Electrospray ionization mass spectrometric study of encapsulation of amino acids by cyclodextrins

Abstract

Electrospray ionization (ESI) mass spectrometry has been used to study inclusion (host-guest) complexes of cyclodextrins (CDs) with amino acids. Host-guest complexes formed in solution are stable for characterization by ESI mass spectrometry: The relative abundances and the stoichiometry of the complexes formed in solution can, thus, be determined in the gas phase. The studies verified that β- and γ-cyclodextrin better accommodate protonated amino acids than α-cyclodextrin, and that chemically modified cyclodextrins such as heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) may show profound improvement in complexation. The preferential formation of DM-β-CD-aromatic amino acid over DM-β-CD-aliphatic amino acid complexes is confirmed by the experiments, and the relative gas-phase stabilities determined by repeller-collimator collision-induced dissociation show an identical trend to the complexation in solution. Although molecular mechanics studies also may predict the encapsulation preference of protonated amino acids by cyclodextrins, only small differences in the total complexation energies are obtained because of the inability of the calculations to consider hydrophobic interactions. An experimental approach based on ESI mass spectrometry is, therefore, more reliable in predicting host-guest interactions that involve cyclodextrins and amino acids than the theoretical calculations that employ molecular mechanics models.