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

The alkenyl substituted fulvene compound, (C(5)H(4))=CMe(CH(2)CH(2)CH=CMe(2)) (1), reacts with one equivalent of LiMe to give the lithium derivative Li{C(5)H(4)(CMe(2)CH(2)CH(2)CH=CMe(2))} (2). The reaction of 2 with Me(2)Si(C(5)Me(4)H)Cl gave the ansa-ligand precursor Me(2)Si(C(5)Me(4)H)(C(5)H(4)(CMe(2)CH(2)CH(2)CH=CMe(2))) (3), which after the subsequent reaction with 2 equivalents of LiBun yielded the dilithium salt Li(2){Me(2)Si(C(5)Me(4))(C(5)H(3)(CMe(2)CH(2)CH(2)CH=CMe(2)))} (4). The alkenyl-substituted zirconocene complex [Zr{Me(2)Si(g(5)-C(5)Me(4))(g5-C(5)H(3)(CMe(2)CH(2)CH(2)CH@ CMe2))}Cl(2)] (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 (IC(50) value of 36.8 +/- 5.9 mu M). 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. (C) 2009 Elsevier B. V. All rights reserved.