Host-Guest Interactions in Enzyme@MOF Biocomposites: Principles and Design

Metal-organic frameworks (MOFs), owing to their exceptional porosity and tunable chemical functionality, have emerged as leading platforms for enzyme immobilization. The nature and magnitude of interfacial interactions between enzymes and MOF carriers fundamentally govern the conformational integrity, substrate accessibility, and catalytic stability of the resulting biocomposites. This review systematically examines five principal categories of driving forces underlying these interactions: hydrophobic and hydrophilic interactions that modulate carrier polarity to induce lipase lid-opening activation or preserve native enzyme hydration; electrostatic interactions exploited through charge-complementarity loading and surface engineering; hydrogen bonding that directs the ordered assembly of crystalline biohybrid frameworks while actively regulating enzyme conformation; coordination interactions between unsaturated metal nodes and enzyme residues that enable site-specific anchoring, requiring careful balance between binding strength and catalytic flexibility; and covalent bonding strategies including Schiff base reactions, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling, and glutaraldehyde cross-linking that ensure robust immobilization and superior recyclability. Furthermore, the synergistic interplay among these multiple intermolecular forces is highlighted as a defining feature of high-performance nanobiocatalytic systems. A comprehensive understanding of the enzyme-MOF interfacial microenvironment is expected to provide mechanistic insight and practical guidance for the rational design of next-generation immobilized enzyme systems in biocatalysis, biosensing, and sustainable synthesis.