Controlling platinum, ruthenium, and osmium reactivity for anticancer drug design

Abstract

Publisher Summary Transition-metal complexes provide enormously versatile platforms for drug design. Many variations in the metal itself, the types, and numbers of coordinated ligands and hence in the strengths of coordination bonds and in the kinetics of ligand-substitution processes are available. This chapter discusses the efforts towards the development of photoactive platinum anticancer agents and the ruthenium– and osmium–arene families of anticancer agents. The key to successful design of clinically useful drugs is effective activity while minimizing side effects. Both the thermodynamics and kinetics of ligand-exchange and redox processes must be carefully controlled. Such control is possible by systematic ligand variation. This way, photoactive platinum(IV) complexes can be designed that are stable and nontoxic in the dark. The strategy of activation by light to yield highly cytotoxic species at irradiated spots only allows for local, targeted treatment and holds the promise of less-invasive chemotherapy. Similarly, the work on the ruthenium– and osmium–arenes showed that thermodynamic and kinetic parameters, such as those associated with aquation, can vary over several orders of magnitude, thus allowing the chemist to fine-tune the properties of the agent for increased cytotoxicity.