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 (LiBEt3H) 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 IC50 values. Titanocenes were found to have IC50 values of 139 (±5), 106 (± 4), 127 (±4), 104 (±9), 90 (±6), and 15 (±2) μM.

已分离并表征了六种新型二茂钛（titanocene）化合物。本研究以硅基取代的富烯或环戊二烯为前体，通过超氢化物（Super Hydride，LiBEt3H）或正丁基锂（n-BuLi）引发反应，随后与四氯化钛发生金属转移反应，成功合成得到六种对应的二氯化二茂钛衍生物，分别为：双-[((苯基)二甲基硅基)环戊二烯基]钛(IV)二氯化物（3a）、双-[((4-甲氧基苯基)二甲基硅基)环戊二烯基]钛(IV)二氯化物（3b）、双-[((4-N,N-二甲基甲胺基)二甲基硅基)环戊二烯基]钛(IV)二氯化物（3c）、双-[((4-N,N-二乙基甲胺基)二甲基硅基)环戊二烯基]钛(IV)二氯化物（3d）、双-[((1-甲基-5-三甲基硅基)吲哚-3-基)甲基环戊二烯基]钛(IV)二氯化物（4e）以及双-[((1-甲基-3-二乙基氨甲基-5-三甲基硅基)吲哚-2-基)甲基环戊二烯基]钛(IV)二氯化物（4f）。其中化合物3a与3b已通过X射线单晶衍射（X-ray crystallography）完成结晶结构表征；针对全部六种二茂钛化合物，本研究采用基于MTT法的体外实验针对CAKI-1细胞系开展细胞毒性测试，以测定其半数抑制浓度（IC50）值。测试结果表明，六种化合物的IC50值依次为139(±5)、106(±4)、127(±4)、104(±9)、90(±6)及15(±2) μM。