Aromatic Zipper Topology Dictates Water‐Responsive Actuation in Phenylalanine‐Based Crystals

Abstract Water‐responsive (WR) materials that reversibly deform in response to relative humidity (RH) changes are gaining increasing interest for their potential in energy harvesting and soft robotics applications. Despite progress, there are significant gaps in the understanding of how supramolecular structure underpins the reconfiguration and performance of WR materials. Here, three crystals are compared based on the amino acid phenylalanine (F) that contain water channels and F packing domains that are either layered (F), continuously connected (phenylalanyl‐phenylalanine, FF), or isolated (histidyl‐tyrosyl‐phenylalanine, HYF). Hydration‐induced reconfiguration is analyzed through changes in hydrogen‐bond interactions and aromatic zipper topology. F crystals show the greatest WR deformation (WR energy density of 19.8 MJ m −3 ) followed by HYF (6.5 MJ m −3 ), while FF exhibits no observable response. The difference in water‐responsiveness strongly correlates to the deformability of aromatic regions, with FF crystals being too stiff to deform, whereas HYF is too soft to efficiently transfer water tension to external loads. These findings reveal aromatic topology design rules for WR crystals and provide insight into general mechanisms of high‐performance WR actuation. Moreover, the best‐performing crystal, F emerges as an efficient WR material for applications at scale and low cost.