Increasing anti-cancer activity with longer tether lengths of group 9 Cp∗ complexes

Here in, we report the cytotoxicity of both rhodium and iridium functionalised Cp∗ analogues of the [Cp∗MCl₂]₂ dimers. The functionalised dimers contain a hydroxy tethered arm of differing carbon length. These show promising IC₅₀ values when tested against HT-29, A2780 and cisplatin-resistant A2780cis human cancer cell lines, with the cytotoxicity improving proportionally with an increase in carbon tether length of the Cp∗ ring. The most promising results are seen for the 14-carbon Cp∗ tethered rhodium (2d) and iridium (3b) complexes, which show up to a 24-fold increase in IC₅₀ compared to the unfunctionalised [Cp∗MCl₂]₂ dimer. All complexes were potent inhibitors of purified thioredoxin reductase suggesting that disruption of cellular anti-oxidant function is one potential mechanism of action.