Ether-Substituted Group 4 Metallocene Complexes: Cytostatic Effects and Applications in Ethylene Polymerization

The synthesis of the ether-substituted group 4 metallocene complexes [Ti­(η5-C5H5)­(η5-C5H4{CMeRCH­(OMe)2})­Cl2] (R = Me (4), Ph (5)) and [M­(η5-C5H4{CMeRCH­(OMe)2})2Cl2] (M = Ti, R = Me (6), Ph (7); M = Zr, R = Me (8), Ph (9)) is reported. In addition, the titanocene derivatives 4–7 have been supported on the mesoporous silica-based material KIT-6, giving the functionalized materials K4–K7, respectively. All compounds and materials have been characterized by different analytical techniques such as solution NMR spectroscopy, mass spectrometry, elemental analysis, solid-state multinuclear NMR spectroscopy, IR spectroscopy, N2 adsorption–desorption isotherms, X-ray fluorescence and diffraction, SEM, and TEM. Additionally, the molecular structures of the zirconocene derivative 8 and the hydrolysis product [Ti­(η5-C5H5)­(η5-C5H4{CMe2COO})­Cl] (4a) of titanocene complex 4 have been determined by X-ray diffraction studies. The structure of 4a reveals a five-membered metallacyclic arrangement. The ether-substituted titanocene compounds 4–6 and the functionalized material K5 have been tested for their antiproliferative and cytotoxic effects in vitro in three human cancer cell lines (A549 lung adenocarcinoma, MCF-7 breast adenocarcinoma, and HCT-116 colorectal adenocarcinoma), as well as in normal human fibroblasts. Compounds 4–6 and K5 showed moderate but specific cytostatic effects. Moreover, additional studies related to the hydrolytic stability (for 4–7) and DNA interaction (for 6) have been carried out. Finally, taking into account the feasible applicability of metallocene complexes, a preliminary ethylene polymerization study has been performed using the two synthesized zirconocene compounds (8 and 9).