Engineering Adaptive Hydrogen Bond Networks in Metal–Organic Frameworks for Bioinspired H 2 O 2 Catalysis Enhancement

Dynamic hydrogen bond networks are integral to enzymatic catalysis, enabling efficient substrate polarization, intermediate stabilization, and rapid active-site turnover. However, translating such adaptive features into synthetic systems at the nanoscale presents a significant challenge. Here, we report a rationally designed Fe–containing metal–organic framework (MOF), 2,5OH-MIL-101(Fe), derived from MIL-101(Fe), that mimics enzyme-like hydrogen-bond dynamics for efficient hydrogen peroxide (H 2 O 2 ) activation. By site-specific hydroxyl functionalization of terephthalate linkers, 2,5OH-MIL-101(Fe) forms a confined hydrogen-bond network around FeO 6 centers that stabilizes H 2 O 2 -derived intermediates through O–H···O interactions and promotes O–O bond activation. This network subsequently polarizes electrons through directional hydrogen bond interactions and ultimately facilitates H 2 O desorption via reversible bond switching. These nanostructured interactions continuously regenerate Fe active sites, leading to a 94.1-fold enhancement in peroxidase-like activity compared to conventional ferroferric oxide nanoparticles. The catalyst demonstrates robust, selective, and sensitive H 2 O 2 activation within a physiologically relevant concentration range (10–1000 μM). This work demonstrates hydrogen bond network engineering in MOFs as a promising approach for creating adaptive catalysts that combine the precision of enzymes with the stability of nanomaterials, advancing bioinspired heterogeneous catalysis.