Green-Box-Based Supramolecular Artificial Cofactor for Visible-Light-Driven Asymmetric Photo-enzyme Catalysis

Photo-enzyme catalytic systems integrate photocatalysis, electron transfer, and enzymatic transformations; however, their overall efficiency is often limited by the spatial separation of active components, which prevents the compact architectures analogous to the “Z-scheme” in photosynthesis. Here, we report a supramolecular artificial cofactor (<b>SeV–Rh–Box⊃NAD</b>^<b>+</b>) via host–guest interactions between a selenoviologen-based tetracationic cyclophane (Green Box derivative, <b>SeV–Rh–Box</b>) and NAD⁺. When paired with alcohol dehydrogenase, this artificial cofactor forms an integrated photo-enzyme catalytic system capable of visible-light-driven asymmetric synthesis of chiral bioactive molecules. The system exhibits high catalytic performance, with enantiomeric excesses exceeding 87% and turnover numbers surpassing 47,700, maintaining over 50% catalytic efficiency after 24 h and 8 reaction cycles. The supramolecular architecture promotes intramolecular directional electron transfer to a rhodium catalytic site, thereby enhancing enzyme cofactor regeneration under light irradiation. Transient absorption and electrochemical analyses confirm efficient photoinduced electron transfer and redox cycling. This work presents a modular strategy to bridge photocatalysis and biocatalysis through supramolecular self-assembly, offering a generalizable platform for light-powered asymmetric synthesis.