Characterization of gas-phase chiral reactions by electrospray ionization (ESI) Fourier transform mass spectrometry (FTMS)

The first chapter provides a brief introduction on the importance of noncovalent complexes in biological and biochemical processes. Cyclodextrins are presented as ideal, yet simple model systems for the study of noncovalent complexes. Chiral selectivity and the challenges it poses for mass spectrometry is also briefly discussed. The theory and instrumentation of electrospray ionization (ESI) Fourier transform mass spectrometry (FTMS) is also presented.; The second chapter describes a novel gas-phase, guest exchange reaction of amino acids complexed to a cyclodextrin host. The cyclodextrin:amino acid complex is allowed to react with an alkyl amine in the analyzer cell of a Fourier transform mass spectrometer. The amino acid guest is replaced by the amine and the exchange rates are found to differ according to the chirality of the amino acid. Consequently, this method is proposed as a fast and sensitive method for determining enantiomeric excess of amino acids.; Chapter three tackles a more fundamental question—the existence of inclusion complexes in the gas phase. Although the existence of cyclodextrin inclusion complexes in solution is well characterized and documented, its existence in the gas phase remains controversial. In this chapter we present theoretical and experimental evidences, based on the guest-exchange reactions (chapter 2), for the presence of gas-phase inclusion complexes.; Chapter four discusses the validity of the “three-point interaction model” as a means of achieving chiral selectivity in gas-phase cyclodextrin complexes. Hydrogen bonding, which is deemed important in the three-point interaction model, is investigated with amino acid esters. The effect of chiral amines on chiral selectivity and the use of linear sugars as chiral selector are also evaluated.; Chapter five describes the use of heated capillary dissociation (HCD) with ESI-FTMS to probe the thermal stabilities of CD:AA complexes in the gas phase. Two dipeptides, Gly-phe and Phe-gly, are used in this study for comparison with the amino acids. The results suggest that the aromatic amino acid is preferentially included inside the CD cavity. Molecular modeling (MM) calculations were carried out in order to elucidate and to gain some insight into the molecular interactions and structural factors that govern the formation of inclusion complexes.