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

The platinum(II) complexes trans-[PtCl(2)(L(n))(2)]∙xSolv 1–13 (Solv = H(2)O or CH(3)OH), 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 ((1)H-, (13)C-, (195)Pt- and (15)N-) 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.