(517h) Molecular Recognition of Simple Hydrophobic Guests by Cavitand Hosts In Aqueous Solution

Cavitands are concave, bowl-shaped molecules, which mimic bio-receptors and bind nonpolar guests of complementary size and shape in the aqueous solution. The ability to form stable capsules lends potential application of cavitands as delivery vehicles that shield hydrophobic drugs within their confines. Using molecular simulations we are investigating the solvent-mediated interactions between cavitands with hydrophobic guest inclusions and the encapsulation of guests in dimeric cavitand assemblies. Two sets of simulations have been performed to characterize the interactions between deep-cavity cavitands with simple Lennard-Jones type guests and a more realistic adamantane guest, which is experimentally known to bind strongly to the deep-cavitand. Interactions between two cavitand hosts in presence of different hydrophobic guests are also evaluated to understand the process of formation of capsular assemblies. The interactions between the hosts and guests are evaluated using potential-of-mean-force (PMF) calculations, which are deconvoluted into their direct host-guest and indirect solvent-mediated contributions. Our results indicate strong binding interaction between the hosts and guests and also explain the role of solvent in the recognition process.