Preparation, structural characterization and cytotoxicity of hydrolytically stable Ti(IV) citrate complexes

Hydrolytically stable and water soluble Ti(IV) complexes can be used for various applications, including industrial, medicinal and more. Herein, a novel tetra-nuclear Ti(IV) complex with citrate ligands was obtained by reacting Ti(IV) isopropoxide and citric acid in an aqueous solution. The three dimensional structure of the complex [Ti4O6(Hcit)3(cit)]9− 1, as it appears in the compound [Co(NH3)6]3[Ti4O6(Hcit)3(cit)]⋅20H2O was determined by single-crystal X-ray crystallography. Complex 1 possesses an adamantane-like {Ti4O6} core where each metal atom is coordinated to a tri-dentate citrate ligand with one dangling CH2COOH group. An additional already known Ti(IV) complex [Ti(Hcit3−)3]5− 2 was synthesized for comparison. The high hydrolytic stability of complexes 1 and 2 has been substantiated based on NMR techniques. The cytotoxicity of the complexes was tested on three cancer cell lines: human ovarian A2780 and drug-resistant variants A2780cis and A2780ADR. Complex 1 showed a slight cytotoxicity towards the ovarian cells, while complex 2 was inactive.