Gas-phase ion -molecule reactions in mass spectrometric studies of phenyl radical-induced damage on peptides and in the characterization of functional groups in unknown compounds

Sen Li, Purdue University

Abstract

Some biomolecules, such as DNA, RNA and proteins, undergo aggregation and degradation upon phenyl radical attack. However, the mechanisms of these reactions still remain unknown. Therefore, the reactivity and susceptibility of di-, tri-, tetra-, and larger peptides toward phenyl radical attack was examined via ion-molecule reactions in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer coupled with the laser-induced acoustic desorption technique. Hydrogen atom abstraction dominates the reactions for most of the peptides. NH2-abstraction from the N-terminus is only favorable for the more polar phenyl radicals. Furthermore, peptides containing aromatic side chains, SH or SCH3 groups, or disulfide bonds are more susceptible toward phenyl radicals than other peptides. However, the 3-D structure of pressinoic acid was found to have a significant impact on its reactivity toward phenyl radicals. Another application of ion-molecule reactions is to structurally characterize unknown components in mixture. Tandem mass spectrometry based on collision-activated dissociation can provide structural information; however, the identities of the functional groups in mixture components often remain uncertain. In this thesis research, ion-molecule reaction based methods were developed in Fourier transform ion cyclotron resonance mass spectrometers for the identification of oxygen functionalities in mono- and bifunctional compounds. The neutral reagent chosen for this research, trimethylborate (TMB), derivatizes the protonated analytes through an addition-elimination reaction. Further structural information was obtained through sustained off-resonance irradiation collision-activated dissociation (SORI-CAD). These methodologies were successfully implemented on a triple quadrupole mass spectrometer, which indicates that they are feasible in mass spectrometers other than FT-ICRs. Further, the methodology was tested for the identification of the functionalities in protonated amino acids, which contain two or three functionalities. These functionalities can be identified and counted by ion-molecule reactions with neutral TMB combined with SORI-CAD.

Degree

Ph.D.

Advisors

Kenttamaa, Purdue University.

Subject Area

Analytical chemistry

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