Distinctive Pressure Effects on the Association Equilibrium in Cyclodextrin Group-Inclusion Complex as Studied with Electron Paramagnetic Resonance

Abstract

The cyclic oligosaccharide cyclodextrin (CD) has been shown to form isomeric guest−host complexes in which each functional group in the guest molecule is individually included by the cyclodextrin cavity. Spectroscopic separation of these isomer complexes or group-in complexes has been demonstrated only when free radical probes were used as guest molecules, followed by the detection with electron paramagnetic resonance (EPR) spectroscopy. In the present study, using a high-pressure EPR system, external static pressure up to 700 bar (70 MPa) was applied to the sample solution in a pressure-proof EPR sample tube, and the changes in the equilibrium constants of group-in complexes were monitored. The external pressure either increased or decreased the equilibrium constant, depending on the sizes of the included group relative to that of the cyclodextrin cavity. For instance, when the free radical probe α-phenyl-2,4,6-trimethoxybenzyl tert-butyl nitroxide ((CH3O)3Ph-CH(Ph)-N(O·)-t-Bu) was mixed with γ-CD, both phenyl-in and tert-butyl-in complexes were identified. With an increasing external pressure, the equilibrium between tert-butyl-in and phenyl-in complexes shifted to the phenyl-in complex side. In contrast, when β-CD was used the equilibrium shifted to the tert-butyl-in complex side. The analysis of the pressure effect in various group-in complexes with γ-CD or β-CD has revealed that there is a pressure-dependent competing complexation between the included group and water molecules.