A general and green approach of pH‐sensitive ZIF‐67 for encapsulating active substances

Abstract Zeolitic imidazolate framework‐67 (ZIF‐67) has emerged as a promising carrier for active substances (AS) due to its biocompatibility and acid‐triggered degradation behavior. Conventional loading strategies often involve multi‐step post‐synthetic modifications or one‐pot processes employing toxic organic solvents. This study presents a facile one‐pot synthesis method for encapsulating AS into ZIF‐67 in deionized water within 2 h under ambient conditions. This method exhibits broad applicability, enabling effective encapsulation of both hydrophobic and hydrophilic molecules with molecular weights ranging from low to high, with loading efficiencies between 12.17% and 56.11%. While free compounds were released rapidly in a pH‐independent manner, both CA@ZIF‐67 and EGCG@ZIF‐67 proved pH‐responsive sustained release profiles, with their mechanisms best described by the first‐order model and Fickian diffusion, respectively. Moreover, these composites demonstrated synergistic and pH‐dependent antibacterial activity against Escherichia coli and Staphylococcus aureus , showing significantly enhanced efficacy in acidic conditions. Furthermore, the formation process, morphological evolution, and release behavior of AS@ZIF‐67 composites were elucidated through Monte Carlo simulations, modified attachment energy theory, and molecular dynamics simulations. This green one‐pot strategy offers a versatile platform for applications in controlled release, antimicrobial systems, and targeted delivery.