CHAPTER 2:Ruthenium, Osmium and Iridium in the Fight Against Cancer

Abstract

DNA-targeting chemotherapeutic agents are widely used in cancer treatment. However, high incidence of resistance and deleterious side effects are still a challenging medical issue. Novel complexes based on precious metals are being developed as viable alternatives, with the aim of overcoming resistance and minimising unwanted side effects. This chapter looks at complexes with ruthenium, osmium and iridium metal centres. These complexes exhibit a wide range of structural variances that allow for the fine-tuning of chemical and biological properties. Within this chemical space, this chapter explores the importance of different building blocks in relevant coordination spheres, paying particular attention to structures such as organometallic piano-stools and other octahedral coordination motifs. It further examines some of the most prominent aspects of the mechanisms of action responsible for the antiproliferative activity of the complexes, with special focus on mechanisms that are redox centred and those that involve, to some degree, modifications of mitochondrial function. It concludes with some of the physicochemical challenges faced when looking into the mechanism of action of metal-based drugs at the cellular level. Furthermore, it provides examples of how novel analytical techniques are helping to generate new knowledge on localisation, activation and general subcellular behaviour of metal complexes.