Anticancer iridium(III) cyclopentadienyl complexes

Abstract

Platinum-based anticancer drugs have been highly effective in treating various cancers. While they have shown significant promise, their potential limitations have motivated researchers to explore other noble metal-based compounds, including iridium (Ir) complexes. Among these, half-sandwich Ir(III) cyclopentadienyl (Ir–Cpx) complexes have emerged as promising new anticancer compounds. This relatively new area of bioinorganic chemistry has made significant progress since its inception in 2007, although no representative has yet entered clinical trials. Recent studies over the past 5–10 years have significantly advanced our understanding of the stability, speciation, intracellular localization, target organelles and molecular targets involved in the mechanisms of action (MoA) of these compounds. This comprehensive review provides the reader with an overview of anticancer Ir–Cpx complexes and diverse chemical, biochemical and biological methods used for their research and development. Structure-activity relationships (SAR) and mechanisms of action (MoA) are discussed with respect to anticancer activity and in comparison to their structurally similar ruthenium(II), rhodium(III) and osmium(II) analogues. Considerable attention is paid to in vivo anticancer activity and related aspects, such as drug delivery strategies, multi-component drugs or photodynamic therapy.