Strong Cytotoxicity of Organometallic Platinum Complexes with Alkynyl Ligands

The synthesis, spectroscopy, structures, and chemical reactivity of the organometallic complexes [(COD)­Pt­(CCR)<sub>2</sub>] and [(COD)­Pt­(CCR)­(R′)] (COD = 1,5-cyclooctadiene, R = Ph, (Me)­Ph (2Me, 3Me, or 4Me), (NO<sub>2</sub>)­Ph (2NO<sub>2</sub>, 3NO<sub>2</sub>, or 4NO<sub>2</sub>), (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 Å) and almost perpendicular orientation of the CC–aryl group to the Pt coordination plane. Nonattractive π–π stacking and C–H···F intermolecular interactions were observed in the crystal structures. Multinuclear (<sup>1</sup>H, <sup>13</sup>C, <sup>195</sup>Pt, and <sup>19</sup>F) 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. Cytotoxicity experiments in HT-29 colon carcinoma and MCF-7 breast adenocarcinoma cell lines revealed highly promising activities for selected platinum alkynyl COD complexes.