Facile synthesis of [ONON] type titanium(IV) bis-chelated complexes in alcoholic solvents and evaluation of anti-tumor activity

Novel anti-tumoral diamino-bis-(phenolato) [ONON] type titanium(IV) complexes stabilized by 2,6-dipicolinic acid were synthesis via an efficient protocol using n-propanol as solvent and H2O for isolation. In total 20 [ONON] type and 2 Salan Ti(IV) bis-chelated complexes were synthesized with yields ranging from 68% to 96%. All reactions could reach to completion in 1.5 min at 80 degrees C either using Ti(OiPr)4 or TiCl4 as starting materials. Most [ONON] type Ti(IV) complexes exhibit selectively enhanced inhibition activity against Hep G2 cells in comparison with Salan Ti(IV) complexes. Among which, the inhibitory activity of 2 t (IC50: 0.15 +/- 0.1 mu M) against Hep G2 cells is about 80 times enhanced than that of cisplatin (IC50: 12.4 +/- 1.2 mu M). The [ONON] type Ti(IV) complexes slowly released nontoxic phenolato ligands in presence of large amount of aqueous media, and a fast cellular uptake process was proposed for these Ti(IV) complexes based on metal uptake analysis. Decagram scale synthesis indicates this facile synthetic methodology can be applied to large scale synthesis.

Automated summary

Novel anti-tumoral titanium complexes have been synthesized via an efficient protocol, showing selectively enhanced inhibition activity against Hep G2 cells and the ability to slowly release nontoxic ligands in the presence of aqueous media.