Kinetic Resolution of d,l-Amino Acids Based on Gas-Phase Dissociation of Copper(II) Complexes

Abstract

Chiral recognition of d- and l-amino acids is achieved in the gas phase on the basis of the kinetics of competitive fragmentations of trimeric Cu(II)-bound complexes. The singly charged copper(II)-amino acid trimeric cluster ions [A(2)BCu(II) - H](+) dissociate to form [A(2)Cu(II) - H](+) and [ABCu(II) - H](+) upon collision-induced dissociation (CID) in a quadrupole ion trap. The abundance ratios of these fragments depend strongly on the stereochemistry of the ligands in the [A(2)BCu(II) - H](+) complex ion. The kinetic method was used to calculate relative Cu ion affinities (ΔCu(II)') for homo- and heterochiral copper(II)-bound dimeric cluster ions as the indicator of chiral discrimination. Six amino acids of four different types showed chiral distinctions which ranged from 0 to 6.5 kJ/mol in terms of values of ΔCu(II)' with abundance ratios, referenced to the other enantiomer, ranging from 1 to 9.2. Amino acids with aromatic substituents displayed the largest chiral distinction, which correlates well with reported chromatographic results. The methodology presented here provides a sensitive means to study enantiomers by mass spectrometry, and initial results show that it is applicable to measurement of enantiomeric excess.

Peer Reviewed: Chiral analysis by MS

“…If a relatively simple relationship between R and ee can be established, then it is possible to rapidly determine the mixture components by measuring R in a single tandem mass spectrum. A linear relationship between ln R and ee has been observed in various systems and is predicted from kinetic method derivations (13,14). The two cluster ions yield identical products by one fragmentation route and diastereomeric product ions with energies that differ by ⌬(⌬G) chiral by competitive ligand loss fragmentation.…”

“…Several reviews summarize chiral recognition by MS (4,12). This article focuses on quantitative chiral analysis by MS and emphasizes an MS method based on the competitive dissociation of metal ion-bound cluster ions (13,14). It borrows from ligand-exchange chromatography the idea of creating diastereomeric complexes by binding the chiral analyte to a chirally ligated metal center (15).…”

Isomeric Distinction of Small Oligosaccharides: A Bottom-Up Approach Using the Kinetic Method

“…O riginally developed for the determination of thermochemical properties of molecules in the gas phase [1], the kinetic method was further successfully utilized to differentiate and quantify enantiomers in mixture, such as amino acids [2][3][4][5], sugars [6], chiral drugs [7][8][9][10][11], and hormones [12]. For the same classes of compounds, the kinetic method has also proven relevant for the distinction of isomers, as reported for peptides [13][14][15][16] and amino acids [17], monosaccharides [18] and thyroid hormones [19].…”

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

“…Mass spectrometry, instead, can be very fast, sensitive, and sample friendly. Different mass spectrometric methods, especially the kinetic method presented by Cooks et al, have gained much interest in the field of enantiomer differentiation [18,19]. Methods that utilize host-guest complexes and ion/molecule reactions have been used as well [20 -28].…”