Date of Award

Spring 2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Yu Xia

Committee Chair

Lei Tan

Committee Member 1

Hilkka I. Kenttämaa

Committee Member 2

Scott A. McLuckey

Committee Member 3

Garth J. Simpson

Abstract

Gas-phase radical ion chemistry has attracted increasing research interest from the mass spectrometry (MS) society because it provides new capabilities in bio-analysis which often complements traditional MS methods developed from even-electron ions. Fundamental studies of biomolecule related radical species are essential to broadening the scope of radical chemistry and pushing the frontiers of its analytical applications. This dissertation mainly discusses the gas-phase chemistry of peptide sulfinyl radicals (-SO·), which has been rarely studied before. In order to establish an effective research approach, a method that can generate site-specific peptide sulfinyl radical ion has been developed. This method is based on reactions between OH radicals and disulfide linked peptides at the interface of a nanoelectrospray ionization-MS instrument. The peptide sulfinyl radical ions are thus mass-isolated in MS and its intrinsic chemical properties are investigated via MS approaches including collision-induced dissociation (CID), H/D exchange, and ion/molecule reactions. Theoretical calculations have also been utilized to further explain the experimental phenomena. Different from carbon-centered radical species, sulfinyl radicals exhibit significant proton affinity due to the existence of heteroatoms. Evidence from experimental and theoretical studies clearly show that the duality of a sulfinyl radical to function as a radical or a base is affected by the neighboring amino acid side-chain chemistry within a peptide. For instance, a sulfinyl radical can form proton bridge with the basic side-chain of histidine or arginine, while direct protonation on a sulfinyl radical is observed in the case of a side-chain containing an alkyl or hydroxyl group. This new insight suggests that heteroatom-centered radical species may actively engage in forming proton bridges within proteins. We also manage to generate site-specific glycyl radical in the gas phase utilizing a distinct dissociation pathway of the sulfinyl radical (β-cleavage). This approach enables systematic studies on how the electronic properties of the substituents affect the stability of glycyl type radicals (X-·CH-Y). Overall, our investigations into peptide radical ions have resulted in the establishment of a suite of experimental tools and new knowledge of bio-radical species.

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