File Download
 
 
Supplementary

Postgraduate Thesis: Gas-phase formation, isomerization and dissociation of peptide radicalcations: energetics, dynamics, and mechanisms
  • Basic View
  • Metadata View
  • XML View
TitleGas-phase formation, isomerization and dissociation of peptide radicalcations: energetics, dynamics, and mechanisms
 
AuthorsSong, Tao
宋涛
 
Issue Date2012
 
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
 
AbstractUnderstanding the dissociation of odd-electron peptide radical cations is of great importance for the analytical applications of biological mass spectrometry because their diverse array of fragmentation pathways provides structural information to supplement that from even-electron protonated peptides—allowing peptide sequencing and, ultimately, protein identification. Nevertheless, the mechanisms of peptide radical formation and dissociation remain largely unexplored. In the studies reported in this Thesis, peptide radical cations (M?+) were generated through one-electron transfer (ET) in collision-induced dissociation (CID) of [CuII(L)M]?2+ (L = auxiliary ligand; M = peptide) complexes. Competitive dissociative pathways were circumvented experimentally through judicious selection of the macrocyclic auxiliary ligand, allowing the formation of a broad range of M?+ species. Chapter 3.1 examines the competition between proton transfer (PT) and ET within [CuII(L)His]?2+ complexes with L = dien (an open-chain ligand), or L = 9-aneN3 (the macrocyclic analogue of dien). Density functional theory (DFT) calculations revealed that macrocyclic ligand (9-aneN3) facilitates M?+ formation by maintaining similar ET barriers with open-chain ligand (dien), but substantially increasing PT barriers. Studying and understanding the fragmentations of M?+ species is fundamentally important and a formidable challenge—both charge-directed and radical-driven fragmentations play important roles, in a competitive manner, in the dissociations of M?+ species. Chapters 3.2-3.4 were built upon successful gas phase syntheses of a wide variety of M?+ species. Chapter 3.2 reports the novel Cβ–Cγ bond cleavage of tryptophan residues in the dissociations of various tryptophan-containing M?+ species, resulting in a neutral 116-Da loss; this process is an α-radical–induced fragmentation. Substitution of the tryptophan residue by a 1-methyltryptophan residue revealed that the 116-Da neutral species is a radical with an unpaired electron on the indole nitrogen atom. Chapter 3.3 describes a systematic examination of tryptophan-containing model systems, both with and without basic residues, to unveil the mechanisms of Cβ–Cγ bond cleavages. M?+ species containing non-basic residues undergo protonation of the γ-carbon atom of the tryptophan residue, thereby weakening the Cβ–Cγ bond and facilitating its cleavage. The formation of [1H-indole]?+ (m/z 117) or [M – CO2 – 116]+ ions is a competition between two incipient fragments for the proton in a dissociating proton-bound dimer. In basic residue containing M?+ species, the proton is tightly sequestered by the basic side chain, resulting in more accessible radical migration barriers prior to subsequent bond cleavages; DFT calculations supported the notion that the charge-remote radical-driven pathway is more favorable than the proton-driven process by 6.2 kcal/mol. Selective radical-induced fragmentations were then used to investigate the radical propagation processes occurring via hydrogen atom transfers—in particular, for Cα–C bond cleavages leading to the formation of an+ ions. The energetics and kinetics of the dissociations of [RGn–2FG7–n – CO2]?+ (n = 2–6) with well-defined C-terminal α-radicals were determined by RRKM modeling of surface-induced dissociation experiments and DFT calculations, revealing that radical propagations in peptide radical cations are not necessarily stepwise processes.
 
AdvisorsChu, IK
 
DegreeDoctor of Philosophy
 
SubjectPeptides - Analysis.
Cations.
 
Dept/ProgramChemistry
 
DC FieldValue
dc.contributor.advisorChu, IK
 
dc.contributor.authorSong, Tao
 
dc.contributor.author宋涛
 
dc.date.hkucongregation2012
 
dc.date.issued2012
 
dc.description.abstractUnderstanding the dissociation of odd-electron peptide radical cations is of great importance for the analytical applications of biological mass spectrometry because their diverse array of fragmentation pathways provides structural information to supplement that from even-electron protonated peptides—allowing peptide sequencing and, ultimately, protein identification. Nevertheless, the mechanisms of peptide radical formation and dissociation remain largely unexplored. In the studies reported in this Thesis, peptide radical cations (M?+) were generated through one-electron transfer (ET) in collision-induced dissociation (CID) of [CuII(L)M]?2+ (L = auxiliary ligand; M = peptide) complexes. Competitive dissociative pathways were circumvented experimentally through judicious selection of the macrocyclic auxiliary ligand, allowing the formation of a broad range of M?+ species. Chapter 3.1 examines the competition between proton transfer (PT) and ET within [CuII(L)His]?2+ complexes with L = dien (an open-chain ligand), or L = 9-aneN3 (the macrocyclic analogue of dien). Density functional theory (DFT) calculations revealed that macrocyclic ligand (9-aneN3) facilitates M?+ formation by maintaining similar ET barriers with open-chain ligand (dien), but substantially increasing PT barriers. Studying and understanding the fragmentations of M?+ species is fundamentally important and a formidable challenge—both charge-directed and radical-driven fragmentations play important roles, in a competitive manner, in the dissociations of M?+ species. Chapters 3.2-3.4 were built upon successful gas phase syntheses of a wide variety of M?+ species. Chapter 3.2 reports the novel Cβ–Cγ bond cleavage of tryptophan residues in the dissociations of various tryptophan-containing M?+ species, resulting in a neutral 116-Da loss; this process is an α-radical–induced fragmentation. Substitution of the tryptophan residue by a 1-methyltryptophan residue revealed that the 116-Da neutral species is a radical with an unpaired electron on the indole nitrogen atom. Chapter 3.3 describes a systematic examination of tryptophan-containing model systems, both with and without basic residues, to unveil the mechanisms of Cβ–Cγ bond cleavages. M?+ species containing non-basic residues undergo protonation of the γ-carbon atom of the tryptophan residue, thereby weakening the Cβ–Cγ bond and facilitating its cleavage. The formation of [1H-indole]?+ (m/z 117) or [M – CO2 – 116]+ ions is a competition between two incipient fragments for the proton in a dissociating proton-bound dimer. In basic residue containing M?+ species, the proton is tightly sequestered by the basic side chain, resulting in more accessible radical migration barriers prior to subsequent bond cleavages; DFT calculations supported the notion that the charge-remote radical-driven pathway is more favorable than the proton-driven process by 6.2 kcal/mol. Selective radical-induced fragmentations were then used to investigate the radical propagation processes occurring via hydrogen atom transfers—in particular, for Cα–C bond cleavages leading to the formation of an+ ions. The energetics and kinetics of the dissociations of [RGn–2FG7–n – CO2]?+ (n = 2–6) with well-defined C-terminal α-radicals were determined by RRKM modeling of surface-induced dissociation experiments and DFT calculations, revealing that radical propagations in peptide radical cations are not necessarily stepwise processes.
 
dc.description.naturepublished_or_final_version
 
dc.description.thesisdisciplineChemistry
 
dc.description.thesisleveldoctoral
 
dc.description.thesisnameDoctor of Philosophy
 
dc.identifier.hkulb4786955
 
dc.languageeng
 
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)
 
dc.relation.ispartofHKU Theses Online (HKUTO)
 
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.source.urihttp://hub.hku.hk/bib/B47869550
 
dc.subject.lcshPeptides - Analysis.
 
dc.subject.lcshCations.
 
dc.titleGas-phase formation, isomerization and dissociation of peptide radicalcations: energetics, dynamics, and mechanisms
 
dc.typePG_Thesis
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.advisor>Chu, IK</contributor.advisor>
<contributor.author>Song, Tao</contributor.author>
<contributor.author>&#23435;&#28059;</contributor.author>
<date.issued>2012</date.issued>
<description.abstract>&#65279;Understanding the dissociation of odd-electron peptide radical cations is of great importance for the analytical applications of biological mass spectrometry because their diverse array of fragmentation pathways provides structural information to supplement that from even-electron protonated peptides&#8212;allowing peptide sequencing and, ultimately, protein identification. Nevertheless, the mechanisms of peptide radical formation and dissociation remain largely unexplored. 

In the studies reported in this Thesis, peptide radical cations (M?+) were generated through one-electron transfer (ET) in collision-induced dissociation (CID) of [CuII(L)M]?2+ (L = auxiliary ligand; M = peptide) complexes. Competitive dissociative pathways were circumvented experimentally through judicious selection of the macrocyclic auxiliary ligand, allowing the formation of a broad range of M?+ species. Chapter 3.1 examines the competition between proton transfer (PT) and ET within [CuII(L)His]?2+ complexes with L = dien (an open-chain ligand), or L = 9-aneN3 (the macrocyclic analogue of dien). Density functional theory (DFT) calculations revealed that macrocyclic ligand (9-aneN3) facilitates M?+ formation by maintaining similar ET barriers with open-chain ligand (dien), but substantially increasing PT barriers. 

Studying and understanding the fragmentations of M?+ species is fundamentally important and a formidable challenge&#8212;both charge-directed and radical-driven fragmentations play important roles, in a competitive manner, in the dissociations of M?+ species. Chapters 3.2-3.4 were built upon successful gas phase syntheses of a wide variety of M?+ species. 

Chapter 3.2 reports the novel C&#946;&#8211;C&#947; bond cleavage of tryptophan residues in the dissociations of various tryptophan-containing M?+ species, resulting in a neutral 116-Da loss; this process is an &#945;-radical&#8211;induced fragmentation. Substitution of the tryptophan residue by a 1-methyltryptophan residue revealed that the 116-Da neutral species is a radical with an unpaired electron on the indole nitrogen atom. Chapter 3.3 describes a systematic examination of tryptophan-containing model systems, both with and without basic residues, to unveil the mechanisms of C&#946;&#8211;C&#947; bond cleavages. M?+ species containing non-basic residues undergo protonation of the &#947;-carbon atom of the tryptophan residue, thereby weakening the C&#946;&#8211;C&#947; bond and facilitating its cleavage. The formation of [1H-indole]?+ (m/z 117) or [M &#8211; CO2 &#8211; 116]+ ions is a competition between two incipient fragments for the proton in a dissociating proton-bound dimer. In basic residue containing M?+ species, the proton is tightly sequestered by the basic side chain, resulting in more accessible radical migration barriers prior to subsequent bond cleavages; DFT calculations supported the notion that the charge-remote radical-driven pathway is more favorable than the proton-driven process by 6.2 kcal/mol.

Selective radical-induced fragmentations were then used to investigate the radical propagation processes occurring via hydrogen atom transfers&#8212;in particular, for C&#945;&#8211;C bond cleavages leading to the formation of an+ ions. The energetics and kinetics of the dissociations of [RGn&#8211;2FG7&#8211;n &#8211; CO2]?+ (n = 2&#8211;6) with well-defined C-terminal &#945;-radicals were determined by RRKM modeling of surface-induced dissociation experiments and DFT calculations, revealing that radical propagations in peptide radical cations are not necessarily stepwise processes.</description.abstract>
<language>eng</language>
<publisher>The University of Hong Kong (Pokfulam, Hong Kong)</publisher>
<relation.ispartof>HKU Theses Online (HKUTO)</relation.ispartof>
<rights>The author retains all proprietary rights, (such as patent rights) and the right to use in future works.</rights>
<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<source.uri>http://hub.hku.hk/bib/B47869550</source.uri>
<subject.lcsh>Peptides - Analysis.</subject.lcsh>
<subject.lcsh>Cations.</subject.lcsh>
<title>Gas-phase formation, isomerization and dissociation of peptide radicalcations: energetics, dynamics, and mechanisms</title>
<type>PG_Thesis</type>
<identifier.hkul>b4786955</identifier.hkul>
<description.thesisname>Doctor of Philosophy</description.thesisname>
<description.thesislevel>doctoral</description.thesislevel>
<description.thesisdiscipline>Chemistry</description.thesisdiscipline>
<description.nature>published_or_final_version</description.nature>
<date.hkucongregation>2012</date.hkucongregation>
<bitstream.url>http://hub.hku.hk/bitstream/10722/161514/1/FullText.pdf</bitstream.url>
</item>