Chiral Recognition Thermodynamics of β-Cyclodextrin: The Thermodynamic Origin of Enantioselectivity and the Enthalpy−Entropy Compensation Effect

Abstract

The complex stability constant (K), standard free energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) for the 1:1 inclusion complexation of 43 enantiomeric pairs of chiral guests with β-cyclodextrin at 25 °C have been determined by microcalorimetry. The overall complexation thermodynamics are related to variations in the structure of the cyclic and acyclic guest, including its aromatic or aliphatic nature, the chain length, branching, flexibility, charge, and incorporated oxygen atom. The differences in the thermodynamic parameters due to the chirality are comprehensively discussed in terms of the stereochemistry, skeleton, chain length, and functional groups of the guest, and the mode of penetration upon inclusion complexation. The enthalpy−entropy compensation plot, using the differential thermodynamic parameters (ΔΔH° and ΔTΔS° at 298.15 K) for the chiral recognition equilibrium, gave an excellent straight line of unit slope, from which the isokinetic, or isoenantiodifferentiating, temperature was calculat...