Strong Cytotoxicity of Organometallic Platinum Complexes with Alkynyl Ligands

The synthesis, spectroscopy, structures, and chemical reactivity of the organometallic complexes [(COD)Pt(C CR)(2)] and [(COD)Pt(C CR)(R')] (COD = 1,5-cyclooctadiene, R = Ph, (Me)Ph (2Me, 3Me, or 4Me), (NO2)Ph (2NO(2), 3NO(2), or 4NO(2)), (4F)Ph, (4OMe)Ph, 2Py (2-pyridyl); R' = Me (methyl), Neop (neopentyl = 2,2-dimethyl-1-methyl), NeoSi (neosilyl = trimethylsilylmethyl), Bz (benzyl)) has been explored. The crystal structures reveal square-planar surroundings of the Pt atoms with short Pt-C(alkynyl) bonds (<2 angstrom) and almost perpendicular orientation of the C C-aryl group to the Pt coordination plane. Nonattractive pi-pi stacking and C-H center dot center dot center dot F intermolecular interactions were observed in the crystal structures. Multinuclear (H-1, C-13, Pt-195, and F-19) NMR spectroscopy reveals structures in solution and Pt-ligand bond strength. The thermal stability in organic solvents, the electrochemical stability, and the reactivity of the complexes in organic or aquatic (water-containing) solution toward the physiologically relevant species glutathione, chloride, and protons was tested, revealing remarkable stability or inertness of the complexes. Cytotbxicity experiments in HT-29 colon carcinoma and MCF-7 breast adenocarcinoma cell lines revealed highly promising activities for selected platinum alkynyl COD complexes.