Molecular recognition of pseudo-peptides in β-cyclodextrin

The phenomenon of molecular recognition is important in all biological reactions and also in the design of materials with new properties. Studies of amino acid and peptide substrates in various host receptors contribute to an understanding of intermolecular interactions relevant to recognition. CD complexes associate via weak non-covalent interactions, which makes the useful model systems for studies of molecular recognition. In this thesis, solid-state structural studies of β-Cyclodextrin (β-CD) complexes with different N-acetylated pseudo-peptides are reported. Resulting analyses of the crystal structures show that β-CD has value as a host receptor for the study of molecular recognition of small biologically relevant molecules. The ‘intermediate’ type dimeric CD lattice provides a scaffold with regions analogous to a macromolecular binding pocket, ideal for examining changes in intermolecular interactions associated with different guests. The effects of two different perturbations of the system have been systematically examined. Studies of three different β-CD complexes with N-acetylated- L-phenylalanine derivatives, where changes in either carboxyl-backbone or side chain functional groups have been incorporated, are compared. Hydrophilic hydrogen bonding interactions and aromatic or van der Waals interactions that take place within the hydrophobic torus of the CD dimer are contrasted. The importance of kinetic energy with respect to molecular recognition in these systems is also discussed, based on temperature dependent crystal structures of the 2:2 N-acetyl-L-phenylalanine methyl ester complex with β-CD. Several different disordered guest molecules with different intermolecular interactions are observed. With future studies, a database of energetically similar nonbonding interaction schemes can be assembled, which would prove useful for those interested in molecular modeling of recognition