Electrochemical Study of Highly Substituted Titanocene Dihalides

Titanocene dihalides are promising alternative to Cisplatin in cancer chemotherapy which should reduce negative side effects and overcome increasing resistance of cancer cells. Since the mechanism of anti-cancer action is associated with generation of reactive oxygen species (ROS), hence with redox processes, electrochemical investigation of titanocene species would be an important issue, not applied up to now. In this article we report on the electrochemical reduction as well as oxidation of titanocene difluorides and dichlorides where unsubstituted as well as highly substituted titanocene dihalides are compared. The experiments were realized in acetonitrile using various electrode materials. The studied series was completed by a new dimethylsilylene bridged ansa-titanocene difluoride which was characterized by NMR and x-ray crystallography. The influence of structure and substitution on the redox properties was evaluated and, in addition to this, cytotoxicity of studied titanocene dihalides against human ovarian cancer cell lines A2780 and SK-OV-3, as well as against human embryonic kidney cell line HEK293 were screened. Two of highly substituted titanocenes exhibit cytotoxicity comparable with that of Cisplatin.