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

Binding of 1,4-di-R-bicyclo[2.2.2]octanes [R = OH (bic), Me (bim)] to alpha-, beta- and gamma-cyclodextrin (alpha-CD, beta-CD and gamma-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 alpha-CD and beta-CD, bim penetrates less deeply into the cavity than bic. The shallow penetration of bim allows a second alpha-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, beta-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. alpha-CD and gamma-CD bind weakly to bic in solution, whilst large binding energies were obtained for both guests for the gas-phase interactions with alpha-CD and beta-CD.