Novel mass spectrometric methods for the characterization of pharmaceutical compounds, and for the investigation of biradical-induced damage on protein components

Mingkun Fu, Purdue University

Abstract

The ability to rapidly identify unknown mixture components is of great interest to pharmaceutical industry. Mass spectrometry provides a fast and sensitive tool for mixture analysis. Many mass spectrometric methods, such as tandem mass spectrometry based on collision-activated dissociation and H/D exchange reactions, have been used for obtaining structural information on mixture components. However, these techniques don’t always allow the unambiguous identities of the functional groups in mixture components. The objective of this thesis was to develop ion-molecule reaction-based methods for the identification of functional groups in protonated unknown pharmaceuticals by mass spectrometry. In this thesis, methodologies have been developed for the identification of several monofunctional (primary alcohols, secondary alcohols, tertiary alcohols, primary amines, secondary amines, and tertiary amines) and basic bifunctional analytes (i.e., aliphatic diamines) by using a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Furthermore, novel methodology has been developed for the differentiation of protonated ortho-, meta- and para-isomers of phenylene- and toluenediamines by using FT-ICR, triple quadrupole, and linear quadrupole ion trap mass spectrometers. Another application of gas-phase ion-molecule reactions involves obtaining intimate details of reaction mechanisms (e.g., radical ion reactions) that are difficult to study by other experimental approaches. This is because gas-phase ion-molecule reactions in high vacuum are not hampered by solvation and ion pairing effects as in solution. In this thesis, the reactivity of a positively charged aromatic σ,σ,-biradical (N-methyl-6,8-didehydroquinolinium cation) toward six aliphatic amino acids and fifteen dipeptides was examined via ion-molecule reactions in a (FT-ICR) mass spectrometer coupled with the laser-induced acoustic desorption (LIAD) technique. It was found that both the backbone and the side chains of amino acids and peptides are attacked by the biradical. Furthermore, the peptides’ amino acid sequence was found to play an important reactivity controlling role.

Degree

Ph.D.

Advisors

Kenttamaa, Purdue University.

Subject Area

Analytical chemistry

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