Product‐Triggered Adaptive Evolution From a Pd 4 L 2 to a Pd 6 L 3 Conjoined Cage via Catalytic Dehydration of p ‑Quinone Methide Precursors

ABSTRACT Supramolecular chemistry aims to emulate the dynamic structural adaptations and induced‐fit conformational changes of enzymes that are fundamental to their biological function. In this work, we synthesized an adaptive Pd 4 L 2 coordination cage using the newly developed pyridinium‐based ligand L with cis ‐capped Pd (II) salt. Upon guest encapsulation, conformational adjustment provides direct structural evidence for the adaptive nature of cage 1 by X‐ray crystallographic study. Within the hydrophobic pocket of the capsule, 4‐(1‐hydroxy‐1‐phenylethyl) phenol ( S1 ), a known para ‐quinone methide ( p ‐QM) precursor, undergoes spontaneous dehydration to the alkene product P1 in water. Kinetic studies and control experiments reveal that the cage 1 plays a vital role in significantly accelerating the dehydration process, affording the alkene product with markedly enhanced efficiency compared to the background reaction. Then generated alkene products act as a chemical stimulus driving the transformation of Pd 4 L 2 to a Pd 6 L 3 conjoined cage through an induced‐fit mechanism, as unambiguously confirmed by SCXRD. This work offers fresh insights into enzyme‐like adaptive behavior and unveils responsive supramolecular catalysis.