Synthesis and Cytotoxicity Studies of Silyl-Substituted Titanocene Dichloride Derivatives

Six new titanocene compounds have been isolated and characterized. These compounds were synthesized from their silyl-substituted fulvene or cyclopentadiene precursors using Super Hydride (LiBEt<sub>3</sub>H) or <i>n</i>-BuLi, followed by transmetalation with titanium tetrachloride, to yield the corresponding titanocene dichloride derivatives. These complexes are bis-[((phenyl)­dimethylsilane)­cyclopentadienyl] titanium­(IV) dichloride (<b>3a</b>), bis-[((4-methoxyphenyl)­dimethylsilane)­cyclopentadienyl] titanium­(IV) dichloride (<b>3b</b>), bis-[((4-<i>N</i>,<i>N</i>-dimethylmethanamine)­dimethylsilane)­cyclopentadienyl] titanium­(IV) dichloride (<b>3c</b>), bis-[((4-<i>N</i>,<i>N</i>-diethylmethanamine)­dimethylsilane)­cyclopentadienyl] titanium­(IV) dichloride (<b>3d</b>), bis-[((1-methyl-5-trimethylsilyl)­indol-3-yl)­methylcyclopentadienyl] titanium­(IV) dichloride (<b>4e</b>), and bis-[((1-methyl-3-diethylaminomethyl-5-trimethylsilyl)­indol-2-yl)­methylcyclopentadienyl] titanium­(IV) dichloride (<b>4f</b>). The two titanocenes <b>3a</b> and <b>3b</b> were crystallized and characterized by X-ray crystallography, while all six titanocenes were tested for their cytotoxicity through MTT-based in vitro tests on CAKI-1 cell lines in order to determine their IC<sub>50</sub> values. Titanocenes were found to have IC<sub>50</sub> values of 139 (±5), 106 (± 4), 127 (±4), 104 (±9), 90 (±6), and 15 (±2) μM.