Homometallic Polynuclear Rhodium Complexes in Anticancer Drug Development

After cisplatin discovery in anticancer treatment, many metals have been studied as potential antitumor agents, especially group IXB elements, such as rhodium, iridium, palladium, and their complexes. The design of polymetallic complexes containing different metal centers with diverse pharmacological characteristics has raised considerable interest in the field of drug development research. This approach aims to exploit the synergistic effect of distinct metal cations, which could contribute to enhancing biological activity. The basic rationale is that the combination of two or more metal ions with the same or different cytotoxic profiles and modes of action may significantly modify the anticancer potential of the resulting complexes, thus enlarging the biological targets and improving the biodistribution properties compared to mononuclear fragments. Among the reported multinuclear anticancer complexes, rhodium-based compounds have attracted considerable attention despite their relatively limited history. The current article presents the results obtained in the field of rhodium complexes, highlighting the recent advances of polynuclear homometallic rhodium compounds as promising antineoplastic candidates. While widespread studies have focused on mononuclear rhodium complexes, the potential of polynuclear Rh-based compounds with structural and functional diversity remains rather understudied. This low interest is most likely due to the typical kinetic inertness and chemical stability of most rhodium complex compounds. These complexes have garnered considerable attention due to their enhanced cytotoxic effects, intracellular distribution, and selectivity, thereby holding promising prospects for the further development of multifunctional drug candidates with desired activity. Recent developments of polynuclear rhodium-based antitumor agents have been summarized in the current review.