Structural relationships in small molecule interactions governing gas-phase enantioselectivity and zwitterionic formation

Abstract

Gas-phase zwitterionic amino acids were formed in complexes of underivatized ␤-cyclodextrin through reactions with a neutral base, n-propylamine. The reaction was performed in the analyzer cell of an electrospray ionization-Fourier transform mass spectrometer. Most of the natural amino acids were studied with three cyclodextrin hosts including ␣-, ␤-, and ␥-cyclodextrin to understand better the structural features that lead to the stabilization of the zwitterionic complexes. Molecular dynamics calculations were performed to provide insight into the structural features of the complexes. The rate constants of the reactions were obtained through kinetic plots. Examination of both L-and D-enantiomers of the amino acid showed that the reaction was enantioselective. The reaction was then employed to analyze mixtures of Glu enantiomers naturally occurring in the bacteria Bacillus licheniformis. (J Am Soc Mass Spectrom 2006, 17, 442-452)

Chiral differentiation of some cyclopentane and cyclohexane β-amino acid enantiomers through ion/molecule reactions

“…This same kind of behavior was also observed in our earlier studies of differentiation of diastereomeric ␤-amino acids, for example cyclopentane and cyclohexane ␤-amino acids, when host-guest complexes and ion/ molecule reactions were utilized [38,43]. Moreover, Lebrilla et al have observed this same kind of behavior, especially when studying some trimeric complexes [40,41]. It is assumed that with short reaction times, trimeric complexes are kinetically favored.…”

“…They assumed that these trimeric complexes have a zwitterionic nature, in which the positive charge of the protonated amine is coordinated with the carboxyl group of the amino acid. Moreover, the zwitterionic amino acids are stabilized through hydrogen bonding to the lower rim of cyclodextrin [41]. In this study, however, this phenomenon and the possible structures of trimeric complexes were not further speculated on.…”

“…The trimeric complex consists of the host molecule, the enantiomer of interest, and triethylamine ([Host:␤-AC:Reagent ϩ H] ϩ ). Lebrilla et al noticed and studied similar kinds of trimeric complexes when they separated ␣-amino acid enantiomers using host-guest complexes and ion/molecule reactions [40,41]. They assumed that these trimeric complexes have a zwitterionic nature, in which the positive charge of the protonated amine is coordinated with the carboxyl group of the amino acid.…”

“…It is assumed that with short reaction times, trimeric complexes are kinetically favored. In the case of longer reaction times, the reaction pathway forming the new host-guest complex persists after zwitterion formation has diminished [41]. Because of this kind of behavior, the enantioselectivities are calculated based on both fast and slow reaction complexes.…”

Chiral Differentiation of Amino Acids by In-Source Collision-Induced Dissociation Mass Spectrometry

“…[3][4][5] e second one is to investigate the exchange rate in the reaction of the diastereomeric host-guest complexes with a neutral reagent (guest). [6][7][8][9][10] e third one is to compare the di erence in fragmentation pattern caused by collisioninduced dissociation (CID) of the diastereomeric adduct ions. [11][12][13][14][15][16][17][18][19][20] Among these di erent chiral analysis methods, the kinetic method has been proven to be the most widely applied one.…”