| A novel mass spectrometric method for rapid, accurate chiral recognition and enantiomeric determination is presented. The technique uses electrospray ionization on a commercial ion trap mass spectrometer to form transition metal ion-bound cluster ions that promote enantiospecific interactions. Collision induced dissociation (CID) of the cluster ions yields data that is treated by the kinetic method, a sensitive linear free energy method of treating mass spectrometric results and converting them to thermochemical data. Chiral recognition and enantiomeric measurements of amino acids, peptides, α-hydroxy acids, carbohydrates, and some model chiral drugs, including β-blockers, DOPA, and antiviral nucleoside agents, are demonstrated.; Two quantitative methods, the single ratio (SR) and quotient ratio (QR) methods, are being developed for enantiomeric determination. A two-point calibration curve based on the SR method, allows rapid quantitation of enantiomeric excess of drug mixtures, while a single-point calibration curve can be established using the QR method. The chiral sensitivity of both quantitative methods is such as to allow determination of mixtures with a few percent enantiomeric contamination with accuracy less than 1%ee. The underlying kinetics, thermochemistry and intrinsic chiral interactions that are responsible for chiral distinction are investigated by tandem mass spectrometry and ab initio calculations.; The method is extended to the distinction and quantitative analysis of isomeric mixtures. The analysis of isomeric dipeptides differing in amino acid sequences or residues with the same mass (i.e., a leucine/isoleucine substitution) is demonstrated.; The generality of Eberlin reaction is explored using ambiphilic ions including phosphonium, borinium, silylium, and sulfenium cations. Heterocyclic ions are synthesized by a highly exothermic channel, which proceeds via initial cationic binding to a heteroatom followed by a consecutive ring opening and ring reclosing process. |
