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

The platinum(II) complexes trans-[PtCl2(L-n)(2)]center dot xSolv 1-13 (Solv = H2O or CH3OH), 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-methoxybenzyl) 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-fluorobenzyl) adenosine (L-8, 8), N6-(4-methylbenzyl) adenosine (L-9, 9), 2-chloro-N6-(3-hydroxybenzyl) 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 (H-1-, C-13-, Pt-195- and N-15-) 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 mu M). 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.