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. PdnL2n cages are amongst 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 non-planarity, 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.