Electron Transfer versus Proton Transfer in Gas-Phase Ion/Ion Reactions of Polyprotonated Peptides

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Unmodified and amide nitrogen methylated peptide cations were reacted with azobenzene radical anions to study the utility of electron transfer dissociation (ETD) in analyzing N-methylated peptides. We show that methylation of the amide nitrogen has no deleterious effects on the ETD process. As a result, location of alkylation on amide nitrogens should be straightforward. Such a modification might be expected to affect the ETD process if hydrogen bonding involving the amide hydrogen is important for the ETD mechanism. The partitioning of the ion/ion reaction products into all of the various reaction channels was determined and compared for modified and unmodified peptide cations. While subtle differences in the relative abundances of the various ETD channels were observed, there is no strong evidence that hydrogen bonding involving the amide nitrogen plays an important role in the ETD process. (J Am Soc

Section: Resultsmentioning

confidence: 99%

Electron transfer dissociation of amide nitrogen methylated polypeptide cations

Crizer

McLuckey

2009

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“…A parameterized expression for H 12 described by Olson and coworkers [61,62] and based on data collected for the reactions of a number of relatively small singly charged ions was used recently in an examination of parameters that affect proton transfer and electron-transfer in ion/ion reactions of polypeptide cations [20]. This expression allows for an estimation of the coupling matrix based upon EA and RE values:…”

Section: Qualitative Trends In Product Partitioningmentioning

confidence: 99%

“…Ion/ion reactions can be generally categorized into three types: charge-transfer (including proton and electron-transfer), complex formation, and metal cation exchange. Careful choice of reagents for ion/ion reactions can provide some control over the extent to which each of these reaction pathways contributes to the ion/ion reaction products observed [19,20]. Factors that play important roles in determining the relative contributions of these reaction pathways are the reactant identities, the charges of the reactant ions, and the reaction exothermicity.…”

mentioning

confidence: 99%

Gas-phase ion/ion reactions of transition metal complex cations with multiply charged oligodeoxynucleotide anions

Barlow

Hodges

Xia

et al. 2008

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Multiply deprotonated hexadeoxyadenylate anions, (A 6 ϪnH) nϪ , where n ϭ 3-5, have been subjected to reaction with a range of divalent transition-metal complex cations in the gas phase. The cations studied included the bis-and tris-1,10-phenanthroline complexes of Cu II , Fe II , and Co II , as well as the tris-1,10-phenanthroline complex of Ru II . In addition, the hexadeoxyadenylate anions were subjected to reaction with the singly charged Fe III and Co III N,N=-ethylenebis(salicylideneiminato) complexes. The major competing reaction channels are electron-transfer from the oligodeoxynucleotide anion to the cation, the formation of a complex between the anion and cation, and the incorporation of the transition-metal into the oligodeoxynucleotide. The latter process proceeds via the anion/cation complex and involves displacement of the ligand(s) in the transition-metal complex by the oligodeoxynucleotide. Competition between the various reaction channels is governed by the identity of the transition-metal cation, the coordination environment of the metal complex, and the oligodeoxynucleotide charge state. In the case of the divalent metal phenanthroline complexes, competition between electron-transfer and metal ion incorporation is particularly sensitive to the coordination number of the reagent metal complexes. Both electron-transfer and metal ion incorporation occur to significant extents with the bis-phenanthroline ions, whereas the trisphenanthroline ions react predominantly by metal ion incorporation. To our knowledge this work reports the first observations of the gas-phase incorporation of multivalent transition-metal cations into oligodeoxynucleotide anions and represents a means for the selective incorporation of transition-metal counter-ions into gaseous oligodeoxynucleotides. [6 -8] have allowed the formation of gas-phase ions of biopolymers, including oligodeoxynucleotides (ODNs), making these ions amenable to study by mass spectrometry. Like peptides and proteins, ODNs are amphoteric, [9] allowing formation of either positively or negatively charged ions. Formation of negatively charged oligonucleotides is quite facile using ESI and, as a result, negatively charged ODN ions have been the most widely studied [9]. Oligodeoxynucleotide ions with bound metals formed by MALDI or ESI, especially those containing transition metals, have shown fragmentation behavior, which is distinct and complementary to that of ions devoid of metals [6 -8].The study of the interaction of transition metals with DNA is of critical importance, given the variety of roles such interactions fulfill. Transition-metal complexes display nuclease activity and consequently complexes such as (methidium-propyl-EDTA)iron(II) have been utilized as footprinting agents [10]. Ruthenium(II) complexes have been extensively examined as spectroscopic probes of local DNA structure [11,12]. The mechanism of action of the chemotherapeutic agent cisplatin involves binding to DNA to prevent replication [13][14][15]. Mass spectrometry has been u...

“…The charge inverted LKRApYGL-NH 2 [M ϩ 2H] 2ϩ ions were then isolated by using Q3 in the RF/DC mode and subjected to the next step of ion/ion reaction with azobenzene molecular anions (Figure 4d), which were generated through negative APCI and isolated by Q1 in the RF/DC mode when transmitted through the Q1 quadrupole. Azobenzene was chosen as the ETD reagent species because it has been shown previously to lead to relatively high ETD efficiency when reacting with a triply protonated model peptide [45]. Figure 4e shows the electrontransfer ion/ion reaction products after mutual storage of the isolated LKRApYGL-NH 2 [M ϩ H] 2ϩ ions via charge inversion shown in Figure 4c and [DAB ϩ 7H] 7ϩ ions in Figure 4d for 350 ms. Electron-transfer from azobenzene anions to doubly protonated LKRApYGL-NH 2 gave rise to c-and/or z-type fragments at every inter-residue bond as well as fragments from arginine side-chain loss.…”

Section: Sequential Proton-transfer Charge Inversion and Electron-tramentioning

confidence: 99%

A pulsed triple ionization source for sequential ion/ion reactions in an electrodynamic ion trap

Liang

Han

Xia

et al. 2007

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A pulsed triple ionization source, using a common atmosphere/vacuum interface and ion path, has been developed to generate different types of ions for sequential ion/ion reaction experiments in a linear ion trap-based tandem mass spectrometer. The triple ionization source typically consists of a nano-electrospray emitter for analyte formation and two other emitters, an electrospray emitter and an atmospheric pressure chemical ionization emitter or a second nano-electrospray emitter for formation of the two different reagent ions. The three emitters are positioned in a parallel fashion close to the sampling orifice of the tandem mass spectrometer. The potentials applied to each emitter are sequentially pulsed so that desired ions are generated separately in time and space. Sequential ion/ion reactions take place after analyte ions of interest and different set of reagent ions are sequentially injected into a linear ion trap, where axial trapping is effected by applying an auxiliary radio frequency voltage to the end lenses. The pulsed triple ionization source allows independent optimization of each emitter and can be readily coupled to any atmospheric pressure ionization interface with no need for instrument modifications, provided the potentials required to transmit the ion polarity of interest can be synchronized with the emitter potentials. Several sequential ion/ion reactions examples are demonstrated to illustrate the analytical usefulness of the triple ionization source in the study of gas-phase ion/ion chemistry. . Electron-transfer reactions appear to be a highly useful means for deriving the primary structure information of peptides and proteins [7][8][9][10][11].Most ion/ion reaction studies involving biomolecules are conducted in one of two ways. The first approach is to mix the oppositely charged reactant ions at or near atmospheric pressure before sampling ions into a mass spectrometer. The second approach is to admit the ions of opposite polarity into an electrodynamic ion trap for subsequent mutual storage and reaction. The former approach has employed a spray ionization method as one of the ion sources and either a discharge [12][13][14], radioactive source [15,16], or another spray ionizer [17] as the second ion source. In this approach, the ion sources have been operated simultaneously and, in general, continuously. This approach avoids the need for instrument modification to accommodate an additional ion source interface but it is not conducive to MS n studies. In the latter approach, electrodynamic ion traps, either a quadrupole ion trap or a linear ion trap (LIT), are used as reaction vessels for ion/ion reactions due to their ability to store oppositelycharged ions simultaneously [18] as well as their ion isolation and MS n functionalities [19].Sequential ion/ion reactions have been found to be useful in a number of applications in the analysis of peptides and proteins. One example is the increase of the absolute charge state of a polypeptide ion, which has been achieved via two sequential i...