On-line electrochemical–mass spectrometry study of the mechanism of oxidation of N,N-dimethyl-p-phenylenediamine in aqueous electrolytes

Модестов, А. Д.; Gun, Jenny; Savotine, Ilia; Lev, Ovadia

doi:10.1016/j.jelechem.2003.09.023

Cited by 35 publications

(23 citation statements)

References 43 publications

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“…Previous studies report that DMPD can be singly or doubly oxidized to form a cationic radical or a cationic quinoid species, respectively. 25–27 The spectral alterations of DMPD , apparent in an O 2 atmosphere in both the absence and presence of Aβ 40 , were not observed in an anaerobic condition even after 24 h incubation (Figure 3c). In addition, modulation of Aβ aggregation by DMPD was not observed under the anaerobic condition, distinguishable from that under the aerobic setting (Figure 1c, left).…”

Section: Resultsmentioning

confidence: 98%

“…The optical bands at ca. 513 and 550 nm, indicative of the formation of a cationic radical of DMPD 25–27 through an oxidative degradation route (Figure 3a,b, bottom), were not observed even after a 24 h incubation of DMPD with Aβ (Figure 3a,b, top). Upon addition of DMPD into a solution containing Aβ 40 , a red shift in the optical band of DMPD (from 295 to 305 nm) immediately occurred (Supporting Information Figure S6).…”

Section: Resultsmentioning

confidence: 99%

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A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms

et al. 2015

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Chemical reagents targeting and controlling amyloidogenic peptides have received much attention for helping identify their roles in the pathogenesis of protein-misfolding disorders. Herein, we report a novel strategy for redirecting amyloidogenic peptides into nontoxic, off-pathway aggregates, which utilizes redox properties of a small molecule (DMPD, N,N-dimethyl-p-phenylenediamine) to trigger covalent adduct formation with the peptide. In addition, for the first time, biochemical, biophysical, and molecular dynamics simulation studies have been performed to demonstrate a mechanistic understanding for such an interaction between a small molecule (DMPD) and amyloid-β (Aβ) and its subsequent anti-amyloidogenic activity, which, upon its transformation, generates ligand–peptide adducts via primary amine-dependent intramolecular cross-linking correlated with structural compaction. Furthermore, in vivo efficacy of DMPD toward amyloid pathology and cognitive impairment was evaluated employing 5xFAD mice of Alzheimer’s disease (AD). Such a small molecule (DMPD) is indicated to noticeably reduce the overall cerebral amyloid load of soluble Aβ forms and amyloid deposits as well as significantly improve cognitive defects in the AD mouse model. Overall, our in vitro and in vivo studies of DMPD toward Aβ with the first molecular-level mechanistic investigations present the feasibility of developing new, innovative approaches that employ redox-active compounds without the structural complexity as next-generation chemical tools for amyloid management.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms

et al. 2015

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“…Comparisons of the products of EC-MS and cytochrome P450 catalysed oxidation reactions as well as cleavages of peptides with EC-MS-MS were likewise described [31,32]. Other important contributions to the development of EC-ESI-MS have been made by Lev and co-workers [33][34][35].…”

Section: Introductionmentioning

confidence: 99%

The influence of the thin-layer flow cell design on the mass spectra when coupling electrochemistry to electrospray ionisation mass spectrometry

Zettersten

Lomoth

Hammarström

et al. 2006

Journal of Electroanalytical Chemistry

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“…Lev and coworkers [35] developed a radial-flow electrochemical cell coupled to an electrospray interface to study electrochemical reactions involving parallel and consecutive chemical reactions ( Figure 5.6). The electrochemical flow cell consists of two cylindrical Delrin blocks (1 and 2) separated by a 50 mm Teflon spacer (3).…”

Section: Electrochemical Cellmentioning

confidence: 99%

On‐line Monitoring Reactions by Electrospray Ionization Mass Spectrometry

Santos¹

2009

Reactive Intermediates

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In the last decade, mass spectrometry has developed at a tremendous rate. This expansion has been driven by the growing knowledge of ionization methods at atmospheric pressure (API), mainly electrospray ionization (ESI) [1], which makes the investigation of liquid solutions possible by mass spectrometry. ESI is used for ionic species in solution, and this ionization method opened up the access to the direct investigation of chemical reactions in solution via mass spectrometry. In principle, ESI make possible the detection and study not only of reaction substrates and products, but even short-lived reaction intermediates as they are present in solution, providing new insights into the mechanism of several studied reactions.ESI-MS and its tandem version ESI-MS/MS are rapidly becoming the techniques of choice for solution mechanistic studies in chemistry. Depending on the conditions set in the equipment, the ESI process can be used to transfer analyte species generally ionized in the condensed phase into the gas phase as isolated entities. An interesting method of studying intermediates using ESI is the ion fishing technique applied by Chen [2]. The suspected catalytic ionic species is fished from solution and transferred to the collision cell of the mass spectrometer, where the gas-phase catalytic reaction can be further studied by ion/molecule reactions [3].This chapter deals with applicability of on-line mechanistic investigations of catalyzed reactions through ESI-MS in the condensed phase. It is focused on the interception of intermediates in organic reactions previously proposed based on experimental evidence, and isolation of the different products, validating (or not) the empiric proposals. More detailed information about the technique can be found in some excellent reviews [4] that summarize current thinking on the various stages of the ESI process [5,6]. However, a brief description of the ESI mechanism is appropriate at his point.The electrospray process can be described with relative simplicity. A solution of the analyte is passed through a capillary held at high potential. The high voltage generates a mist of highly charged droplets, which passes through potential and pressure gradients toward the analyzer portion of the mass spectrometer. During this transition, the droplets decrease in size by evaporation of the solvent and by droplet subdivision resulting from the coulombic repulsions caused by the high charge density achieved in the shrinkage. The final result is that the ions become completely desolvated [7].The charge state of the isolated ions is assumed to closely reflect the charge state in solution (multiply charged species due to ion/molecule reactions in the interface are sometimes observed), since the transfer of ions to the gas phase is not an energetic processthe desolvation is indeed a process that effectively cools the ion [8-10]. Therefore, it can be assumed that ESI involves only the stepwise disruption of noncovalent interactions, principally the removal of molecules of solvation, an...

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On-line electrochemical–mass spectrometry study of the mechanism of oxidation of N,N-dimethyl-p-phenylenediamine in aqueous electrolytes

Cited by 35 publications

References 43 publications

A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms

A Redox-Active, Compact Molecule for Cross-Linking Amyloidogenic Peptides into Nontoxic, Off-Pathway Aggregates: In Vitro and In Vivo Efficacy and Molecular Mechanisms

The influence of the thin-layer flow cell design on the mass spectra when coupling electrochemistry to electrospray ionisation mass spectrometry

On‐line Monitoring Reactions by Electrospray Ionization Mass Spectrometry

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