Gas-Phase Binding of Noncovalent Complexes Between α-cyclodextrin and Amino Acids Investigated by Mass Spectrometry

Abstract

Noncovalent complexes between cyclodextrins and small molecules have been extensively studied recently because of their widespread application in the pharmaceutical industry for chiral and molecular recognition. To date, gas phase noncovalent binding affinities between α-cyclodextrin and amino acids have not been widely investigated. In this study, gas-phase binding of noncovalent complexes between α-CD and amino acids was investigated by electrospray ionization mass spectrometry (ESI-MS), demonstrating the formation of 1:1 stoichiometric noncovalent complexes. The binding of the complexes were further confirmed by collision-induced dissociation by tandem mass spectrometry. Mass spectrometric titrations between α-cyclodextrin and phenylalanine, glutamic acid, and arginine were performed to provide binding constants (lgK_a) as references for competitive ESI-MS. Calibration curves for the complexes of α-cyclodextrin with phenylalanine, glutamic acid, and arginine were plotted. Through competitive ESI-MS, the lgK_a for the complexes of α-CD with aspartic acid, lysine, proline, glycine, alanine, asparagine, cystine, glutamine, histidine, leucine, isoleucine, methionine, serine, threonine, and valine were measured directly. By comparison, it is seen that the measured binding constants for the complexes of α-cyclodextrin with basic amino acids such as arginine and lysine are lower than those for most complexes of neutral amino acids. The chiral selectivity of α-cyclodextrin for L- and D-isomers of methionine, threonine, asparagine, and phenylalanine determined by ESI-MS revealed its application as a chiral selector.

Keywords:

• α-cyclodextrin
• Amino acid
• Binding constants
• Chiral selectivity
• Mass spectrometry
• Noncovalent interactions

Notes

Note: SD and RSD represent standard deviation and relative standard deviation, respectively.

Note: The lgK _a values marked a, b, or c were derived from the equation y_a, y_b, or y_c in Table 3, respectively.

Note: R _chiral is defined by the ratio R _L /R _D and inverse of the values are in parentheses.

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