Copper(II)-assisted enantiomeric analysis of D,L-amino acids using the kinetic method: Chiral recognition and quantification in the gas phase

Chiral recognition of D- and L-amino acids is achieved and mixtures of enantiomers quantified in the gas phase, using the kinetics of competitive unimolecular fragmentations of trimeric Cu(II)bound complexes. Singly charged copper(II)-amino acid cluster ions [Cu-II(A)(ref*)(2)-H](+) (A = amino acid; ref* = chiral reference ligand, selected from among the natural alpha -amino acids) undergo competitive collision-induced dissociation (CID) in a quadrupole ion trap to form the dimeric complexes [Cu-II(A)(ref*)-H](+) and [Cu-II(ref*)(2)-H](+). The abundance ratio of these fragment ions depends strongly on the stereochemistry of the ligands in the precursor [Cu-II(A)(ref*)(2)-H](+) complex ion and specifically on the chirality of the analyte amino acid. The chiral selectivity, the ratio of the two fragment ion abundances for the complex containing one enantiomer of analyte expressed relative to that for the fragments of the corresponding complex containing the other enantiomer, ranges from 0.47 to 11. An energy quantity, Delta>(*) over bar *(Delta (CuBDE)-B-II), is predicted and shown to serve as a thermochemical indicator of chiral discrimination; its value is calculated from the fragment ion abundance ratios using the kinetic method of estimating thermochemical quantities from the kinetics of cluster ion dissociation. Large chiral distinctions are observed with all of the natural chiral alpha -amino acids, except cysteine and arginine, by appropriate choice of the reference ligand. The Delta>(*) over bar *(Delta (CuBDE)-B-II) values range from -2.2 to 6.9 kJ/mol. Amino acids with aromatic substituents display the largest chiral distinction, which is consistent with ligand exchange chromatographic results for analogous systems. The structures of the fragment Cu(II) complexes are discussed in the light of the CID behavior of related compounds. The interactions within these ions that might contribute to chiral recognition are rationalized to account for the observed chiral effects. The;sensitive nature of the methodology and the linear relationship between the logarithm of the fragment ion abundance ratio and the optical purity, which is intrinsic to the kinetic method, allows mixtures to be analyzed for small enantiomeric excess (ee) by simply recording ratios of fragment ion abundances in a mass spectrum.