Efficient Loading and Kinetic Trapping of Hexameric Pyrogallolarene Capsules in Solution

Abstract

Solvent matters: By carrying out the assembly of pyrogallolarene hexamers under thermal conditions in the absence of solvent, highly efficient loading of guest molecules to produce kinetically trapped assemblies was achieved. Such products are not formed when the solvents are present (see schematic).

Mechanically induced pyrogallol[4]arene hexamer assembly in the solid state extends the scope of molecular encapsulation

“…Past work in our lab and by others has shown that pyrogallol[4]arene hexamers are competent to encapsulate alkanes, alkenes, arenes, amines, and carboxylic acids that have suitable size and shape to fill the capsules' interiors, sometimes aided by the co-encapsulation of solvent molecules. 12 , 17 , 26 – 31 The encapsulation of amines and carboxylic acids is observed at equilibrium in solution, whereas solvent occupancy of the capsules is typical for alkanes, alkenes, and arenes at the mM concentrations used for most solution phase studies. 26 – 28 , 30 These guests can be loaded efficiently into the capsules using the melting and cooling cycle described above, followed by dissolution in aprotic solvents for solution studies under nonequilibrium conditions.…”

“…Our lab has previously shown that hexamers of 1a are the most kinetically stable known self-assembling molecular capsules governed by hydrogen bonding, with observed Δ G ‡guest exchange > 30 kcal mol –1 for the best guests in some nonpolar solvents. 26 – 28 With this high kinetic stability, encapsulation complexes can be formed by cooling molten mixtures of host and guest in the absence of solvent, and subsequently dissolving the assembled capsules. 26 The resulting encapsulation complexes are thermodynamically unstable but kinetically trapped.…”

“… 26 – 28 With this high kinetic stability, encapsulation complexes can be formed by cooling molten mixtures of host and guest in the absence of solvent, and subsequently dissolving the assembled capsules. 26 The resulting encapsulation complexes are thermodynamically unstable but kinetically trapped. 27 Heating is required to reach equilibrium, at which solvent occupancy of the capsules is preferred.…”

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).…”