Effects of Cp*-Ligands in Titanocene-Based Thiosemicarbazone Complexes

Titanocene-based complexes are among the most prominent organometallic anticancer drugs. Since the discovery of titanocene dichloride, numerous derivatives have been tested as potential chemotherapeutic agents. We previously reported on titanocene-based drug carriers by using substitution-labile triflato ligands to generate cationic complexes with cytotoxic thiosemicarbazones (TSCN). Building on this, we posed the question of whether the larger cyclopentadiene derivative, pentamethylcyclopentadiene (Cp*), might further stabilize the organometallic drug carriers or provide other benefits such as increased lipophilicity. In this work, we describe the synthesis of titanocene-based complexes bearing Cp* and TSCN ligands and discuss how the Cp* ligands affect the water solubility and stability. Our findings are supported by DFT calculations, which enable a rational approach for the design of novel organometallic drug carriers.