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 2O or CH 3OH), 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 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.