Electrospray ionization quadrupole ion trap mass spectrometric study of cyclodextrins and their inclusion complexes

Electrospray ionization (ESI) quadrupole ion trap mass spectrometry was used to characterize three native cyclodextrins (α-, β-, and γ-cyclodextrin (α, β, and γCD)) and a synthetic charged βCD derivative (aminoethanthio(6-monodeoxy-6-mono)-β-CD) (βCDSNH₂). The application of ESI to CD inclusion complexes was investigated.; The ESI mass spectra of all CDs showed multiple charge state distributions. The effects of organic solvent and CD concentration on CD charge state distributions were consistent with analytes bearing permanent charge sites. Increasing the amount of external electrolyte sodium chloride (NaCl) shifted the CD ions to the low charge state in a limited range. The charge state distribution of CD ions can be explained by Fenn's theoretical consideration of the ion evaporation model for the formation of multiply charged macroions. The effect of NaCl electrolyte on the charge distribution was more significant for βCD derivative than that for βCD which was due to its formation of excess charges on the droplet surface. Cluster formation was more severe for the highly soluble βCDSNH₂ than that of native βCD. The possible mechanism for aggregation was enrichment of protonated βCDSNH₂ ions on the droplet surface during the ESI process. This is different from the situation of solute precipitation due to low solubility and evaporation of the solvent by the ESI process. Two reasons are possibly responsible for the phenomena that the charge distribution shifted to the higher charge state with the increasing size of the native CD. One is the reduction of charge repulsion with the CD size as confirmed by the MS/MS experiment; the other is the result of ESI process, itself.; The observation of CD noncovalent associations has the special requirements of solution and instrumental conditions. Solution conditions including organic solvent, type and amount of electrolyte were examined. Instrumental conditions included ESI interface, setting and the operation of the mass analyzer. The results of ESI-MS for the interactions between CDs and three guests (4-nitrophenyl)methanol, 2-(4-nitrophenyl)ethanol and 4-(4-nitrophenyl)butanol reflected solution relative host-guest binding affinity and possible binding structure. The structure of αCD-indole complex in the gas phase was consistent with that in solution phase. However, not all the CD inclusion complexes could be examined by ESI-MS. Lowering the host and guest concentration and adding suitable electrolyte was a useful way for the reduction of nonspecific aggregation. Inclusion complex ions that survived the ESI interface and were detected by mass analyzer required a certain degree of gas-phase stability. The gas-phase stability of a complex ion was affected by the whole inclusion complex structure and the attached charges. ESI-MS is a fast, high sensitivity method that gives directly stoichiometry of the complexes and may provide information complementary or confirmatory to other techniques.