Supramolecular Control of Fullerene Recognition and Reactivity through Nanocapsule Confinement

ConspectusFullerenes have a wide range of applications across biomedicine, electronics, and nanotechnology, yet their broader application depends on the ability to control their molecular recognition and chemical reactivity. Supramolecular host-guest chemistry offers powerful opportunities in this context by enabling selective encapsulation and modulation of reactivity within confined environments. Since their discovery, substantial efforts have been devoted to developing efficient purification protocols to obtain high-purity fullerenes (particularly higher fullerenes C_n, <i>n</i> > 70) from fullerene soot, thereby avoiding tedious and costly chromatographic separations. The use of molecular receptors for fullerene purification via host-guest interactions affords good selectivity, requires no specialized equipment, and enables recyclable systems through careful host design. To date, most supramolecular receptors have demonstrated differential recognition of fullerenes through distinct binding affinities, while translation of such selectivity into practical purification and, more importantly, into predictable control over reactivity remains a central challenge. Indeed, to further advance fullerene chemistry, access to isomer-pure polyfunctionalized fullerenes is essential. However, conventional functionalization methods typically yield mixtures of multiple adducts with poor regioselectivity, and chromatographic purification alone is often insufficient. An alternative strategy involves confining fullerenes within host cages that act as supramolecular masks, selectively shielding part of the fullerene surface, which has emerged as an effective approach for the direct synthesis of isomer-pure polyadducts.This Account describes our development of tetragonal prismatic nanocapsules as a unified platform for the control of fullerene recognition and reactivity. Through careful host design and detailed investigation of binding sites and binding modes, these nanocapsules enable the selective encapsulation of fullerenes with different shapes and sizes (C₆₀, C₇₀, C₈₄, and fullertubes) while also providing a confined environment that governs subsequent chemical transformations, such as the regioselective functionalization of C₆₀ and C₇₀.In this context, supramolecular confinement not only enables selective fullerene binding but also modifies the guest's accessible surface area, thereby enabling regioselective functionalization via a supramolecular mask strategy and introducing a new level of selectivity. By systematically correlating nanocapsule structure with binding behavior and reaction outcomes, we demonstrate how cavity size matching, window accessibility, and postbinding host-guest interactions can be leveraged to achieve selective encapsulation and predictable regioselectivity in fullerene functionalization. These studies show the potential of the supramolecular control over selectivity and reactivity in highly symmetric guests.The principal remaining challenges include achieving high selectivity for specific substrates and effective discrimination among multiple competing guests through distinct, well-defined binding modes, as well as extending confinement-controlled reactivity to increasingly complex substrates. These challenges will be addressed by developing novel supramolecular containers capable of predictable recognition, enhanced selectivity, and precise control of reactivity within confined environments.