Raymond and coworkers developed a supramolecular host ML (4 gallium ions and 6 ligands for each complex) that self-assembles via metal-ligand interaction in aqueous solution. This container molecule is polyanionic and thus its tetrahedron-shaped cavity is capable of encapsulating and stabilizing a cationic molecule. Consequently, encapsulated molecule can be easily protonated as a resulting carbocation from protonation is stabilized by the surrounding anions. Raymond utilized this property to perform acid-catalyzed Nazarov cyclization. The catalyst accelerates the reaction by over one million fold, making it the most efficient supramolecular catalyst to date. It was proposed that such a high catalytic activity does not arise just from the increased basicity of the encapsulated substrate but also from the constrictive binding that stabilize the transition state of the cyclization. Unfortunately, this catalyst has a problem with product inhibition. To by pass that problem, the product of the cyclization reaction could be reacted with a dienophile transforming it into a Diels-Alder adduct that no longer fits inside the catalyst cavity.
In this case, the supramolecular host was initially designed to simply capture cationic guests. Almost a decade later, it was exploited as a catalyst for Nazarov cyclization.