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Artificial metalloenzymes (ArMs) can combine the unique features of both metal complexes and enzymes by incorporating a cofactor within a protein scaffold. Herein, we describe a panel of ArMs constructed by covalently linking Ir( iii ) polypyridyl complexes into a prolyl oligopeptidase scaffold. Spectroscopic methods were used to examine how properties of the resulting ArMs are influenced by structural variation of the cyclometalated ligands and the protein scaffold. Visible light photocatalysis by these hybrid catalysts was also examined, leading to the finding that they catalyze inter/intra-molecular [2 + 2] photocycloaddition in aqueous solution. Low but reproducible enantioselectivity was observed using a cofactor that undergoes partial kinetic resolution upon bioconjugation within the ArM active site, showing the importance of scaffold/cofactor interactions for enabling selective ArM photocatalysis. Further evidence of the importance of cofactor/scaffold interactions was provided by analyzing native POP peptidase catalysis by the ArMs. Together, these studies show how Ir( iii )-based ArMs constitute a promising starting point for ongoing studies to control the stereoselectivity of EnT reactions by engineering substrate binding/activation motifs in POP. 

Visible light photocatalysis enables a broad range of organic transformations that proceed via single electron or energy transfer. Metal polypyridyl complexes are among the most commonly employed visible light photocatalysts. The photophysical properties of these complexes have been extensively studied and can be tuned by modifying the substituents on the pyridine ligands. On the other hand, ligand modifications that enable substrate binding to control reaction selectivity remain rare. Given the exquisite control that enzymes exert over electron and energy transfer processes in nature, we envisioned that artificial metalloenzymes (ArMs) created by incorporating Ru( ii ) polypyridyl complexes into a suitable protein scaffold could provide a means to control photocatalyst properties. This study describes approaches to create covalent and non-covalent ArMs from a variety of Ru( ii ) polypyridyl cofactors and a prolyl oligopeptidase scaffold. A panel of ArMs with enhanced photophysical properties were engineered, and the nature of the scaffold/cofactor interactions in these systems was investigated. These ArMs provided higher yields and rates than Ru(Bpy) 3 2+ for the reductive cyclization of dienones and the [2 + 2] photocycloaddition between C -cinnamoyl imidazole and 4-methoxystyrene, suggesting that protein scaffolds could provide a means to improve the efficiency of visible light photocatalysts.