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Fluorinated Derivatives of Titanocene Y: Synthesis and Cytotoxicity Studies
Author(s) -
Claffey James,
Gleeson Brendan,
Hogan Megan,
MüllerBunz Helge,
Wallis Denise,
Tacke Matthias
Publication year - 2008
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.200800504
Subject(s) - fulvene , chemistry , cyclopentadienyl complex , cytotoxicity , titanium , medicinal chemistry , hydride , stereochemistry , organic chemistry , metal , in vitro , catalysis , biochemistry
From the reaction of Super Hydride (LiBEt 3 H) with 6‐(2‐fluoro‐4‐methoxyphenyl)fulvene ( 1a ), 6‐(4‐trifluoromethoxyphenyl)fulvene ( 1b ), and 6‐(3‐fluoro‐4‐methoxyphenyl)fulvene ( 1c ) lithiated cyclopentadienide intermediates 2a – c were synthesised. These intermediates were then transmetallated to titanium with TiCl 4 to give the benzyl‐substituted titanocenes bis[(2‐fluoro‐4‐methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride ( 3a ), bis[(4‐trifluoromethoxybenzyl)cyclopentadienyl]titanium(IV) dichloride ( 3b ) andbis[(3‐fluoro‐4‐methoxybenzyl)cyclopentadienyl]titanium(IV)dichloride ( 3c ). The three titanocenes 3a – c were characterised by single‐crystal X‐ray diffraction. Preliminary in vitro cell tests were performed on the titanocenes on the LLC‐PK (long‐lasting cells–pig kidney) cell line in order to determine the cytotoxicity of these compounds presented in this paper. The titanocenes 3a and 3b had their cytotoxicity inhibitory concentration (IC 50 ) values determined to be 6.0 and 7.3 μ M , respectively. The cytotoxicity value of 3c could not be determined accurately due to solubility problems of the compound under standard test conditions. All three titanocene derivatives show significant cytotoxicity improvement when compared to unsubstituted titanocene dichloride, whereas titanocenes 3a and 3b show threefold cytotoxicity improvement in comparison to previous class leader titanocene Y. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)