Enantiomeric Analysis of Pharmaceutical Compounds by Ion/Molecule Reactions

Abstract

Protonated complexes involving cyclodextrin hosts and guest compounds that are pharmacologically important are produced in the gas phase and reacted with a gaseous amine. The guest is exchanged to produce a new protonated complex with the amine. The reaction is enantioselective and is used to develop a method for determining enantiomeric excess using only mass spectrometry. The pharmaceutical compounds include DOPA, amphetamine, ephedrine, and penicillamine. The presence of more than one reacting species is observed with DOPA and penicillamine. Molecular dynamics calculations are used to understand the nature of the interactions and the possible source of the variations in the reactivities.

Chiral differentiation of some cyclopentane and cyclohexane β-amino acid enantiomers through ion/molecule reactions

“…The reaction plots of the enantiomeric ␤-amino acids show bimodal behavior showing the existence of fast (k fast ) and slow (k slow ) reacting complexes. The reason for this kind of behavior might be due to possibility that more than one ion population is present and/or there are some "hot" segments in ion population, which are reacting quickly away [34,42]. This same kind of behavior was also observed in our earlier studies of differentiation of diastereomeric ␤-amino acids, for example cyclopentane and cyclohexane ␤-amino acids, when host-guest complexes and ion/ molecule reactions were utilized [38,43].…”

“…In the field of host-guest complexes and ion/molecule reactions, especially Dearden et al have utilized chiral crown ether derivatives in chiral recognition of enantiomeric amines [29 -31]. Moreover, Lebrilla et al have utilized cyclodextrins as host compounds when differentiating enantiomeric ␣-amino acids, pharmaceutical compounds, and peptides [32][33][34][35].…”

Structural relationships in small molecule interactions governing gas-phase enantioselectivity and zwitterionic formation

“…Using this reaction, we probed the structure of gas-phase complexes [16,18,19] and determined enantiomeric excess of amino acids and pharmaceutical compounds [14,20,21]. Subsequently, other gas-phase methods have been used for determining enantiospecificity [22].…”

The Physical Chemistry of Chirality

“…The weak interactions involved in chiral discrimination (49). Several laboratories are now utilizing similar gas phase host/guest chemistry as a mass spectrometric analytical method to detect enantiomeric excess (50)(51)(52). Electrospray ionization or fast-atom bombardment methods are used to introduce the samples to the spectrometer.…”