Dual-Cavity Basket Promotes Encapsulation in Water in an Allosteric Fashion

We
prepared dual-cavity basket 1 to carry six (S)-alanine residues at the entrance of its two juxtaposed
cavities (289 Å3). With the assistance of 1H NMR spectroscopy and calorimetry, we found that 1 could
trap a single molecule of 4 (K1 = 1.45 ± 0.40 × 104 M–1,
ITC), akin in size (241 Å3) and polar characteristics
to nerve agent VX (289 Å3). The results of density
functional theory calculations (DFT, M06-2X/6-31G*) and experiments
(1H NMR spectroscopy) suggest that the negative homotropic
allosterism arises from the guest forming C–H···π
contacts with all three of the aromatic walls of the occupied basket’s
cavity. In response, the other cavity increases its size and turns
rigid to prevent the formation of the ternary complex. A smaller guest 6 (180 Å3), akin in size and polar characteristics
to soman (186 Å3), was also found to bind to dual-cavity 1, although giving both binary [1⊂6] and ternary [1⊂62] complexes (K1 = 7910 M–1 and K2 = 2374 M–1, 1H NMR spectroscopy). In this case, the computational and experimental
(1H NMR spectroscopy) results suggest that only two aromatic
walls of the occupied basket’s cavity form C–H···π
contacts with the guest to render the singly occupied host flexible
enough to undergo additional structural changes necessary for receiving
another guest molecule. The structural adaptivity of dual-cavity baskets
of type 1 is unique and important for designing multivalent
hosts capable of effectively sequestering targeted guests in an allosteric
manner to give stable supramolecular polymers.