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 3 H) or n -BuLi, followed by transmetalation with titanium tetrachloride, to yield the corresponding titanocene dichloride derivatives. These complexes are bis-[((phenyl)dimethylsilane)cyclopentadienyl] titanium(IV) dichloride ( 3a ), bis-[((4-methoxyphenyl)dimethylsilane)cyclopentadienyl] titanium(IV) dichloride ( 3b ), bis-[((4- N, N -dimethylmethanamine)dimethylsilane)cyclopentadienyl] titanium(IV) dichloride ( 3c ), bis-[((4- N, N -diethylmethanamine)dimethylsilane)cyclopentadienyl] titanium(IV) dichloride ( 3d ), bis-[((1-methyl-5-trimethylsilyl)indol-3-yl)methylcyclopentadienyl] titanium(IV) dichloride ( 4e ), and bis-[((1-methyl-3-diethylaminomethyl-5-trimethylsilyl)indol-2-yl)methylcyclopentadienyl] titanium(IV) dichloride ( 4f ). The two titanocenes 3a and 3b 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 50 values. Titanocenes were found to have IC 50 values of 139 (±5), 106 (± 4), 127 (±4), 104 (±9), 90 (±6), and 15 (±2) μM.