TY - JOUR
T1 - Cytotoxic titanium(IV) complexes of chiral diaminobis(phenolato) ligands
T2 - Better combination of activity and stability by the bipyrrolidine moiety
AU - Miller, Maya
AU - Tshuva, Edit Y.
PY - 2014/3
Y1 - 2014/3
N2 - Racemic and enantiomerically pure titanium(IV) complexes with ortho-bromo-para-methyl-substituted diaminobis(phenolato) ligands were prepared with NH-, NMe-, and bipyrrolidine-based diamino bridges through ligand-to-metal chiral induction. The hydrolytic stability of the complexes was evaluated, and their cytotoxicity was measured using HT-29 human colon cancer cells based on the MTT assay. All stereochemical forms of the NMe-based complexes, although demonstrating the highest hydrolytic stability, were biologically inactive. For the NH and bipyrrolidine-based active complexes, the pure enantiomers exhibited high cytotoxicity whereas the racemic mixtures were inactive, supporting the involvement of a polynuclear active species. The bipyrrolidine complexes appear to provide the best combination of hydrolytic stability and biological activity, presumably by minimizing steric bulk and consequently enabling biological accessibility. Racemic and optically pure phenolato titanium(IV) complexes were prepared with NH, NMe, and bipyrrolidine-based diamino bridges. The optically pure bipyrrolidine complexes provide the best combination of hydrolytic stability and biological activity, presumably by maintaining small enough steric bulk to enable biological accessibility.
AB - Racemic and enantiomerically pure titanium(IV) complexes with ortho-bromo-para-methyl-substituted diaminobis(phenolato) ligands were prepared with NH-, NMe-, and bipyrrolidine-based diamino bridges through ligand-to-metal chiral induction. The hydrolytic stability of the complexes was evaluated, and their cytotoxicity was measured using HT-29 human colon cancer cells based on the MTT assay. All stereochemical forms of the NMe-based complexes, although demonstrating the highest hydrolytic stability, were biologically inactive. For the NH and bipyrrolidine-based active complexes, the pure enantiomers exhibited high cytotoxicity whereas the racemic mixtures were inactive, supporting the involvement of a polynuclear active species. The bipyrrolidine complexes appear to provide the best combination of hydrolytic stability and biological activity, presumably by minimizing steric bulk and consequently enabling biological accessibility. Racemic and optically pure phenolato titanium(IV) complexes were prepared with NH, NMe, and bipyrrolidine-based diamino bridges. The optically pure bipyrrolidine complexes provide the best combination of hydrolytic stability and biological activity, presumably by maintaining small enough steric bulk to enable biological accessibility.
KW - Anticancer agents
KW - Chiral induction
KW - Cytotoxicity
KW - Hydrolysis
KW - Titanium
UR - http://www.scopus.com/inward/record.url?scp=84897856124&partnerID=8YFLogxK
U2 - 10.1002/ejic.201301463
DO - 10.1002/ejic.201301463
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AN - SCOPUS:84897856124
SN - 1434-1948
SP - 1485
EP - 1491
JO - European Journal of Inorganic Chemistry
JF - European Journal of Inorganic Chemistry
IS - 9
ER -