Guest-Directed Crystallization of ZIF-8 Regulates Eugenol Binding and pH-Responsive Release

Abstract This study demonstrates guest-directed crystallization of zeolitic imidazolate framework-8 (ZIF-8) on carboxylated cotton, using eugenol as both a fragrance guest and a crystallization modulator to achieve pH-responsive release under mildly acidic, perspiration-like conditions. Particular emphasis is placed on how the timing of eugenol introduction modulates competitive guest–linker interactions during ZIF-8 crystallization, thereby governing guest retention and pH-responsive release. During a 72 h three-step cumulative synthesis, eugenol was introduced either at the onset of ZIF-8 growth or after 48 h to regulate crystal formation, guest-binding state, and subsequent release behavior. Spectroscopic analyses and density functional theory calculations revealed coordination between the phenolic oxygen of eugenol and Zn sites, providing molecular-level evidence for guest-ZIF-8 interactions. Early-stage addition suppressed ZIF-8 nucleation, producing larger crystals and increasing the fraction of framework-coordinated eugenol. Consequently, eugenol release became more strongly pH-responsive because coordinated eugenol was preferentially released upon acid-induced framework degradation. In contrast, introducing eugenol after 48 h led to mostly physical retention within the framework, resulting in diffusion-controlled release with substantially weaker pH dependence. The eugenol-containing ZIF-8 fabrics also exhibited strong antibacterial activity against Escherichia coli through the combined effects of ZIF-8 and eugenol. These findings establish guest-addition timing as an effective synthetic parameter for regulating metal–organic framework crystallization, guest-binding state, and stimulus-responsive release behavior.