N6-Benzyladenosine Derivatives as Novel N-Donor Ligands of Platinum(II) Dichlorido Complexes

Abstract

The platinum(II) complexes trans-[PtCl ₂(L _n) ₂]∙ xSolv 1– 13 (Solv = H ₂O or CH ₃OH), involving N6-benzyladenosine-based N-donor ligands, were synthesized; L _n stands for N6-(2-methoxybenzyl)adenosine ( L ₁ , involved in complex 1), N6-(4-methoxy-benzyl)adenosine ( L ₂ , 2), N6-(2-chlorobenzyl)adenosine ( L ₃ , 3), N6-(4-chlorobenzyl)-adenosine ( L ₄ , 4), N6-(2-hydroxybenzyl)adenosine ( L ₅ , 5), N6-(3-hydroxybenzyl)-adenosine ( L ₆ , 6), N6-(2-hydroxy-3-methoxybenzyl)adenosine ( L ₇ , 7), N6-(4-fluoro-benzyl)adenosine ( L ₈ , 8), N6-(4-methylbenzyl)adenosine ( L ₉ , 9), 2-chloro-N6-(3-hydroxy-benzyl)adenosine ( L ₁₀ , 10), 2-chloro-N6-(4-hydroxybenzyl)adenosine ( L ₁₁ , 11), 2-chloro-N6-(2-hydroxy-3-methoxybenzyl)adenosine ( L ₁₂ , 12) and 2-chloro-N6-(2-hydroxy-5-methylbenzyl)adenosine ( L ₁₃ , 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 IC ₅₀ > 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.