Charge Transfer Engineering in Covalent Organic Frameworks for Red Visible Light-Driven Coenzyme Interconversion

Precise photocatalytic modulation of the NAD+/NADH redox balance is critical for advancing both biocatalytic cascade reactions and photodynamic therapy, yet this goal remains elusive due to the scarcity of efficient, broad-spectrum photocatalysts with orthogonal redox regulation capabilities. Herein, we report a bifunctional covalent organic framework-polyoxometalate (COF-POM) composite that enables bidirectional photocatalytic interconversion between NAD+ and NADH under red visible light irradiation, achieving 77.0% yield for NADH regeneration and nearly quantitative conversion in NADH oxidation. Strikingly, cyt c-mediated anaerobic NADH oxidation was successfully realized, enabling spatiotemporally precise modulation of the intracellular NAD+/NADH redox balance. Mechanistic investigations reveal that POM integration synergistically reinforces the built-in electric field of the COF matrix, substantially accelerating photogenerated charge separation and interfacial transfer kinetics. This work establishes a generalizable strategy for constructing high-performance photocatalysts to enable precise NAD+/NADH redox balance regulation for future tumor metabolic intervention.