenzyl)-adenosine (L₄, 4), N6-(2-hydroxybenzyl)adenosine (L₅, 5), N6-(3-hydroxybenzyl)-adenosine (L₆, 6), N6-(2-hydroxy-3-methoxybenzyl)adenosine (L₇, 7), N6-(4-fluoro-benzyl)adenosine (L₈, 8), N6-(4-methylbenzyl)adenosine (L₉, 9), 2-chloro-N6-(3-hydroxy-benzyl)adenosine (L₁₀, 10), 2-chloro-N6-(4-hydroxybenzyl)adenosine (L₁₁, 11), 2-chloro-N6-(2-hydroxy-3-methoxybenzyl)adenosine (L₁₂, 12) and 2-chloro-N6-(2-hydroxy-5-methylbenzyl)adenosine (L₁₃, 13). The compounds were characterized by elemental analysis, mass spectrometry, IR and multinuclear (¹H-, ¹³C-, ¹⁹⁵Pt- and ¹⁵N-) and two-dimensional NMR spectroscopy, which proved the N7-coordination mode of the appropriate N6-benzyladenosine derivative and trans-geometry of the title complexes. The complexes 1-13 were found to be non-toxic in vitro against two selected human cancer cell lines (HOS and MCF7; with IC₅₀ > 50.0 µM). However, they were found (by ESI-MS study) to be able to interact with the physiological levels of the sulfur-containing biogenic biomolecule L-methionine by a relatively simple 1:1 exchange mechanism (one L(n) molecule was replaced by one L-methionine molecule), thus forming a mixed-nitrogen/sulfur-ligand dichlorido-platinum(II) coordination species.

Regional Centre of Advanced Technologies and Materials Department of Inorganic Chemistry Faculty of Science Palacký University 17 Listopadu 12 CZ 77146 Olomouc Czech Republic

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Evaluate Ltd. EvaluatePharma® Coverage of Marketed and Pipeline Products (Platinum Compounds) [(accessed on 24 April 2013)]. Available online: http://www.evaluategroup.com/Universal/View.aspx?type =Entity&entityType=Product&lType=modData&id=438&componentID=1003/

Kauffmann G.B., Pentimalli R., Doldi S., Hall M.D. Michele Peyrone (1813–1883), Discoverer of Cisplatin. Platinum Metals Rev. 2010;54:250–256. doi: 10.1595/147106710X534326. DOI

Rosenberg B., VanCamp L., Trosko J.E., Mansour V.H. Platinum compounds: A new class of potent antitumour agents. Nature. 1969;222:385–386. doi: 10.1038/222385a0. PubMed DOI

Perez J.M., Fuertes M.A., Alonso C., Navarro-Ranninger C. Current status of the development of trans-platinum antitumor drugs. Crit. Rev. Oncol./Hematol. 2000;35:109–120. doi: 10.1016/S1040-8428(00)00053-6. PubMed DOI

Kalinowska-Lis U., Ochocki J., Matlawska-Wasowska K. Trans geometry in platinum antitumor complexes. Coord. Chem. Rev. 2008;252:1328–1345. doi: 10.1016/j.ccr.2007.07.015. DOI

Farrell N., Ha T.T.B., Souchard J.P., Wimmer F.L., Cros S., Johnson N.P. Cytostatic trans-platinum(II) complexes. J. Med. Chem. 1989;32:2240–2241. doi: 10.1021/jm00130a002. PubMed DOI

Montero E.I., Díaz S., González-Vadillo A.M., Pérez J.M., Alonso C., Navarro-Ranninger C. Preparation and characterization of novel trans-[PtCl 2(amine)(isopropylamine)] compounds. Cytotoxic activity and apoptosis induction in ras-transformed cells. J. Med. Chem. 1999;42:4264–4268. doi: 10.1021/jm991015e. PubMed DOI

Bocarelli A., Coluccia M., Intini F.P., Natile G., Locker D., Leng M. Cytotoxicity and DNA binding mode of new platinum-iminoether derivatives with different configuration of the iminoether ligands. Anti-Cancer Drug Des. 1999;14:253–264. PubMed

Coluccia M., Nassi A., Bocarelli A., Giordano D., Cardellicchio N., Locker D., Leng M., Sivo M., Intini F.P., Natile G. In vitro and in vivo antitumor activity of and cellular pharmacological properties of new platinum-iminoether complexes with different configuration of the iminoether ligands. J. Inorg. Biochem. 1999;77:31–35. doi: 10.1016/S0162-0134(99)00139-7. PubMed DOI

Perego P., Caserini C., Gatti L., Carenni N., Romanelli S., Supino R., Colangelo D., Viano Y., Leone R., Spinelli S., et al. A novel trinuclear platinum complex overcomes cisplatin resistance in an osteosarcoma cell system. Mol. Pharm. 1999;55:528–534. PubMed

Skoog F., Hamzi H.G., Szweykowska A.M., Leonard N.J., Carraway K.L., Fujii T., Helgeson J.P., Loeppky R.N. Cytokinins: Structure/activity relationships. Phytochemistry. 1967;6:1169–1192.

Doležal K., Popa I., Zatloukal M., Lenobel R., Hradecká D., Vojtěšek B., Uldrijan S., Mlejnek P., Werbrouck S., Strnad M. Substitution derivatives of N6-benzyladenosine, methods of their preparation, their use for preparation of drugs, cosmetic preparations and growth regulators, pharmaceutical preparations, cosmetic preparations and growth regulators containing these compounds. 8,119,614 B2. U.S. Patent. 2012 Feb 21;

Doležel P., Koudelková P., Mlejnek P. Halogenation of N6-benzyladenosine decreases its cytotoxicity in human leukemia cells. Toxicol. In Vitro. 2010;24:2079–2083. doi: 10.1016/j.tiv.2010.07.010. PubMed DOI

Waysbort D., Tarien E., Eichhorn G.L. Nature of the specific interaction of rhodium acetate dimer with adenosine. Inorg. Chem. 1993;32:4774–4779. doi: 10.1021/ic00074a020. DOI

Trávníček Z., Mikulík J., Čajan M., Zbořil R., Popa I. Novel iron complexes bearing N6-substituted adenosine derivatives: Synthesis, magnetic, 57Fe Mossbauer, DFT, and in vitro cytotoxicity studies. Bioorg. Med. Chem. 2008;16:8719–8728. doi: 10.1016/j.bmc.2008.07.082. PubMed DOI

Szüčová L., Trávníček Z., Popa I., Marek J. Preparation and cis-to-trans transformation study of square-planar [Pt(Ln)2Cl2] complexes bearing cytokinins derived from 6-benzylaminopurine (Ln) by view of NMR spectroscopy and X-ray crystallography. Polyhedron. 2008;27:2710–2720. doi: 10.1016/j.poly.2008.05.021. DOI

Štarha P., Trávníček Z., Popa A., Popa I., Muchová T., Brabec V. How to modify 7-azaindole to form cytotoxic Pt(II) complexes: Highly in vitro anticancer effective cisplatin derivatives involving halogeno-substituted 7-azaindole. J. Inorg. Biochem. 2012;115:57–63. doi: 10.1016/j.jinorgbio.2012.05.006. PubMed DOI

Geary W.J. The use of conductivity measurements in organic solvents for the characterization of coordination compounds. Coord. Chem. Rev. 1971;7:81–122. doi: 10.1016/S0010-8545(00)80009-0. DOI

Pouchert C.J. The Aldrich Library of Infrared Spectra. Aldrich Chemical Company Press; Milwaukee, WI, USA: 1981.

Čajan M., Trávníček Z. Structural (X-ray), spectral (FT-IR and Raman) and quantum chemical investigations of a series of 6-benzylaminopurine derivatives. J. Mol. Struct. 2011;994:350–359. doi: 10.1016/j.molstruc.2011.03.049. DOI

Nakamoto K. Infrared and Raman Spectra of Inorganic and Coordination Compounds. Part B: Applications in Coordination, Organometallic and Bioinorganic Chemistry. John Wiley & Sons Ltd.; New York, NY, USA: 1991.

Terzis A., Hadjiliadis N., Rivest R., Theophanides T. X-ray crystal structure of a platinum-9-methyladenine complex. Inorg. Chim. Acta. 1975;12:L5–L6. doi: 10.1016/S0020-1693(00)89808-4. DOI

Wexselblatt E., Gibson D. What do we know about the reduction of Pt(IV) pro-drugs? J. Inorg. Biochem. 2012;117:220–229. doi: 10.1016/j.jinorgbio.2012.06.013. PubMed DOI

Sanchez-Canoa C., Hannon M.J. Novel and emerging approaches for the delivery of metallo-drugs. Dalton Trans. 2009:10702–10711. doi: 10.1039/b912708a. PubMed DOI

Chung J.S., Haque R., Guha Mazumder D.N., Moore L.E., Ghosh N., Samanta S., Mitra S., Hira-Smith M.M., von Ehrenstein O., Basu A., et al. Blood concentrations of methionine, selenium, beta-carotene, and other micronutrients in a case-control study of arsenic-induced skin lesions in West Bengal, India. Environ. Res. 2006;101:230–237. doi: 10.1016/j.envres.2005.10.006. PubMed DOI

Videhult P., Laurell G., Wallin I., Ehrsson H. Kinetics of cisplatin and its monohydrated complex with sulfur-containing compounds designed for local otoprotective administration. Exp. Biol. Med. 2006;231:1638–1645. PubMed

Farrell N., Kelland L.R., Roberts J.D., Van Beusichem M. Activation of the trans geometry in platinum antitumor complexes: a survey of the cytotoxicity of trans complexes containing planar ligands in murine L1210 and humar tumor panels and studies on their mechanism of action. Cancer Res. 1992;52:5065–5072. PubMed

Kuhnle J.A., Fuller G., Corse J., Mackey B.E. Anti-senescent activity of natural cytokinins. Physiol. Plantarum. 1977;41:14–21. doi: 10.1111/j.1399-3054.1977.tb01514.x. DOI

Novikov A.V., Bublyaev R.A., Krasnov N.V., Kozmin Y.P., Mirgorodskaya O.A. ESI-MS studies of silver ion competitive interaction with cysteine-containing peptides and sulfur-containing amino acids. Protein Pept. Lett. 2010;17:1392–1397. doi: 10.2174/0929866511009011392. PubMed DOI

Canon F., Paté F., Meudec E., Marlin T., Cheynier V., Giuliani A., Sarni-Manchado P. Characterization, stoichiometry, and stability of salivary protein-tannin complexes by ESI-MS and ESI-MS/MS. Anal. Bioanal. Chem. 2009;395:2535–2545. PubMed

Sandercock A., Robinson C. Electrospray Ionization Mass Spectrometry and the Study of Protein Complexes. In: Schuck P., editor. Protein Interactions. Volume 1. Springer; New York, NY, USA: 2007. pp. 447–468.

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