Discrete Actuation of Water‐Responsive Crystalline Metal–Peptide Frameworks

Abstract Engineering guest‐responsive materials capable of controlled and precise sorption behavior and structural deformation in response to external stimuli is imperative for various applications. However, existing systems often exhibit complex, unpredictable dynamics, posing challenges for efficient control and utilization. Here, we design crystalline metal–peptide frameworks with tunable water‐responsive (WR) dynamics by assembling glycine‐threonine (Gly‐Thr, GT) or glycine‐serine (Gly‐Ser, GS) peptides with zinc (Zn) ions, achieving either continuous or discrete threshold water‐sorption‐dependent phase transitions. As ambient relative humidity (RH) changes, the Zn‐GT crystal continuously adsorbs or desorbs water, resulting in gradual structural adaptations, similar to those observed in other supramolecular systems. In contrast, the Zn‐GS crystal undergoes stepwise water sorption and structural transitions at specific RH thresholds. These contrasting WR modes arise from differences in water binding and structural dynamics; in Zn‐GT, each coordinating water molecule contributes varying degrees of framework integrity and evaporates sequentially, whereas in Zn‐GS, water molecules with comparable interactions within a flexible framework are released simultaneously during dehydration. Our study demonstrates the mechanism by which host–guest interactions can be harnessed to control dynamic sorption and actuation behavior of supramolecular materials at the molecular level, offering mechanistic insights that may guide the rational design of next‐generation programmable, stimulus‐responsive systems.