Molecular recognition in cyclodextrin complexes of amino acid derivatives. 2. A new perturbation: the room-temperature crystallographic structure determination for the N-acetyl-p-methoxy-L-phenylalanine methyl ester/beta-cyclodextrin complex.
Cyclodextrins (CDs) are cyclic oligosaccharides that encapsulate various small organic molecules, forming inclusion complexes. Because CD complexes are held together purely by noncovalent interactions, they function as excellent models for the study of chiral and molecular recognition mechanisms. Recently, room-temperature crystallographic studies of both the 2:2 N-acetyl-L-phenylalanine methyl ester/beta-CD and 2:2 N-acetyl-L-phenylalanine amide/beta-CD complexes were reported. The effect of changes in carboxyl backbone functional group on molecular recognition by the host CD molecule was examined for the nearly isomorphous supramolecular complexes. A new perturbation of the system is now examined, specifically perturbation of the aromatic side chain. We report a room-temperature crystal structure determination for the 2:2 N-acetyl-p-methoxy-L-phenylalanine methyl ester/beta-CD inclusion complex. The complex crystallizes isomorphously with the two previously reported examples in space group P1; the asymmetric unit consists of a hydrated head-to-head host dimer with two included guest molecules. The crystal packing provides both a nonconstraining extended hydrophobic pocket and an adjacent hydrophilic region, where hydrogen-bonding interactions can potentially occur with primary hydroxyl groups of neighboring CD molecules and waters of hydration. The rigid host molecules show no sign of conformational disorder, and water of hydration molecules exhibit the same type of disorder observed for the other two complexes, with a few significant differences in locations of water molecules in the hydrophilic region near guest molecules. There is evidence for modest disorder in the guest region of an electron density map. In comparing this system with the two previously reported complexes of phenylalanine derivatives, it is found that the packing of the guest molecules inside the torus of the CD changes upon substitution of a methoxy group at the para position of the aromatic phenyl ring. Backbone hydrogen-bonding interactions for the guest molecules with the CD primary hydroxyls and waters also change. This structure determination is a new and revealing addition to a small but growing database of amino acid and peptidomimetic interactions with carbohydrates.
Clark
J L
JL
Department of Chemistry, University of Nebraska-Lincoln, 68588-0304, USA.
Booth
B R
BR
Stezowski
J J
JJ
D018360:Crystallography, X-Ray; D003505:Cyclodextrins / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; C439088:N-acetyl-p-methoxy-L-phenylalanine methyl ester-beta-cyclodextrin complex; D047392:beta-Cyclodextrins; D010649:Phenylalanine