The study of protein conformation in solution via direct sampling by desorption electrospray ionization mass spectrometry

Miao, Zhixin; Wu, Shiyong; Chen, Hao

doi:10.1016/j.jasms.2010.06.003

Cited by 44 publications

(56 citation statements)

References 41 publications

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“…However, there are experiments which demonstrate that mildly denaturing conditions may not be sufficient to enable protein unfolding within the timescale of ESI. Liquid desorption electrospray ionization, or liquid DESI, developed by the Chen group, [20] can be used to introduce the analyte of interest independently from the ionization solution as shown in Figure 2a. For example, an aqueous myoglobin solution can be intersected with an ionized plume of water/methanol/ acetic acid (50/50/1).…”

Section: Timescalementioning

confidence: 99%

Reflections on Charge State Distributions, Protein Structure, and the Mystical Mechanism of Electrospray Ionization

Hamdy

Julian

2011

J. Am. Soc. Mass Spectrom.

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The connection between charge state distributions, protein structure, and mechanistic details of electrospray are discussed in relation to the emerging field of gas phase structural biology. Comparisons are drawn with the established area of enzymatic catalysis in organic solvents, which shares many similar challenges. Charge solvation emerges as a dominant force in both systems that must be dealt with to enable kinetic trapping of native structures in foreign environments. Potential methods for mediating unfavorable charge solvation effects are discussed and, ironically, do not include partial solvation by water. The importance of timescale in relation to the evolution of protein structure during the process of electrospray ionization is discussed. Finally several prospects for future endeavors are highlighted.

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Section: Timescalementioning

confidence: 99%

Reflections on Charge State Distributions, Protein Structure, and the Mystical Mechanism of Electrospray Ionization

Hamdy

Julian

2011

J. Am. Soc. Mass Spectrom.

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“…1, 5 of CTH in bulk reaction mixtures (reaction time of a few minutes) (15). Ambient ionization methods (24)(25)(26) such as desorption electrospray ionization (DESI) (27)(28)(29) provide a simpler approach to intercepting reactive species without prior sample preparation (30)(31)(32)(33)(34)(35). We recently demonstrated that DESI can intercept CTH intermediates in solution on the millisecond time scale (36).…”

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confidence: 99%

Transient Ru-methyl formate intermediates generated with bifunctional transfer hydrogenation catalysts

Perry

Brownell

Chingin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Desorption electrospray ionization (DESI) coupled to high-resolution Orbitrap mass spectrometry (MS) was used to study the reactivity of a (β-amino alcohol)(arene)RuCl transfer hydrogenation catalytic precursor in methanol (CH 3 OH). By placing ½ðp-cymeneÞ RuCl 2 2 on a surface and spraying a solution of β-amino alcohol in methanol, two unique transient intermediates having lifetimes in the submillisecond to millisecond range were detected. These intermediates were identified as Ru (II) and Ru (IV) complexes incorporating methyl formate (HCOOCH 3 ). The Ru (IV) intermediate is not observed when the DESI spray solution is sparged with Ar gas, indicating that O 2 dissolved in the solvent is necessary for oxidizing Ru (II) to Ru (IV). These proposed intermediates are supported by high-resolution and high mass accuracy measurements and by comparing experimental to calculated isotope profiles. Additionally, analyzing the bulk reaction mixture using gas chromatography-MS and nuclear magnetic resonance spectroscopy confirms the formation of HCOOCH 3 . These results represent an example that species generated from the (β-amino alcohol)(arene)RuCl (II) catalytic precursor can selectively oxidize CH 3 OH to HCOOCH 3 . This observation leads us to propose a pathway that can compete with the hydrogen transfer catalytic cycle. Although bifunctional hydrogen transfer with Ru catalysts has been well-studied, the ability of DESI to intercept intermediates formed in the first few milliseconds of a chemical reaction allowed identification of previously unrecognized intermediates and reaction pathways in this catalytic system. organometallic catalysis | reaction intermediates | ruthenium | kinetics C atalytic transfer hydrogenation (CTH) is an efficient method for the enantioselective reduction of multiple bonds (e.g., C═O and C═NR) in chemical and pharmaceutical syntheses (1-4). Typically, a hydrogen donor such as isopropanol is used as a convenient reducing agent and is oxidized to its corresponding ketone (5). As a catalytic version of the classical MeerweinPondorf-Verley reduction/Oppenaur oxidation (6-10), CTH provides a mild method for both ketone reduction and alcohol oxidation. Previous studies show that methanol (CH 3 OH) can serve as a hydrogen donor for (arene)Ru complexes ligated by β-amino alcohols (11), but the nature of the oxidized products from CH 3 OH has not been previously characterized (12). Additionally, some Pd and Ru (13, 14) catalysts can oxidize CH 3 OH to methyl formate (HCOOCH 3 ), but selective oxidation to methyl formate has not been observed previously for a transfer hydrogenation catalysis. Fig. 1 shows the mechanism proposed by Kenney, Heck, Walgrove, and Wills (15) for CTH when Fig. 1, 1 is treated with β-amino alcohol ligands in the presence of a base. Ligation of the cymene dimer Fig. 1, 1 with ligand Fig. 1, 2 generates the Ru-Cl catalyst precursor Fig. 1, 3, which undergoes dehydrohalogenation to form the Ru-amide Fig. 1, 4. An outer-sphere concerted hydrogen transfer of α-C─H to Ru and ─O─H t...

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“…The ionization occurs via the interaction of liquid sample with charged droplets generated by the DESI spray and the resulting ions are collected and analyzed by a mass spectrometer. It is useful in directly analyzing samples including large proteins/protein complexes from their native environments [16,[29][30][31][32][33][34]. Furthermore, it is possible to use liquid sample DESI-MS for studying fast reaction kinetics in submillisecond time resolution [35] or coupling with liquid chromatography (LC) [18,[36][37][38], microfluidics [26], and microextraction [39].…”

Section: Introductionmentioning

confidence: 99%

Online Investigation of Aqueous-Phase Electrochemical Reactions by Desorption Electrospray Ionization Mass Spectrometry

Lü

Liu

Helmy

et al. 2015

J. Am. Soc. Mass Spectrom.

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Abstract. Electrochemistry (EC) combined with mass spectrometry (MS) is a powerful tool for elucidation of electrochemical reaction mechanisms. However, direct online analysis of electrochemical reaction in aqueous phase was rarely explored. This paper presents the online investigation of several electrochemical reactions with biological relevance in the aqueous phase, such as nitrosothiol reduction, carbohydrate oxidation, and carbamazepine oxidation using desorption electrospray ionization mass spectrometry (DESI-MS). It was found that electroreduction of nitrosothiols [e.g., nitrosylated insulin B (13-23)] leads to free thiols by loss of NO, as confirmed by online MS analysis for the first time. The characteristic mass shift of 29 Da and the reduced intensity provide a quick way to identify nitrosylated species. Equally importantly, upon collision-induced dissociation (CID), the reduced peptide ion produces more fragment ions than its nitrosylated precursor ion (presumably the backbone fragmentation cannot compete with the facile NO loss for the precursor ion), thus facilitating peptide sequencing. In the case of saccharide oxidation, it was found that glucose undergoes electro-oxidation to produce gluconic acid at alkaline pH, but not at neutral and acidic pHs. Such a pH-dependent electrochemical behavior was also observed for disaccharides such as maltose and cellobiose. Upon electrochemical oxidation, carbamazepine was found to undergo ring contraction and amide bond cleavage, which parallels the oxidative metabolism observed for this drug in leucocytes. The mechanistic information of these redox reactions revealed by EC/DESI-MS would be of value in nitroso-proteome research and carbohydrate/drug metabolic studies.

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The study of protein conformation in solution via direct sampling by desorption electrospray ionization mass spectrometry

Cited by 44 publications

References 41 publications

Reflections on Charge State Distributions, Protein Structure, and the Mystical Mechanism of Electrospray Ionization

Reflections on Charge State Distributions, Protein Structure, and the Mystical Mechanism of Electrospray Ionization

Transient Ru-methyl formate intermediates generated with bifunctional transfer hydrogenation catalysts

Online Investigation of Aqueous-Phase Electrochemical Reactions by Desorption Electrospray Ionization Mass Spectrometry

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