Unexpected influence of stereochemistry on the cytotoxicity of highly efficient Ti(IV) salan complexes: new mechanistic insights

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 optica...

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Bibliographic Details
Published in:Chemistry : a European journal 2011-12, Vol.17 (50), p.14094-14103
Main Authors: Manna, Cesar M, Armony, Gad, Tshuva, Edit Y
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Humans
Hydrolysis
Ligands
Models, Molecular
Molecular Structure
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Stereoisomerism
Titanium - chemistry
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Summary: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.
ISSN:1521-3765
DOI:10.1002/chem.201102017