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 (2NO2, 3NO2, or 4NO2), (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 (1H, 13C, 195Pt, and 19F) 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.本研究系统探究了有机金属配合物[(COD)Pt(C≡CR)₂]与[(COD)Pt(C≡CR)(R′)]的合成、光谱表征、晶体结构及化学反应活性。其中，1,5-环辛二烯(1,5-cyclooctadiene，COD)为配体；取代基R可选苯基(Ph)、取代苯基[(Me)Ph：2-Me、3-Me或4-Me；(NO₂)Ph：2-NO₂、3-NO₂或4-NO₂；4-F-Ph、4-OMe-Ph]、2-吡啶基(2Py)；取代基R′可选甲基(Me)、新戊基(Neop，即2,2-二甲基丙基)、新硅基(NeoSi，即三甲基硅基甲基)、苄基(Bz)。晶体结构解析结果显示，铂原子呈现平面四配位环境，Pt-炔基碳键长较短；通过¹H、¹³C、¹⁹⁵Pt及¹⁹F核磁共振(Nuclear Magnetic Resonance, NMR)光谱表征，可明确配合物在溶液中的结构以及Pt与配体间的键合强度。本研究测试了该类配合物在有机溶剂中的热稳定性、电化学稳定性，以及在有机或水相（含水）溶液中与生理相关物种——谷胱甘肽、氯离子及质子——的反应活性，结果显示该类配合物具有优异的稳定性或化学惰性。针对HT-29结肠癌细胞系与MCF-7乳腺癌细胞系开展的细胞毒性实验表明，所选炔基铂基COD配合物展现出极具应用前景的抗肿瘤活性。