Abstract

Platinum complexes are the most widely used anticancer drugs. We are investigating the design of anticancer agents of other precious metals that might be effective against a wider range of cancers, have less side effects, a different mechanism of action, and therefore be effective against platinum-resistant cancers.

I will describe our research on low-spin d6 complexes of ruthenium, osmium, iridium and platinum. The activation of these inert complexes in cells can be controlled by the choice of the ligands and by irradiation with light. Attack on DNA can be switched to perturbation of the redox balance in cancer cells. Organometallic transfer hydrogenation catalysts induce both oxidative and reductive stress. We are adopting a systems pharmacology approach to elucidating mechanisms of action using genomic, transcriptomic and proteomic screening. Unexpectedly, our work on complexes encapsulated in polymer micelles for drug delivery has led to the observation of single metal atom dynamics.