Structural Transformations of Metal–Organic Cages through Tetrazine-Alkene Reactivity

The assembly of metal-organic cages is governed by metal ion coordination preferences and the geometries of the typically rigid and planar precursor ligands. Pd<i>_n</i>L_2<i>n</i> cages are among the most structurally diverse, with subtle differences in the metal-ligand coordination vectors resulting in drastically different assemblies, however almost all rely on rigid aromatic linkers to avoid the formation of intractable mixtures. Here we exploit the inverse electron-demand Diels-Alder (IEDDA) reaction between tetrazine linker groups and alkene reagents to trigger structural changes induced by post-assembly modification. The structure of the 1,4-dihydropyridazine produced by IEDDA (often an afterthought in click chemistry) is crucial; its two sp³ centers increase flexibility and nonplanarity, drastically changing the range of accessible coordination vectors. This triggers an initial Pd₄L₈ tetrahedral cage to transform into different Pd₂L₄ lantern cages, with both the transformation extent (thermodynamics) and rate (kinetics) dependent on the alkene dienophile selected. With cyclopentene, the unsymmetrical 1,4-dihydropyridazine ligands undergo integrative sorting in the solid state, with both head-to-tail orientation and enantiomer selection, leading to a single isomer from the 39 possible. This preference is rationalized through entropy, symmetry, and hydrogen bonding. Subsequent oxidation of the 1,4-dihydropyridazine to the aromatic pyridazine rigidifies the ligands, restoring planarity. The oxidized ligands no longer fit in the lantern structure, inducing further structural transformations into Pd₄L₈ tetrahedra and Pd₃L₆ double-walled triangles. The concept of controllable addition of limited additional flexibility and then its removal through well-defined reactivity we envisage being of great interest for structural transformations of any class of supramolecular architecture.