Hydration-coupled coordination chemistry in inorganic enzyme catalysis: from FeO d–p electronic structure to the activation field

Inorganic enzyme catalysis challenges the notion that enzymatic function strictly requires sequence-defined macromolecular active sites. Using hydrated iron oxide nanostructures as a representative model, this Review integrates peroxidase-like oxidation and phosphatase-like hydrolysis within a physicochemical framework based on two complementary principles. The Inorganic Code defines intrinsic electronic and catalytic potential rooted in transition-metal d -electron configurations and metal–ligand d–p interactions, establishing a landscape of electronically reconfigurable states. Coordination geometry, valence organization, connectivity, defects, and electron–lattice coupling determine how this potential is expressed through charge localization, redistribution, and, where electronically accessible, intersite electron hopping. An inorganic enzyme is thus conceptualized as a dynamically integrated material–interface–reactant system rather than a static nanomaterial. In hydrated mineral systems, water acts as an organizing medium through coordinated water, surface hydroxyls, hydration shells, and hydrogen-bond networks, coupling metal-centred electronic responsiveness to proton transfer, substrate coordination, bond activation, and interfacial restructuring. Peroxidase-like oxidation and phosphate-ester hydrolysis therefore share a responsive material-level framework while operating through distinct elementary mechanisms. The spatiotemporal organization–separation effect describes how electronic, protonic, hydration, molecular, structural, and chemical processes occurring at different locations and timescales remain functionally coupled, while reaction-dependent rectification of otherwise reversible or stochastic electronic dynamics through their coupling to protonic, hydration, molecular, structural, and chemical processes constitutes the electron ratchet. Under suitable nonequilibrium conditions, sustained higher-order integration may give rise to the proposed Activation Field. This systems-level framework supports recognition of inorganic enzymes as a distinct catalytic architecture alongside protein enzymes and catalytic RNA .