Synthesis and Cytotoxicity Studies of Fluorinated Derivatives of Vanadocene Y

From the reaction of 6-(2-fluoro-4-methoxyphenyl)fulvene (1a), 6-(3-fluoro-4-methoxyphenyl)fulvene (1b) and 6-[4-(trifluoromethoxy)phenyl]fulvene (1c) with LiBEt3H, lithiated cyclopentadienide intermediates (2a-c) were synthesised. These intermediates were then transmetallated to vanadium with VCl4 to yield the benzyl-substituted vanadocenes bis[(2fluoro-4-methoxybenzyl)cyclopentadienyl]vanadium(IV) dichloride (3a), bis[(3-fluoro-4-methoxybenzyl)cyclopentadienyl]vanadium(IV) dichloride (3b), and bis[(4-trifluoromethoxybenzyl)cyclopentadienyl]vanadium(IV) dichloride (3c). The three vanadocenes 3a-c were characterised by single-crystal X-ray diffraction. All three vanadocenes had their cytotoxicity investigated through MTT-based preliminary in-vitro testing on the LLC-PK and Caki-1 cell lines in order to determine their IC50 values. Vanadocenes 3a-c were found to have IC50 values of 6.0 (+/-4), 35 (+/-7) and 13 (+/-3) mu m on the LLC-PK cell line and IC50 values of 78 (+/-11), 18 (+/-16) and 2.2 (+/-0.5) mu m on the Caki-1 cell line respectively. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)