Gas phase studies of ammonium-cyclodextrin compounds using Fourier transform ion cyclotron resonance

Cyclodextrins (CDs) are cyclic oligosaccharides composed of 6, 7, or 8 glucose molecules (alpha-, beta-, or gamma-cyclodextrin, respectively) which are used widely in industry due to their ability to form inclusion complexes with a variety of molecules in aqueous solution. Much speculation has been made as to whether inclusion complexes form as a result of hydrophobic interactions between guest molecules and the inner hydrophobic cavity of the CDs in water. Fourier transform ion cyclotron resonance (FTICR) mass spectrometry was used to study adducts of cyclodextrins with various amines in the gas phase. Protonated cyclodextrins were generated using electrospray ionization, and were allowed to react with neutral amines. Adducts of each amine studied were observed to form with all three cyclodextrins. Equilibrium constants were measured for the exchange of neutral amines on protonated CD molecules. Size and shape dependent trends, especially with bulkier amines, suggest inclusion complex formation. Molecular modeling studies also support the formation of inclusion complexes rather than nonspecific adducts, and suggest that solvation of the charged guest by the CD host provides a large driving force for the formation of inclusion complexes, which are then stabilized by van der Waals interactions between the host and the guest. A second series of experiments was performed using gas phase hydrogen/deuterium exchange of protonated cyclodextrins and cyclodextrin-amine complexes with D2O. The protonated cyclodextrins have a rapid rate of exchange that slows by more than a factor of 10 when an amino guest is added. The amino groups of the guests are expected to have significantly higher gas phase basicities than the hydroxyl sites on the cyclodextrins or the deuterating agent, accounting for the observed decrease in exchange rates for cyclodextrin-amine complexes. Observed differences in the alpha- versus beta- versus gamma-cyclodextrin exchange rates suggest an exchange mechanism dependent upon the size of the cyclodextrin ring and its gas phase conformation. (C) 1999 Elsevier Science B.V.