Product-Triggered Adaptive Evolution From a Pd4L2 to a Pd6L3 Conjoined Cage via Catalytic Dehydration of p‑Quinone Methide Precursors.

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 Pd4L2 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 Pd4L2 to a Pd6L3 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.