Advances in the design of organometallic anticancer complexes

Abstract

Organometallic complexes containing ligands such as CO, carbenes, alkyls, phenyls, π-bound alkynes, alkenes, cyclopentadienyls and arenes possess properties which have often been exploited in areas such as catalysis and materials chemistry. They also offer opportunities for the design of new drugs with novel mechanisms of action. Here we focus on anticancer drugs which might complement successful platinum drugs in the clinic by widening the spectrum of activity, reducing side-effects and combatting resistance. The early clinical trials of titanocene dichloride highlighted the need to understand the aqueous solution chemistry of organometallic complexes and to identify their target sites in cancer cells. More recently organometallic Cp complexes of Fe(II), Rh(III) and Ir(III), and arene complexes of Ru(II) and Os(II), have been shown to target the redox balance in cancer cells, in contrast to DNA which is the target of cisplatin and related platinum drugs. The activity of both catalytic and photoactive organometallic compounds is being explored. Target recognition and activity are highly dependent not only on the metal and its oxidation state, but also the other coordinated ligands, the coordination number and geometry. In general, organometallic complexes are ‘pro-drugs’ which undergo activation in vivo (by ligand exchange or redox reactions), and the ligands themselves may be active components of the drug. A major challenge is to elucidate the chemistry of organometallic complexes directly in cells. The design of organometallic complexes for therapeutic and diagnostic applications in cancer and other areas of medicine present new and exciting research opportunities.