Molecular Encapsulation in Pyrogallolarene Hexamers Under Nonequilibrium Conditions

Abstract

Pyrogallol[4]arene is a macrocycle with a concave surface and 12 peripheral hydroxyl groups that mediate its self-assembly to form hexamers of octahedral symmetry in the solid state, in solution, and in the gas phase. These hexamers enclose approximately 1300 Å(3) of space, which is filled with small molecules. In this study, we show that solvent-free conditions for guest entrapment in these hexamers, using molten guest molecules as solvent and allowing the capsules to assemble during cooling, results in exceptionally kinetically stable encapsulation complexes that are not formed in the presence of solvent and are not thermodynamically stable. The capsules' kinetic stabilities are strongly dependent on the size and shape of both guest and solvent molecules, with larger or nonplanar molecules with rigid geometries providing enhanced stability. The greatest observed barrier to guest exchange, ΔG(‡) = 32 ± 0.7 kcal mol(-1) for encapsulated CCl(4) → encapsulated pyrene, is, to the best of our knowledge, indicative of the most powerful kinetic trap ever observed for a synthetic, hydrogen-bonded encapsulation complex. Detailed NMR studies of the structures of the assemblies and the kinetics and mechanisms for guest exchange reveal that subtle differences in guest and solvent structure can impart profound effects on the behavior of the systems. Kinetic and thermodynamic stability, capsule symmetry and structure, guest tumbling rates, susceptibility to disruption by polar solvents, and even the mechanism for equilibration-the presence or absence of supramolecular intermediates-are all greatly influenced. The strongest observed kinetic traps provide encapsulation complexes that are not at equilibrium but are nonetheless indefinitely persistent at ambient temperatures, a property that invites future applications of supramolecular chemistry in open systems where equilibrium is not possible.

Anion-capped metallohost allows extremely slow guest uptake and on-demand acceleration of guest exchange

“…As to generating a kinetically trapped state as the first step (Fig. 1b(i)), there have been several host molecules that temporarily bind a kinetically favoured guest prior to the binding with a thermodynamically favoured guest31323334353637383940414243. Therefore, we envisioned a kinetically trapped host–guest system having the second step in which removal of the kinetic barrier can initiate the guest uptake or exchange (Fig.…”

A chiral member of the family of organic hexameric cages

“…This is in sharp contrast with capsules 4 and 5 that do not have portals and, therefore, they have to dissociate (partially or fully) for guest uptake. Indeed, it has been shown that guest uptake for 4 is hedged by a high kinetic barrier, [35][36][37] while it is completely blocked for coordination-based capsule 5. For capsule 6 entrance portals are inevitably present, however, the capsule is much more conformationally labile and complexation studies have not been reported.…”

On the mechanism of mechanochemical molecular encapsulation in peptidic capsules

“…21 An exception in this regard is a tightly sealed pyrogallolarene hexameric capsule that is surprisingly kinetically stable in non-polar solvents and encapsulation can be achieved by neat-melting with guests. [22][23][24] We recently reported a hydrogen bonded peptidic capsule that is kinetically stable in non-polar solvents ( Fig. 1 and 2).…”