Antitumor Ti(IV) Complexes Based on Salen Ligand: Fluorescence Properties for Cell Imaging

Titanium(IV) complexes are highly attractive candidates for anticancer treatments due to their high antitumoral features and low toxicity of their final hydrolysis product titanium dioxide. Accordingly, titanium complexes titanocene dichloride and budotitane were the first to enter clinical trials after platinum complexes. These compounds showed promising results but eventually failed due to their low hydrolytic stability in biological environment that led to undefined aggregates with low solubility, hampering mechanistic investigations. We have introduced Ti(IV) complexes with phenolato ligands that presented exceptional hydrolytic stability, combined with high cytotoxicity. In particular, Ti(IV) complexes based on salen ligands showed promising result with high activity and improved stability and solubility in relevant biological solvents.^1,2 Salen ligands, salicylaldehyde based bis-shiff bases with different conjugated amine bridges, could be also functionalized by a various electron accepting and donating subtituents, to present well tuned photophysial properties for various applications.

Herein we present the design of Ti(IV) salen complexes that along with their high activity and stability, could function as fluorophores for living cell imaging. The salen ligands can be modified to include different subtituents on the phenolato and the anime moieties of the salen ligand, which could enhance their fluorescence. Moreover, the salen ligands bind equatorially to the Ti(IV) center, enhancing the ligand planarity and contributing to π-conjugation. This photophysial property of the salen Ti(IV) complexes may be utilized to add new information on cellular integrations and biological target of the Ti(IV) complexes.

(1) Tzubery, A., and Tshuva, E. Y. Inorg. Chem. (2011) 50, 7946–7948.

(2) Tzubery, A., and Tshuva, E. Y. Inorg. Chem. (2012) 51, 1796–1804.