H‐Bond Modulation Mechanism for Moisture‐driven Bacteriostat Evolved from Phytochemical Formulation

Abstract The development of environment‐friendly bacteriostats in humid atmosphere is designated as a crucial step pointing to sustainable antibiotic‐free alterative. Thanks to the excellent biosafety and intrinsic bacteriostatic attributes, bioactive phytochemical formulations become a fascinating substitute for traditional antibiotics; yet, it remains a challenge to deliver them toward moisture‐activated bacteriostatic application due to the unclear release mechanism and bacteriostatic behavior. Benefitting from “green” metal–organic frameworks (MOFs) evolved from natural γ‐cyclodextrin (γ‐CD) and potassium ion (K⁺), an intelligent moisture‐activated phytochemical formulation is developed, which is featured by grafting bacteriostatic vanillin (a specific phytochemical extracted from Rutaceae vanilla bean) into microporous structure of MOFs via ligand implantation mechanism. According to the molecular simulation docking, the dominant pattern of host–guest structure is characteristic for H‐bond with a length of 1.9 Å, beneficial for the sterling adsorption capacity. Nevertheless, under moisture exposure, the intermolecular H‐bond is disrupted for vanillin release to destroy bacterial membrane structure, accelerate protein decomposition, and especially inhibit virulence gene transcription of cfa gene in Escherichia coli and sea gene in Staphylococcus aureus, directing to upgrade the insights into the bacteriostatic potency of phytochemicals in high‐humidity circumstance.