Interactions of α-, β- and γ-cyclodextrin with bicyclo[2.2.2]octane-1,4-derivatives in aqueous solution and in the gas phase A microcalorimetric and molecular modelling study

Abstract

Binding of 1,4-di-R-bicyclo[2.2.2]octanes [R = OH (bic), Me (bim)] to α-, β- and γ-cyclodextrin (α-CD, β-CD and γ-CD) in the gas phase and in aqueous solution have been studied by force-field computations and by isothermal titration microcalorimetry, respectively. For bic, a 1:1 stoichiometric model was assumed in the treatment of the microcalorimetric data. In the gas phase, for both α-CD and β-CD, bim penetrates less deeply into the cavity than bic. The shallow penetration of bim allows a second α- cyclodextrin molecule to bind, in agreement with the 1:2 complex observed in a solvent mixture by NMR measurements, as reported earlier. In aqueous solution, β-CD binds to bic with moderate Gibbs energy change, a large and negative heat capacity change and compensating temperature dependences for the enthalpy and the entropy changes. α-CD and γ-CD bind weakly to bic in solution, whilst large binding energies were obtained for both guests for the gas-phase interactions with α-CD and β-CD.