Multinuclear Ruthenium Sites Confined in Metal–Organic Frameworks with Bio-Inspired Water Networks for Efficient Water Oxidation

Natural enzymes achieve exceptional catalytic efficiency by organizing substrates within precisely defined microenvironments, a level of control that remains challenging to replicate in synthetic systems. Here we report an enzyme-inspired strategy in which a mononuclear Ru-cba water-oxidation catalyst is assembled into a Hf-based MOF to form Hf-Ru-cba featuring confined catalytic pockets and spatially organized multinuclear Ru-cba sites (cba = 5,5'-bis(4-carboxyphenyl)-[2,2'-bipyridine]-6,6'-dicarboxylic acid). Within these nanocavities, an extended hydrogen-bond network preorganizes water molecules and stabilizes high-valent intermediates, thereby accelerating the water-nucleophilic-attack (WNA) pathway. This microenvironment-driven enhancement yields a turnover frequency of 20.6 s^-1, which is nearly an order of magnitude higher than that of the discrete Ru-cba analogue. Furthermore, the MOF-integrated catalyst maintains its exceptional activity even at an ultralow catalyst concentration (3.6 μM) compared with the homogeneous system. Mechanistic evidence from kinetics, isotope labeling, and DFT calculations confirms that nanoconfinement directs the reaction toward a WNA mechanism and lowers the barrier for O-O bond formation. The heterogeneous Hf-Ru-cba catalyst also exhibits excellent operational stability, retaining performance over at least five cycles. These results establish MOFs as programmable scaffolds for integrating molecular catalysts and highlight water-network engineering as a powerful approach to modulate reaction dynamics.