A Solid‐State Crystallization Strategy for Direct Enzyme Encapsulation in Zr‐MOFs: Eliminating Harsh pH and Thermal Requirements of Liquid‐Phase Synthesis

Abstract Conventional syntheses of robust Zr‐based metal‐organic frameworks (Zr‐MOFs) rely on harsh solvothermal conditions, precluding the inclusion of fragile functionalities such as enzymes or organisms. Therefore, developing routes to such stable frameworks under ambient conditions remains a significant challenge. Here, we report a mild aqueous solid‐state crystallization (SSC) strategy that enables Zr‐MOF assembly at ambient temperature. This approach transforms an amorphous precursor into a crystalline framework via water‐mediated dynamic ligand exchange. Solid‐state 13 C NMR spectroscopy and density functional theory calculations reveal an acid‐catalyzed associative substitution mechanism at Zr 6 nodes, in which formate modulators are protonated and displaced by fumarate linkers, driving MOF‐801 crystallization without external heating or organic solvent. We further apply this SSC method to other Zr‐MOFs, including functionalized UiO‐66 analogues, establishing it as a general model for ambient MOF assembly. This amorphous‐to‐crystalline transformation represents a new synthetic paradigm for constructing stable porous frameworks under biocompatible conditions and enables the integration of sensitive biomolecules (e.g., enzymes) into robust MOFs. In addition, this method for MOF‐801 formation is universally adaptable for encapsulating various proteins. The enzyme@Zr‐MOF composites significantly enhance enzyme stability in catalytic reactions involving acidic products, demonstrating the necessity of robust Zr‐MOF shells.