Kinetic method for the simultaneous chiral analysis of different amino acids in mixtures

Abstract

The kinetic method has been extended to enantiomeric excess (ee) determinations on amino acids present in mixtures. Singly charged trimeric clusters [Cu(II)(ref*)(2)(A(m)) - H](+) are readily generated by electrospraying solutions containing Cu(II), a chiral reference ligand (ref*), and the amino acids (analytes A(m), m = 1-3). A trimeric cluster ion for each amino acid is individually mass-selected and then collisionally activated to cause dissociation by competitive loss of either the reference ligand or the analyte. For each analyte in the mixture, as shown from separate experiments, the logarithm of the ratio of the fragment abundances for the complex containing one enantiomer of this analyte expressed relative to that for the fragments of the corresponding complex containing the other enantiomer is linearly related to the enantiomeric composition of the amino acid. Formation and dissociation of each trimeric complex ion are shown to occur independently of the presence of other analytes. Chiral selectivity appears to be an intrinsic property and the chiral selectivity R(chiral(m)) measured from the mixture of analytes is equal to R(chiral) measured for the pure analyte. The sensitive nature of the methodology and the linear relationship between the logarithm of the fragment ion abundance ratio and the optical purity, characteristic of the kinetic method, allow the determination of chiral impurities of less than 2% ee in individual compounds present in mixtures by simply recording the ratios of fragment ion abundances in a tandem mass spectrum.

Distinction and quantitation of sugar isomers in ternary mixtures using the kinetic method

“…Some cases of nonlinearity have previously been reported [23,33,34]. The basis for enantiomer (or isomer) mixture analysis using the kinetic method is the independent formation of the individual trimeric complex ions [35]. The relative abundances of…”

Recognition and quantification of binary and ternary mixtures of isomeric peptides by the kinetic method: metal ion and ligand effects on the dissociation of metal-bound complexes

“…It has also been demonstrated for chiral analysis of amino acids [23,33,34], ␣-hydroxy acids [25,35], chiral peptides [36], sugars [37], an antiviral nucleoside drug [24], and oxazolidinones (in this last case, by using a novel variant of the kinetic method that uses fixed ligands [38]). The kinetic method has also been applied to chiral quantification of amino acids in mixtures [39]. It is worthwhile pointing out that eq 10 also gives physical meaning to the calibration curves: The slope is equal to the natural logarithm of the isomeric selectivity and the intercept is the natural logarithm of the branching ratio when the analyte is pure N. It is clear that the larger the isomeric selectivity, the larger is the contribution to the measured ratio R upon unit change in isomeric molar fraction, and the higher accuracy that will be obtained, provided the abundance of two fragments can be accurately measured simultaneously.…”

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].…”