This review examines the growing variety of covalent reactions used to achieve the post-assembly modification of self-assembled metallosupramolecular complexes.

Post-assembly modification (PAM) is a powerful tool for the modular functionalization of self-assembled structures. We report a new family of tetrazine-edged Fe^II₄L₆ tetrahedral cages, prepared using different aniline subcomponents, which undergo rapid and efficient PAM by inverse electron-demand Diels–Alder (IEDDA) reactions. Remarkably, the electron-donating or -withdrawing ability of the para-substituent on the aniline moiety influences the IEDDA reactivity of the tetrazine ring 11 bonds away. This effect manifests as a linear free energy relationship, quantified using the Hammett equation, between σ_para and the rate of the IEDDA reaction. The rate of PAM can thus be adjusted by varying the aniline subcomponent.

Fe^II₄L₆ tetrahedral cage 1 undergoes post-assembly modification (PAM) via a Diels-Alder cycloaddition of the anthracene panels of the cage with tetracyanoethylene. The modified cage 2 possesses an enclosed cavity suitable for encapsulation of the fullerene C₆₀ whereas original cage 1 forms a unique covalent adduct through a Diels-Alder cycloaddition of three of its anthracene ligands with C₆₀. This adduct undergoes further PAM via reaction of the remaining three ligands with tetracyanoethylene, enabling the isolation of two distinct products depending on the order of addition of C₆₀ and tetracyanoethylene. The modified cage 2 was also able to bind an anionic guest, [Co(C₂B₉H₁₁)₂]⁻, which was not encapsulated by the original cage, demonstrating the potential of PAM for tuning the binding properties of supramolecular hosts.