Mechanochemistry, a sustainable and efficient approach, is now used to encapsulate biocatalysts like enzymes within MOFs (enzyme@MOFs). Yet, achieving ultrafast, eco-friendly, and high-yield synthesis of enzyme@MOFs, with potential for mitigating biocatalyst and industrial MOF production improvement, remains challenging. In this study, we illustrated the enzyme one-pot mechanical encapsulation within zeolitic imidazolate framework-90 (ZIF-90), a MOF subfamily. A substantial yield (ca. 80%) was achieved in only 10 s at 8 Hz or lower frequencies, assisted by a small amount (∼100 μl) of Tris buffer solution. The encapsulated enzyme catalase (CAT), responsible for decomposing hydrogen peroxide, maintains its bioactivity after mechanical treatment. Additionally, the enzyme gains protection from digestion (e.g., proteinase K) due to the size-sheltering effect. Simulations of energy transfer and experimental findings reveal that a buffer solution containing primary amines affects linker deprotonation, thereby facilitating the rapid formation of a well-defined 3D structure of enzyme@ZIF-90 crystals during ultrafast milling reactions. We further demonstrated our mechanical approach by encapsulating bovine serum albumin and Escherichia coli in ZIF-90, highlighting the versatility of this method for crafting MOF biocomposites across diverse industrial applications.

The capability of materials to interconvert between different phases provides more possibilities for controlling materials’ properties without additional chemical modification. The study of state-changing microporous materials just emerged and mainly involves the liquefication or amorphization of solid adsorbents into liquid or glass phases by adding non-porous components or sacrificing their porosity. The material featuring reversible phases with maintained porosity is, however, still challenging. Here, we synthesize metal-organic polyhedra (MOPs) that interconvert between the liquid-glass-crystal phases. The modular synthetic approach is applied to integrate the core MOP cavity that provides permanent microporosity with tethered polymers that dictate the phase transition. We showcase the processability of this material by fabricating a gas separation membrane featuring tunable permeability and selectivity by switching the state. Compared to most conventional porous membranes, the liquid MOP membrane particularly shows the selectivity for CO₂ over H₂ with enhanced permeability.

The function of an enzyme depends on its dynamic structure, and the catalytic mechanism has long been an active focus of research. The principle for interpreting protein selectivity and fidelity stems from optimization of the active site upon protein–substrate complexation, i.e., a lock-and-key configuration, on which most protein–substrate molecule binding recognition, and hence drug discovery, relies. Yet another thought has been to incorporate the protein folding interior tunnels for stereo- and regio-selectivity along the protein–substrate or protein–ligand/inhibitor binding process. Free energy calculations provide valuable information for molecular recognition and protein–ligand binding dynamics and kinetics. In this study, we focused on the kinetics of cytochrome P450 proteins (CYP450s) and the protein interior tunnel structure–dynamics relationship in terms of the substrate binding and leaving mechanism. A case in point is given by the prostaglandin H₂ (PGH₂) homologous isomerase of prostacyclin synthase. To calculate the reactant and product traversing the tunnels to and from the heme site, the free energy paths and tunnel potentials of mean force are constructed from steered molecular dynamics simulations and adaptive basing force umbrella sampling simulations. We explore the binding tunnels and critical residue lining characteristics for the ligand traverse and the underlying mechanism of CYP450 activity. Our theoretical analysis provides insights into the decisive role of the substrate tunnel binding process of the CYP450 mechanism and may be useful in drug design and protein engineering contexts.