Two Ion/Ion Charge Inversion Steps To Form a Doubly Protonated Peptide from a Singly Protonated Peptide in the Gas Phase

He, Min; McLuckey, Scott A.

doi:10.1021/ja0354521

Cited by 55 publications

(69 citation statements)

References 15 publications

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“…This instrument allows remarkable flexibility with respect to the cation/anion combinations that can be used in a single experiment. Novel experiments that use more than two ion sources have been demonstrated with this device, including the formation of multi-unit protein hetero-complexes in the gas phase [61] and the net increase in the absolute charge of an ion via sequential charge inversion reactions [8,9].…”

Section: Ionization Approaches With 3d Ion Trapsmentioning

confidence: 99%

“…For example, a pulsed triple ionization source, using a common atmospheric/vacuum interface and ion path, has been reported [71] to generate different types of ions for sequential ion/ion reaction experiments in a linear ion trap. Compared to the pulsed dual ESI or ESI/APCI source, the pulsed triple ion source is particularly useful for MS n experiments that use more that one type of reagent ion, such as charge increase via sequential charge inversion reactions [7,8]. The pulsed double or triple ion source holds significant advantages over the SSI source for ion/ion reaction studies in terms of the flexibility to optimize ionization conditions for each ionic species, the wide choice of ion/ion reaction combinations, and superior ionization efficiency.…”

Section: Ionization Approaches With Linear Ion Trapsmentioning

confidence: 99%

“…Associated applications have been demonstrated in mixture analysis, especially with the application of the "ion parking" technique [3] for gas-phase ion concentration and purification [4], the formation of ions that are not directly produced by ESI for subsequent tandem mass spectrometry studies [5], and the reduction of the product ion charge states to singly and doubly charged species, to simplify the interpretation of product ion spectra [6]. Ion/ion reactions that allow for multiple proton transfers in a single encounter can lead to the inversion of charge [7] and two such encounters in series can even lead to a net increase in charge for one of the reactants [8,9], which can be desirable for subsequent structural interrogation [10]. The recent demonstration of ion/ion electron transfer to multiply protonated polypeptides that leads to structurally informative fragmentation, a process known as electrontransfer dissociation (ETD) [11,12], provides a major new structure determination tool in proteomics.…”

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confidence: 99%

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Evolution of instrumentation for the study of gas-phase ion/ion chemistry via mass spectrometry

Xia

McLuckey

2008

J. Am. Soc. Mass Spectrom.

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The scope of gas-phase ion/ion chemistry accessible to mass spectrometry is largely defined by the available tools. Due to the development of novel instrumentation, a wide range of reaction phenomenologies has been noted, many of which have been studied extensively and exploited for analytical applications. This perspective presents the development of mass spectrometry-based instrumentation for the study of the gas-phase ion/ion chemistry in which at least one of the reactants is multiply charged. The instrument evolution is presented within the context of three essential elements required for any ion/ion reaction study: the ionization source(s), the reaction vessel or environment, and the mass analyzer. Ionization source arrangements have included source combinations that allow for reactions between multiply charged ions of one polarity and singly charged ions of opposite polarity, arrangements that enable the study of reactions of multiply charged ions of opposite polarity and, most recently, arrangements that allow for ion formation from more than two ion sources. Gas-phase ion/ion reaction studies have been performed at near atmospheric pressure in flow reactor designs and within electrodynamic ion traps operated in the mTorr range. With ion trap as a reaction vessel, ionization and reaction processes can be independently optimized and ion/ion reactions can be implemented within the context of MS n experiments. Spatial separation of the reaction vessel from the mass analyzer allows for the use of any form of mass analysis in conjunction with ion/ion reactions. Time-of-flight mass analysis, for example, has provided significant improvements in mass analysis figures of merit relative to mass filters and ion traps. The development and evaluation of new tools has clearly been a central activity and contributor to the dramatic advances in the capabilities of mass spectrometry over the past several decades. In this perspective, we relate the evolution of instrumentation for research activities focused on the study and use of ion/ion reactions and offer it as one example of many where progress in an area of science is intimately related to and dependent on the development of instrumentation. It is provided in appreciation for the inspirational example of creativity in instrumentation development [1] provided by Cooks over the years. Electrospray ionization (ESI) [2], among its many contributions, enabled the development of macro-molecule ion/ ion chemistry as a research area. The multiple-charging phenomenon associated with electrospray makes possible the generation of multiply charged reactant ions. This capability leads to the possibility that at least one ion/ion reaction product can retain charge, which makes such a product directly amenable to study with mass spectrometry. In the past two decades, significant progress has been made in understanding and exploring the gas-phase ion/ion chemistry of high mass multiply charged ions. A variety of potential analytical applications have been developed accordingly. Co...

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Section: Ionization Approaches With 3d Ion Trapsmentioning

confidence: 99%

Section: Ionization Approaches With Linear Ion Trapsmentioning

confidence: 99%

mentioning

confidence: 99%

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Evolution of instrumentation for the study of gas-phase ion/ion chemistry via mass spectrometry

Xia

McLuckey

2008

J. Am. Soc. Mass Spectrom.

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“…Ion/ion proton-transfer reactions have been employed as a secondary means of manipulating both ion charge and polarity in the gas phase after the ions are formed. Previously, we reported a strategy of increasing the net charge of an ion in the gas phase by using two sequential charge inversion steps [20]. However, such studies have been conducted only with extensively modified instruments, in which two or three distinct electrospray interfaces were incorporated into the design.…”

Section: Charge Increase From a Singly Protonated Peptide To A Doublymentioning

confidence: 99%

“…One example is the increase of the absolute charge state of a polypeptide ion, which has been achieved via two sequential ion/ion protontransfer reactions involving charge inversion [20,21]. A second example includes phosphopeptide characterization via sequential proton-transfer charge inversion and electron-transfer ion/ion reactions [22], where the first ion/ion reaction inverts the polarity of phosphopeptide sprayed in negative mode and the second ion/ion reaction is used to derive structure information from the charge inverted phosphopeptide.…”

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

Liang

Han

Xia

et al. 2007

J. Am. Soc. Mass Spectrom.

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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...

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Covalent and non‐covalent binding in the ion/ion charge inversion of peptide cations with benzene‐disulfonic acid anions

2012

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Protonated angiotensin II and protonated leucine enkephalin-based peptides, which included YGGFL, YGGFLF, YGGFLH, YGGFLK, and YGGFLR, were subjected to ion/ion reactions with the doubly deprotonated reagents 4-formyl-1,3-benzenedisulfonic acid (FBDSA) and 1,3-benzenedisulfonic acid (BDSA). The major product of the ion/ion reaction is a negatively charged complex of the peptide and reagent. Following dehydration of [M+FBDSA-H]− via collisional induced dissociation (CID), angiotensin II (DRVYIHPF) showed evidence for two product populations, one in which a covalent modification has taken place and one in which an electrostatic modification has occurred (i.e., no covalent bond formation). A series of studies with model systems confirmed that strong non-covalent binding of the FBDSA reagent can occur with subsequent ion trap CID resulting in dehydration unrelated to the adduct. Ion trap CID of the dehydration product can result in cleavage of amide bonds in competition with loss of the FBDSA adduct. This scenario is most likely for electrostatically-bound complexes in which the peptide contains both an arginine residue and one or more carboxyl groups. Otherwise, loss of the reagent species from the complex, either as an anion or as a neutral species, is the dominant process for electrostatically-bound complexes. The results reported here shed new light on the nature of non-covalent interactions in gas-phase complexes of peptide ions that can be used in the rationale design of reagent ions for specific ion/ion reaction applications.

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Two Ion/Ion Charge Inversion Steps To Form a Doubly Protonated Peptide from a Singly Protonated Peptide in the Gas Phase

Cited by 55 publications

References 15 publications

Evolution of instrumentation for the study of gas-phase ion/ion chemistry via mass spectrometry

Evolution of instrumentation for the study of gas-phase ion/ion chemistry via mass spectrometry

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

Covalent and non‐covalent binding in the ion/ion charge inversion of peptide cations with benzene‐disulfonic acid anions

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