Cytotoxic titanium salan complexes: surprising interaction of salan and alkoxy ligands

Chemistry : a European Journal
Timo A ImmelThomas Huhn

Abstract

The synthesis, biochemical evaluation, and hydrolysis studies of a wide selection of alkyl- and halogen-substituted titanium salan alkoxides are presented herein. A systematic change in the employed alkoxides revealed that both the bulk of the salan ligands and the steric demand of the labile ligands are of great importance for the obtained biological activity. Surprisingly, these two factors are not independent from each other; lowering the steric demand of the alkoxide of a hitherto nontoxic complex renders it cytotoxic. Therefore, our data suggest that the overall size of the complex exerts a strong influence on its biological activity. To decide whether the correlation between the cytotoxicity and the steric demand of the whole complex is merely based on an altered hydrolysis or on the interaction with biomolecules, the behavior of selected complexes under hydrolytic conditions and the influence of transferrin were investigated. Complexes differing only in their labile alkoxy ligands gave the same hydrolysis products with similar hydrolysis rates but displayed cytotoxicities that differed in the range of one order of magnitude. Thus, it seems that the hydrolysis product is not the active species but rather that the unhydrol...Continue Reading

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Citations

Mar 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Arthur D TinocoAnn M Valentine
Oct 17, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sigalit MekerEdit Y Tshuva
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May 30, 2021·Journal of Inorganic Biochemistry·Gilad NahariEdit Y Tshuva
May 14, 2017·Journal of the American Society for Mass Spectrometry·Rahel P EberleStefan Schürch

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