Chiral host–guest complexes: interaction of α-cyclodextrin with optically active benzene derivatives

Abstract

The binding to α-cyclodextrin of a series of small, chiral benzene derivatives has been studied by direct reaction microcalorimetry and by a spectral competitive inhibition technique. A small, but distinct, chiral discrimination is demonstrated in the binding of the optical isomers of phenylalanine and α-methylbenzylamine, whereas mandelic acid, amphetamine, and phenyltrifluoroethanol show no such effect. The enthalpies of complex formation are remarkably similar for all compounds studied, ΔH ca.–3.5 kcal mol^–1(25 °C; pH 11.0; 0.1M-phosphate buffer). No obvious correlation of chiral effects with molecular structure has been found. It is concluded that insertion of the aromatic ring in the central cavity of α-cyclodextrin provides the major driving force for complex formation, and that chiral interactions external to the cavity are of minimal importance in this class of compounds.