Highly Active Antitumor Titanium(IV) Phenolato Complexes: The Influence of Structural Factors on Complex Performance

Avia Tzubery, Institute of Chemistry, Jerusalem, Israel
Edit Y. Tshuva, Institute of Chemistry, Jerusalem, Israel

The anticancer activity of the inorganic compound cisplatin and its worldwide use in the pharmaceutical industry initiated a new field of research, aimed at finding new inorganic complexes of other metals that may lead to improved anticancer drugs. Among others, Ti(IV) complexes titanocene dichloride and budotitane demonstrated high cytotoxic activity but eventually failed clinical trials due to their low hydrolytic stability. We previously introduced cytotoxic Ti(IV) complexes based on salan ligands that demonstrated high activity along with exceptional hydrolytic stability.

Herein we examine the influence of structural aspects on the complex reactivity and stability. We will present the first trans-Ti(IV) complexes of high cytotoxicity based on salen ligands.^1-2 These complexes are highly active towards various cancer cell lines, with improved hydrolytic stability relative to that of the known Ti(IV) complexes. Structure-activity relationships will be discussed. Additionally, we will present salalen-Ti(IV) complexes, which are half salan-half salen, with a fac-mer binding mode that gives a C₁ symmetry. The effect of this geometry on the properties and performance of the Ti(IV) complexes will also be addressed.

References

1.    Tzubery A., Tshuva E. Y., Inorg. Chem. 2011, 50, 7946.
2.    Tzubery A., Tshuva E.Y., Inorg. Chem. 2012, 51, 1796.