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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
N6-benzyladenosine derivatives as novel N-donor ligands of platinum(II) dichlorido complexes
Pavel Starha1, Igor Popa, Zdeněk Trávníček
1Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacký University, 17. Listopadu 12, CZ 77146 Olomouc, Czech Republic.
Abstract:
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.
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