Node-Assisted Photoredox Reactivity Enables MOF-Catalyzed Hydrogen/Deuterium Exchange in Aromatic Aldehydes

Light-driven isotopic labeling is currently dominated by homogeneous catalysis and largely relies on separate thiol-based hydrogen-atom-transfer catalysts. Metal-organic frameworks (MOFs), with their modular structures, confined pore environments, and tunable optoelectronic properties, offer an attractive but largely unexplored heterogeneous platform for controlled isotopic incorporation in chemicals. Herein, we report a systematic investigation of MOF-photocatalyzed hydrogen/deuterium (H/D) exchange, demonstrating that UiO-66-type materials uniquely enable thiol-free, formyl-selective deuteration of aromatic aldehydes using D2O as the sole deuterium source. Under UV irradiation, UiO-66 materials achieve up to 97% H/D incorporation over 3 h with 99% product selectivity, a level of control far surpassing that of catalyst-free photochemistry. Evaluation of the influence of linker functionalization shows that efficiency depends on multiple interdependent parameters, including radical generation, porosity, substrate binding and diffusion, and D2O accessibility, thereby establishing it as a key design handle for controlling reactivity in H/D exchange. Mechanistic investigations using electron paramagnetic resonance spectroscopy, controls using isotopically enriched UiO-66 and zirconium oxo clusters, and density functional theory analysis demonstrate that the Zr6O4(OH)4 nodes actively participate in catalysis, enabling deuterium transfer via proton-coupled electron-transfer mechanisms involving in situ-generated μ3-OD groups. Aldehyde confinement at the Zr6-cluster surface suppresses competing oxidation pathways and promotes a surface-confined radical mechanism that is inaccessible to homogeneous photocatalysts. Our findings establish UiO-66 as a single-component heterogeneous photocatalyst for selective isotopic labeling and mechanistically probe a previously unexplored mode of node-centered photoreactivity in MOFs. This work provides mechanistic insights into the use of MOFs for isotopic labeling and late-stage functionalization under mild conditions, highlighting the role of node-centered photochemistry.