A novel alkenyl-substituted ansa-zirconocene complex with dual application as olefin polymerization catalyst and anticancer drug

The alkenyl substituted fulvene compound, (C₅H₄)CMe(CH₂CH₂CHCMe₂) (1), reacts with one equivalent of LiMe to give the lithium derivative Li{C₅H₄(CMe₂CH₂CH₂CHCMe₂)} (2). The reaction of 2 with Me₂Si(C₅Me₄H)Cl gave the ansa-ligand precursor Me₂Si(C₅Me₄H)(C₅H₄(CMe₂CH₂CH₂CHCMe₂)) (3), which after the subsequent reaction with 2 equivalents of LiBuⁿ yielded the dilithium salt Li₂{Me₂Si(C₅Me₄)(C₅H₃(CMe₂CH₂CH₂CHCMe₂))} (4). The alkenyl-substituted zirconocene complex Zr{Me₂Si(η⁵-C₅Me₄)(η⁵-C₅H₃(CMe₂CH₂CH₂CHCMe₂))}Cl₂] (5) was synthesized by the equimolar reaction of 4 and ZrCl₄. 5 was characterized by spectroscopic methods and by single crystal X-ray diffraction studies. The zirconocene compound 5 has been tested as a catalyst in the polymerization of ethylene at different temperatures and Al:Zr ratios, and also in the co-polymerization of ethylene and 1-octene, observing modest co-monomer incorporations. In addition, the cytotoxic activity of 5 was tested against tumour cell lines 8505C anaplastic thyroid cancer, A253 head and neck tumour, A549 lung carcinoma, A2780 ovarian cancer and DLD-1 colon carcinoma. Complex 5 showed the best cytotoxic activity on A2780 ovarian cancer (IC₅₀ value of 36.8 ± 5.9 μM). This represents the highest reported cytotoxic activity of a zirconocene complex on A2780 ovarian cancer. In addition, the cytotoxic activities of 5, have been compared with those obtained using cisplatin.