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).