On the multivalency of large-ring cyclodextrins.

The inclusion complexes of several large-ring cyclodextrins with a number of monovalent ligands (five or six adamantane molecules; CDn/mADA; n = 11, 12, 13, 14, 21, 26; m = 5 (for n = 11 to 14) or 6 (for n = 21, 26)) were examined with molecular dynamics simulations. The results demonstrate the high affinity of the LR-CDs to accommodate in their cavities this hydrophobic test particle. Most of the simulation time two guest molecules associate with the CD11 macrocycle. Two to four guest molecules are included in the cavities of CD12, CD13 and CD14 for the total of about 50% to 75% of the simulation time. Higher order associates of CD21 and CD26 with three to five adamantane substrates, comprise more than 40.0% of the snapshots taken from the simulation trajectories, and they still have remaining unoccupied binding sites that could accommodate even more adamantane molecules. Cluster analyses were performed with the k-mean and the bottom up agglomerative hierarchical methods. These LR-CDs, with theirs more than one docking sites are suitable candidates as multivalent receptors for specifically designed multivalent ligands.