Chiral studies of non-covalent complexes by electrospray ionization (ESI) Fourier transform mass spectrometry (FTMS)

The introductory chapter touches upon the significance chirality carries in life, presenting cyclodextrin and maltoheptaose as hosts for the enantiomeric studies carried out throughout this work.; The chirality studies are based solely on mass spectrometry, employing a gas-phase exchange reaction between a non-covalent complex, [Host:Guest+H] +, and a base. The theory and instrumentation of electrospray ionization (ESI) source and Fourier transform mass spectrometry (FTMS) are also included.; The second chapter introduces the method of Peak Height Analysis, for determining enantiomeric excess in mixtures of amino acids, based solely mass spectrometry. It is based on a gas-phase ion/molecule reaction, between a protonated complex and an alkyl amine is used. The complex is comprised of a β-cyclodextrin host and an amino acid guest that is replaced by the alkyl amine. The rates of the guest exchange reaction vary with the chirality of the amino acid. A calibration curve is produced and the fractions of the D isomer in the test mixtures are determined.; Chapter three presents practical applications of the Peak Height Analysis method in the previous chapter. Protonated complexes involving cyclodextrin hosts and pharmaceuticals as the guests are used. The pharmaceutical compounds include DOPA, amphetamine, ephedrine, and penicillamine. Enantiomeric excess was determined via this method. To understand the nature of the interactions, molecular dynamics calculations are used.; In chapter four, the enantiomeric excess determination method is extended to an ion trap mass spectrometer. IITMS is employed to analyze chiral guest-exchange reactions in gas-phase complexes of amino acids and cyclodextrin. Enantioselectivity was obtained with several amino acids. The results are consistent with those obtained earlier with Fourier transform mass spectrometry (FTMS). The two mass analyzers are compared with regard to enantiomeric analysis.; Chapter five takes a more theoretical approach, using the enantioselective exchange reaction to study and understand the enantiomeric complex behavior in the gas phase using only mass spectrometry. Protonated complexes comprised of guest peptides with permethylated hosts cyclodextrin and maltoheptaose are produced in the gas phase and reacted with a gaseous alkyl amine. Influence of both host and guest size, of alkyl amine gas-phase basicity, and other factors are investigated. Molecular dynamics calculations are used to aid in elucidating reactivities of the exchange reactions.