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

Abstract

The alkenyl substituted fulvene compound, (C 5H 4) CMe(CH 2CH 2CH CMe 2) ( 1), reacts with one equivalent of LiMe to give the lithium derivative Li{C 5H 4(CMe 2CH 2CH 2CH CMe 2)} ( 2). The reaction of 2 with Me 2Si(C 5Me 4H)Cl gave the ansa-ligand precursor Me 2Si(C 5Me 4H)(C 5H 4(CMe 2CH 2CH 2CH CMe 2)) ( 3), which after the subsequent reaction with 2 equivalents of LiBu n yielded the dilithium salt Li 2{Me 2Si(C 5Me 4)(C 5H 3(CMe 2CH 2CH 2CH CMe 2))} ( 4). The alkenyl-substituted zirconocene complex [Zr{Me 2Si(η 5-C 5Me 4)(η 5-C 5H 3(CMe 2CH 2CH 2CH CMe 2))}Cl 2] ( 5) was synthesized by the equimolar reaction of 4 and ZrCl 4. 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 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.