Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Chemistry. 2011 Dec 9;17(50):14094-103. doi: 10.1002/chem.201102017. Epub 2011 Nov 10.
The effect of stereochemistry on the cytotoxicity of highly active and hydrolytically stable N-methylated Ti(IV) salan complexes is reported. Four bis(isopropoxo) complexes incorporating N-methylated salan ligands with different aromatic substitution patterns have been prepared in racemic and optically active forms for the first time by ligand-to-metal chiral induction from trans-diaminocyclohexyl-based chiral ligands. The configuration of the metal center that derives from that of the ligand has an enormous influence on cytotoxicity, with the racemic mixture mostly being more active than the single enantiomers that are of either similar or different activity. This implies that the active species is a salan-bound heterochiral polynuclear compound, interacting with a chiral target. Four additional complexes of achiral salan and chiral labile sec-butoxo ligands, analyzed as racemic and as homochiral, revealed no influence of stereochemistry, supporting early dissociation of the labile ligands to give the polynuclear products.
报道了立体化学对高活性和水解稳定的 N-甲基化 Ti(IV)salan 配合物的细胞毒性的影响。首次通过基于反式二氨基环己基的手性配体的配体到金属的手性诱导，以外消旋和旋光活性形式制备了四个包含具有不同芳香取代模式的 N-甲基化salan 配体的双（异丙氧基）配合物。金属中心的构型源自配体，对细胞毒性有巨大影响，外消旋混合物的活性通常比单一对映异构体的活性更高，无论活性相似或不同。这意味着活性物质是与手性靶标相互作用的salan 结合的杂手性多核化合物。另外四个无手性salan 和手性不稳定的仲丁氧基配体的配合物，作为外消旋体和同手性体进行分析，没有立体化学的影响，支持不稳定配体的早期解离以生成多核产物。
