The Competition of Charge Remote and Charge Directed Fragmentation Mechanisms in Quaternary Ammonium Salt Derivatized Peptides—An Isotopic Exchange Study

Derivatization of peptides as quaternary ammonium salts (QAS) is a promising method for sensitive detection by electrospray ionization tandem mass spectrometry (Cydzik et al. J. Pept. Sci. 2011, 17, 445–453). The peptides derivatized by QAS at their N-termini undergo fragmentation according to the two competing mechanisms – charge remote (ChR) and charge directed (ChD). The absence of mobile proton in the quaternary salt ion results in ChR dissociation of a peptide bond. However, Hofmann elimination of quaternary salt creates an ion with one mobile proton leading to the ChD fragmentation. The experiments on the quaternary ammonium salts with deuterated N-alkyl groups or amide NH bonds revealed that QAS derivatized peptides dissociate according to the mixed ChR-ChD mechanism. The isotopic labeling allows differentiation of fragments formed according to ChR and ChD mechanisms.     

Fragmentation of β-hydroxy hydroperoxides

A β-hydroxy hydroperoxide was obtained through base-catalyzed disproportionation of a hydroperoxy endoperoxide available by singlet oxygenation of cyclohepta-1,4-diene. Vitamins E and C induce fragmentation of this β-hydroxy hydroperoxide generating aldehydes, especially in the presence of redox active metal ions such as those present in vivo, e.g., under conditions of "iron overload". This chemistry may contribute to the oxidative cleavage of polyunsaturated fatty acyls that produces similar aldehydes, which damage proteins and DNA through covalent adduction resulting in "oxidative injury".     

Fragmentation of <Emphasis Type="Italic">α</Emphasis>-radical cations of arginine-containing peptides

Fragmentation pathways of peptide radical cations, M^+·, with well-defined initial location of the radical site were explored using collision-induced dissociation (CID) experiments. Peptide radical cations were produced by gas-phase fragmentation of Co^III(salen)-peptide complexes [salen=N,N′-ethylenebis (salicylideneiminato)]. Subsequent hydrogen abstraction from the β-carbon of the side-chain followed by C_α-C_β bond cleavage results in the loss of a neutral side chain and formation of an α-radical cation with the radical site localized on the α-carbon of the backbone. Similar CID spectra dominated by radical-driven dissociation products were obtained for a number of arginine-containing α-radicals, suggesting that for these systems radical migration precedes fragmentation. In contrast, proton-driven fragmentation dominates CID spectra of α-radicals produced via the loss of the arginine side chain. Radical-driven fragmentation of large M^+· peptide radical cations is dominated by side-chain losses, formation of even-electron a-ions and odd-electron x-ions resulting from C_α-C bond cleavages, formation of odd-electron z-ions, and loss of the N-terminal residue. In contrast, charge-driven fragmentation produces even-electron y-ions and odd-electron b-ions.     

Why Are Proteins Charged? Networks of Charge–Charge Interactions in Proteins Measured by Charge Ladders and Capillary Electrophoresis

Almost all proteins contain charged amino acids. While the function in catalysis or binding of individual charges in the active site can often be identified, it is less clear how to assign function to charges beyond this region. Are they necessary for solubility? For reasons other than solubility? Can manipulating these charges change the properties of proteins? A combination of capillary electrophoresis (CE) and protein charge ladders makes it possible to study the roles of charged residues on the surface of proteins outside the active site. This method involves chemical modification of those residues to generate a large number of derivatives of the protein that differ in charge. CE separates those derivatives into groups with the same number of modified charged groups. By studying the influence of charge on the properties of proteins using charge ladders, it is possible to estimate the net charge and hydrodynamic radius and to infer the role of charged residues in ligand binding and protein folding.     

Is the Addition‐Fragmentation Step of the RAFT Polymerisation Process Chain Length Dependent?

Summary: The chain length dependence of the addition‐fragmentation equilibrium constant (K) for cumyl dithiobenzoate (CDB) mediated polymerisation of styrene has been studied via high level ab initio molecular orbital calculations. The results indicate that chain length and penultimate unit effects are extremely important during the early stages of the polymerisation process. In the case of the attacking radical (i.e., R• in: R• + SC(Z)SR′ → RSC•(Z)SR′), the equilibrium constant varies by over three orders of magnitude on extending R• from the styryl unimer to the trimer species and actually increases with chain length, further confirming that K is high in this system. When the reactions of the cumyl leaving group and cyanoisopropyl initiating species, which are also present in CDB‐mediated polymerisation of styrene in the presence of the initiator 2,2′‐azoisobutyronitrile, are also included, the variation in K extends over five orders of magnitude. Although less significant, the influence of the R′ group should also be taken into account in a complete kinetic model of the RAFT process. However, for most practical purposes, its chain length effects beyond the unimer stage may be ignored. These results indicate that current simplified models of the RAFT process, which typically ignore all chain length effects in the R and R′ positions, and all substituent effects in the R′ position, may be inadequate, particularly in modelling the initial stages of the process.

     

Charge attachment–induced transport: toward new paradigms in solid state electrochemistry

Modern applications in solid state electrochemistry, e.g. in the field of energy storage and conversion, involve the transport of charge carriers through surfaces or interfaces as a key aspect. Many of the electrochemical concepts in fact originate from the field of liquid state electrochemistry. The transfer of concepts from the liquid to the solid state causes some problem which are addressed in this review. Topics covered include (i) electrode potentials and half-cell potentials, (ii) charge carrier blocking and dielectric breakdown, and (iii) activities versus particle densities. Many of these topics can be addressed by the charge attachment–induced transport technique developed in the authors group. The discussion involves modifying some of the paradigms we became acquainted to in the liquid state.     

Fragmentation Reactions of b<Subscript>5</Subscript> and a<Subscript>5</Subscript> Ions Containing Proline—The Structures of a<Subscript>5</Subscript> Ions

A detailed study has been made of the b₅ and a₅ ions derived from the amides H-Ala-Ala-Ala-Ala-Pro-NH₂, H-Ala-Ala-Ala-Pro-Ala-NH₂, and H-Ala-Ala-Pro-Ala-Ala-NH₂. From quasi-MS³ experiments it is shown that the product ion mass spectra of the three b₅ ions are essentially identical, indicating macrocyclization/reopening to produce a common mixture of intermediates prior to fragmentation. This is in agreement with numerous recent studies of sequence scrambling in b ions. By contrast, the product ion mass spectra for the a₅ ions show substantial differences, indicating significant differences in the mixture of structures undergoing fragmentation for these three species. The results are interpreted in terms of a mixture of classical substituted iminium ions as well as protonated C-terminal amides formed by cyclization/rearrangement as reported recently for a₄ ions (Bythell, Maître , Paizs, J . Am. Chem. Soc. 2010, 132, 14761–14779). Novel fragment ions observed upon fragmentation of the a₅ ions are protonated H-Pro-NH₂ and H-Pro-Ala-NH₂ which arise by fragmentation of the amides. The observation of these products provides strong experimental evidence for the cyclization/rearrangement reaction to form amides and shows that it also applies to a₅ ions.     

Carbanion or Amide? First Charge Density Study of Parent 2‐Picolyllithium

The negative charge originating from deprotonation of the methyl group is distributed over the 2‐picolyl ring. Bonding properties derived from the electron density distribution support the enamide character of picolyllithium (PicLi; the picture shows the deformation density of [2‐PicLi?PicH]₂), but electrophilic attack occurs at the deprotonated C atom. This reactivity is rationalized by the electrostatic potential, which guides electrophiles towards the nucleophilic C atom.

     

Gas-Phase Fragmentation of [M + nH + OH]<Superscript>n•+</Superscript> Ions Formed from Peptides Containing Intra-Molecular Disulfide Bonds

In this study, we systematically investigated gas-phase fragmentation behavior of [M + nH + OH]^n•+ ions formed from peptides containing intra-molecular disulfide bond. Backbone fragmentation and radical initiated neutral losses were observed as the two competing processes upon low energy collision-induced dissociation (CID). Their relative contribution was found to be affected by the charge state (n) of [M + nH + OH]^n•+ ions and the means for activation, i.e., beam-type CID or ion trap CID. Radical initiated neutral losses were promoted in ion-trap CID and for lower charge states where mobile protons were limited. Beam-type CID and dissociation of higher charge states of [M + nH + OH]^n•+ ions generally gave abundant backbone fragmentation, which was highly desirable for characterizing peptides containing disulfide bonds. The amount of sequence information obtained from CID of [M + nH + OH]^n•+ ions was compared with that from CID of disulfide bond reduced peptides. For the 11 peptides studied herein, similar extent of sequence information was obtained from these two methods.     

Photo-induced Charge Separation of p-Tricyanovinyl-N,N-Dialkylanilines

In this paper,p-tricyanovinyl-N,N-dialkylanilines were synthesized as model compounds and through their spectroscopic behavior,the photo-induced electron transfer,charge separation were discussed and the aggregation in DMSO-H_2O system was investigated.     

Charge Transport in BaCe<Subscript>0.85</Subscript>R<Subscript>0.15</Subscript>O<Subscript>3 − δ</Subscript> (R = Sm,Pr, Tb) in Oxidizing and Reducing Environment

Overall conductance (in moist and dry air at partial water vapor pressures of 2.34 and 40 Pa, below 970° C) and transport numbers for ions and protons in ceramics BaCe_0.85R_0.15O_{3 − δ} doped by cations with constant (R = Sm) and variable (R = Pr, Tb) oxidation degrees and in BaCeO₃ are measured. Partial conductances (by ions, protons, oxygen ions, holes) are determined in moist air at partial oxygen pressures of 10⁵–10⁻¹³ Pa at 900°C. Various models for the hydrogen incorporation in the oxides under study are discussed.__________Translated from Elektrokhimiya, Vol. 41, No. 6, 2005, pp. 748–754.Original Russian Text Copyright © 2005 by Sharova, Gorelov, Balakireva.