Complexation and chiral recognition thermodynamics of γ-cyclodextrin with N-acetyl- and N-carbobenzyloxy-dipeptides possessing two aromatic rings

The stability constants (K) and the standard free energy (DeltaGdegrees), enthalpy (DeltaHdegrees), and entropy changes (AS') for the complexation of gamma-cyclodextrin with 34 enantiomeric and diastereomeric N-acetyl- and N-carbobenzyloxy-D/L-dipeptides with two aromatic moieties were determined in aqueous buffer solution at 298.15 K by titration microcalorimetry. Chiral recognition of the enantiomeric dipeptide pairs by gamma-cyclodextrin was found to be fairly poor, exhibiting only small percentage differences in K, while the diastereomeric dipeptides were discriminated to much greater extent with affinity differences of up to 6-7 times. The complex structures of several selected pairs were elucidated by NMR techniques. Combining the microcalorimetric and NMR data, the complexation and chiral recognition behavior of gamma-cyclodextrin is discussed in particular in terms of the length, bulkiness, and flexibility of the tether connecting the two aromatic moieties in a guest.