Abstract
Benzyl amine was coupled to the dangling carboxylic acid groups of the platinum(II) complex [Pt(edda)Cl(2)], where edda = ethylenediamine-N,N'-diacetic acid, to give the diamidetethered complex [Pt(L)Cl(2)] (1), where L = ethylenediamine-N,N'-bis(N-benzylacetamide). Complex 1 was oxidized with both PhICl(2) and Br(2). Oxidation with PhICl(2) cleanly afforded the tetrachloride complex, [Pt(L)Cl(4)] (2), whereas oxidation with Br(2) gave rise to several mixed halide complexes of the general formula, [Pt(L)Cl(x)Br(4-x)], where x = 1, 2, or 3. Complexes 1 and 2 were fully characterized by (1)H, (13)C, and (195)Pt NMR spectroscopy, as well as by ESI-MS. These compounds exist as a mixture of diastereomers that arise from the chirality of the two coordinated nitrogen atoms. Crystal structures of 1, 2, and [Pt(L)Cl(x)Br(y)] (3) are reported. Although refined as the tetrabromide complex [Pt(L)Br(4)], the crystal structure of 3 is a mixture of species with site-occupancy disorder of chloride and bromide ligands. DFT calculations indicate that the two sets of diastereomers of 1 and 2 are effectively thermoneutral, a conclusion that is also supported by the observation of both members of each pair by NMR spectroscopy. The cytotoxicity of 1 and 2 was measured by the MTT assay in HeLa cells and compared to that of cisplatin. Both exhibit IC(50) values close to 50 μM and are therefore substantially less toxic than cisplatin, for which the IC(50) is 1 μM.