Approaches to the design of catalytic metallodrugs

Metal ions are known to act as catalytic centres in metallo-enzymes. On the other hand, low-molecular-weight metal complexes are widely used as catalysts in chemical systems. However, small catalysts do not have a large protein ligand to provide substrate selectivity and minimize catalyst poisoning. Despite the challenges that the lack of a protein ligand might pose, some success in the use of metal catalysts for biochemical transformations has been reported. Here, we present a brief overview of such reports, especially involving catalytic reactions in cells. Examples include C-C bond formation, deprotection and functional group modification, degradation of biomolecules, and redox modulation. We discuss four classes of catalytic redox modulators: photosensitizers, superoxide dismutase mimics, thiol oxidants, and transfer hydrogenation catalysts. Catalytic metallodrugs offer the prospect of low-dose therapy and a challenging new design strategy for future exploration.