Chiral resolution of d- and l-amino acids by tandem mass spectrometry of Ni(II)-bound trimeric complexes

Abstract

Mass-selected trimeric cluster ions, [Ni II(A)(ref∗) 2−H] +, where A designates the analyte amino acid and ref∗ designates the chiral reference amino acid, undergo competitive collision-induced dissociation to yield two dimeric clusters with a branching ratio dictated by the stereochemistry of both the analyte and the reference. This branching ratio ( R) is related, using the kinetic method, to an enthalpic term, ΔNi IIBDE, the difference between the formation enthalpies of the two dimeric clusters. Chiral resolution of d- and l-amino acids is directly related to the relative stabilities of the two diastereomeric clusters formed by the dissociation of the Ni(II)-bound trimeric clusters. The dimeric product ions differ in enthalpy by only a few kilojoules per mole, but chiral recognition is achieved for all 19 naturally occurring chiral amino acids, using appropriate reference amino acids. Because there is evidence that the dissociating trimeric clusters may exist in different isomeric forms, the proportion of analyte versus reference amino acids in the mixture was examined to study the effect of this ratio on the success of chiral recognition. The effect was found to be negligible. This suggests that there is an equilibrium between these isomeric clusters, which is governed by thermochemical properties rather than the relative concentrations of the constituent amino acids. A linear correlation was observed between ln( R) and enantiomeric compositions of the analyte as expected from the kinetic method treatment, and the direct measurement of optical purity to within 3% enantiomeric excess was demonstrated. With this new chiral recognition technique, qualitative and quantitative chiral analysis of amino acids is achieved.