Electronic tuning of dynamic imine bonds enables programmable pore gating in metal–organic frameworks

Metal–organic frameworks (MOFs) are promising host matrices for molecular encapsulation, yet their application is often limited by fixed pore apertures that exclude guest molecules larger than the pore openings. Herein, we overcome this limitation by electronic tuning of dynamic imine bonds to induce reversible pore gating that transiently expands framework accessibility beyond its intrinsic aperture. By incorporating imine-based linkers bearing electron-donating/withdrawing substituents into a robust Zr-based MOF scaffold via postsynthetic linker exchange, we systematically modulate imine dissociation equilibria while preserving crystallinity. A linear correlation between Hammett substituent constants and imine bond stability establishes electronic effects as a predictive handle for programming framework dynamics. Systematic variation of substituents establishes an optimal metastable regime in which reversible linker dissociation permits size-adaptive guest uptake without structural degradation. As a proof of concept, paclitaxel and other therapeutics are efficiently encapsulated, and the resulting materials exhibit good biocompatibility together with programmable, environment-responsive release kinetics under physiological conditions. Guided by electronic effects, this study programs the dynamics of reversible imine bonds in metal-organic frameworks, enabling adaptive pore opening for efficient drug loading and controlled release.