The Structure of the Cyclodextrin Complex. XIX. Crystal Structures of Hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin Complexes with (S)- and (R)-Mandelic Acid. Chiral Recognition through the Induced-Fit Conformational Change of the Macrocyclic Ring

Abstract

Abstract Hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin (methyl-α-CDx) forms crystalline inclusion complexes with (S)-mandelic acid (S-MA) and (R)-mandelic acid (R-MA). Both crystals are monoclinic, and the space group is P21 with cell dimensions: a=13.123(2), b=23.187(4), c=13.113(2) Å, β=107.19(1)° for the S-MA complex, a=11.624(2), b=23.739(4), c=13.786(2) Å, β=106.56(1)° for the R-MA complex. The structures were solved by inspection of a Patterson map and the R-map method, and refined by the block-diagonal least-squares method to the R-values of 0.087 for the S-MA complex and 0.055 for the R-MA complex. In the S-MA complex, the methyl-α-CDx molecule, which has a pseudo two-fold symmetry, loosely includes the phenyl group of S-MA. The hydroxyl and carboxyl groups of S-MA protrude from the O(2), O(3) side of the methyl-α-CDx cavity and form hydrogen bonds with water molecules located outside the host cavity. The methyl-α-CDx molecule in the R-MA complex tightly binds the R-MA molecule which is deeply inserted into the host cavity. The hydroxyl group of R-MA is hydrogen-bonded to an O(2) oxygen atom of host methyl-α-CDx. The comparison of the two structures suggests that the complex formation induces the conformational change of the host molecule to accommodate S-MA or R-MA more suitably within the cavity.