Conformational Adaptivity and Isomerization Pathway Enable Multi‐Stimuli‐Responsive Assembly and Interconversion of Water‐Soluble Metal–Organic Cages

Multi‐stimuli‐responsive assembly of water‐soluble, high‐nuclearity metal–organic cages (MOCs) offers attractive opportunities for adaptive supramolecular systems, but balancing structural definition with flexibility remains a central challenge. Here, we report that an adaptive ligand ( L2 ) enables access to a series of M 3n L 2n cages within a single coordination framework, including octahedral, tubular, and bowl‐shaped Pd 6 ( L2 ) 4 cages, as well as a Pd 12 ( L2 ) 8 icosahedron. These architectures reversibly interconvert in response to changes in temperature, concentration, solvent environment, and guest binding. In contrast, a rigid analogue ( L1 ) yields a single Pd 6 ( L1 ) 4 octahedral cage. Mechanistic studies, combined with single‐crystal X‐ray diffraction analysis, reveal that interconversion between cages of different nuclearities proceeds primarily via cage isomerization within intact frameworks rather than through classical stepwise growth, providing a kinetically efficient route to higher‐order structural complexity and organization. These results establish the integration of conformational adaptivity with cage isomerization pathways as a general design principle for multi‐stimuli‐responsive supramolecular systems in water.