Oxidative Reactivity and Cytotoxic Properties of a Platinum(II) Complex Prepared by Outer-Sphere Amide Bond Coupling.
Benzyl amine was coupled to the dangling carboxylic acid groups of the platinum(II) complex [Pt(edda)Cl2], where edda = ethylenediamine-N,N'-diacetic acid, to give the diamidetethered complex [Pt(L)Cl2] (1), where L = ethylenediamine-N,N'-bis(N-benzylacetamide). Complex1was oxidized with both PhICl2and Br2. Oxidation with PhICl2cleanly afforded the tetrachloride complex, [Pt(L)Cl4] (2), whereas oxidation with Br2gave rise to several mixed halide complexes of the general formula, [Pt(L)ClxBr4-x], where x = 1, 2, or 3. Complexes1and2were fully characterized by1H,13C, and195Pt 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 of1,2, and [Pt(L)ClxBry] (3) are reported. Although refined as the tetrabromide complex [Pt(L)Br4], the crystal structure of3is a mixture of species with site-occupancy disorder of chloride and bromide ligands. DFT calculations indicate that the two sets of diastereomers of1and2are effectively thermoneutral, a conclusion that is also supported by the observation of both members of each pair by NMR spectroscopy. The cytotoxicity of1and2was measured by the MTT assay in HeLa cells and compared to that of cisplatin. Both exhibit IC50values close to 50 μM and are therefore substantially less toxic than cisplatin, for which the IC50is 1 μM.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Justin J
JJ
Wilson
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Stephen J
SJ
Lippard
MTT assay; NMR spectroscopy; X-ray crystallography; amide coupling; cisplatin; platinum