Molecular Recognition in Cyclodextrin Complexes of Amino Acid Derivatives:  The Effects of Kinetic Energy on the Molecular Recognition of a Pseudopeptide in a Nonconstraining Host Environment as Revealed by a Temperature-Dependent Crystallographic Study

The crystal structure of a triclinic 2:2 inclusion complex of β-cyclodextrin with N-acetyl-l-phenylalanine methyl ester has been determined at several temperatures between 298 and 20 K to further study molecular recognition using solid-state supramolecular β-cyclodextrin complexes. The study reveals kinetic energy dependent changes in guest molecule conformations, orientations, and positions in the binding pocket presented by the crystal lattice. Accompanying these changes are observable differences in guest−guest interactions and hydrogen-bonding interactions in the binding pocket that involve guest molecules, water of hydration molecules, and β-cyclodextrin molecules. On the basis of the differences observed in the crystal structures, we present a solid-state example of a system that displays the properties of both classical and quantum chemical models. At higher temperatures, the structure conforms to a classical mechanical model with dynamic disorder. At lower temperatures, the observations conform to examples in which there is static disorder representative of models in which quantum states differing in conformation, position, and orientation of components in the crystal structure are occupied. Ab initio theoretical calculations on the different guest molecule conformations have been carried out. Superpositions of theoretical electrostatic surface potential diagrams on the observed molecular positions in the complexes provide confidence that the deconvolution of the guest molecule disorder is acceptable. Temperature-dependent solid-state magic angle spinning deuteron NMR measurements provide evidence for large-amplitude, diffusive motion on a microsecond time scale in the complex.