Synthesis, structure and biological activity of amide-functionalized titanocenyls: Improving their cytotoxic properties

Nine amide-functionalized titanocenyls have been synthesized and characterized by spectroscopic and analytical methods and the solid state structure of Cp(CpCO-NH-C6H4-OCF3)TiCl2 was determined by single crystal X-ray diffraction. X-ray analysis of Cp(CpCO-NH-C6H4-OCF3)TiCl2 showed that titanium is in a pseudo tetrahedral geometry and contains a Ti–O(amide) coordination. In principle, Ti–O coordination should provide more hydrolytic stability to the corresponding titanocenyls than titanocene dichloride. The cytotoxic activities of these amide-functionalized titanocenyls on HT-29 colon cancer cell line were determined by MTT assay to elucidate structure-activity relationship. All complexes were more cytotoxic than titanocene dichloride and there is no correlation between the para substituents on the phenyl ring and their cytotoxicities.