Inclusion complexes of purine nucleosides with cyclodextrins: II. Investigation of inclusion complex geometry and cavity microenvironment

Abstract

Inclusion complex formation between purine nucleosides and cycloamyloses (cyclodextrins) has been examined by solubility, circular dichroism, ultraviolet spectrophotometry, and NMR techniques to explore structure-binding relationships, inclusion complex geometry, and the cavity microenvironment. Formation constants of the inclusion complexes were determined by monitoring changes in solubility or circular dichroism spectra with added cyclodextrin. By using various blocking functional groups at different sites in the guest molecules and cyclodextrins varying in size, correlations between cavity size, complex formation constants, and inclusion complex geometry were explored. The effects of complexation on the UV and proton NMR spectra of purine nucleosides were related to the inclusion structure and cavity microenvironment. The rates of isotopic exchange of the H-C(8) hydrogen in adenosine and adenosine arabinoside were measured by NMR spectroscopy at 37° C and at various concentrations of β-cyclodextrin (β-CD) and hydroxypropyl-β-CD. The marked inhibition of the exchange rates observed upon the formation of inclusion complexes was also related to inclusion structure. All of the data suggest that, in complexes with β-cyclodextrin and its hydroxypropyl derivatives, the purine residue is oriented in the complex with its short axis nearly parallel to the C 7 axis of the β-CD cavity.