Evaluating the cation binding strength and selectivity of calix[4]pyrroles: a computational and ESI-MS/MS study

Electrospray ionization (ESI) mass spectrometry (MS) has become a popular tool for monitoring ligandprotein and proteinprotein interactions. Due to the "gentle" nature of the ionization process, it is often possible to transfer weakly bound complexes into the gas phase, thus making them amenable to MS detection. One problem with this technique is the potential occurrence of fragmentation events during ESI. Also, some analytes tend to cluster together during ionization, thus forming nonspecific gas-phase assemblies that do not represent solution-phase complexes. In this work, we implemented a hydrogendeuterium exchange (HDX) approach that can reveal whether or not the free and (or) bound constituents of a complex observed in ESI-MS reflect the binding situation in solution. Proteins are subjected to ESI immediately following an isotopic labeling pulse; only ligand-free and ligand-bound protein ions that were formed directly from the corresponding solution-phase species showed different HDX levels. Using myoglobin as a model system, it is demonstrated that this approach can readily distinguish scenarios where the hemeprotein interactions were disrupted in solution from those where dissociation of the complex occurred in the gas phase. Experiments on cytochrome c strongly suggest that dimeric protein ions observed in ESI-MS reflect aggregates that were formed in solution.Key words: electrospray mass spectrometry, ligandprotein interaction, noncovalent complex, hydrogendeuterium exchange, protein folding.

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Gas-phase reactivity of protonated 2-oxazoline derivatives: mass spectrometry and computational studies

Rapid Communications in Mass Spectrometry ◽

10.1002/rcm.6182 ◽

2012 ◽

Vol 26 (9) ◽

pp. 1061-1069 ◽

Cited By ~ 5

Author(s):

Ricardo Vessecchi ◽

José Carlos Tomaz ◽

Guilherme Purcote dos Santos ◽

Alfredo R. Marques Oliveira ◽

Norberto Peporine Lopes ◽

...

Keyword(s):

Mass Spectrometry ◽

Gas Phase ◽

Computational Studies ◽

Oxazoline Derivatives

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Photodegradation of Riboflavin under Alkaline Conditions: What can Gas-Phase Photolysis Tell Us About What Happens in Solution?

10.20944/preprints202108.0307.v1 ◽

2021 ◽

Author(s):

Natalie G.K. Wong ◽

Chris Rhodes ◽

Caroline E.H. Dessent

Keyword(s):

Mass Spectrometry ◽

Gas Phase ◽

Direct Method ◽

Photochemical Reactions ◽

Solution Phase ◽

Ionization Mass ◽

Phase Reaction ◽

Esi Ms ◽

Alkaline Conditions ◽

On Line

The application of electrospray ionization mass spectrometry (ESI-MS) as a direct method for detecting reactive intermediates is a technique of developing importance in the routine monitoring of solution-phase reaction pathways. Here, we utilize a novel on-line photolysis ESI-MS approach to detect the photoproducts of riboflavin in aqueous solution under mildly alkaline conditions. Riboflavin is a constituent of many food products, so its breakdown processes are of wide interest. Our on-line photolysis setup allows for solution-phase photolysis to occur within a syringe using UVA LEDs, immediately prior to being introduced into the mass spectrometer via ESI. Gas-phase photofragmentation studies via laser-interfaced mass spectrometry of deprotonated riboflavin, [RFH], the dominant solution-phase species under the conditions of our study, are presented alongside the solution-phase photolysis. The results obtained illustrate the extent to which gas-phase photolysis methods can inform our understanding of the corresponding solution-phase photochemistry. We determine that the solution-phase photofragmentation observed for [RFH] closely mirrors the gas-phase photochemistry, with the m/z 241 ion being the only major condensed-phase photoproduct. Further gas-phase photoproducts are observed at m/z 255, 212, and 145. The value of exploring both the gas- and solution-phase photochemistry to characterize photochemical reactions is discussed.

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Evaluation of the supramolecular interaction of Congo red with cucurbiturils using mass spectrometry and spectroscopic methods

New Journal of Chemistry ◽

10.1039/c9nj05706d ◽

2020 ◽

Vol 44 (6) ◽

pp. 2587-2596 ◽

Cited By ~ 1

Author(s):

Ana L. Costa ◽

Ana C. Gomes ◽

André D. Lopes ◽

José P. Da Silva ◽

Martyn Pillinger ◽

...

Keyword(s):

Mass Spectrometry ◽

Aqueous Solutions ◽

Gas Phase ◽

Outer Surface ◽

Congo Red ◽

Spectroscopic Methods ◽

Supramolecular Interaction ◽

Esi Ms

Cucurbit[n]urils decolourise aqueous solutions of Congo red by forming outer-surface adducts, which are also detected in gas-phase ESI-MS studies.

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A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.10.211 ◽

2014 ◽

Vol 10 ◽

pp. 2027-2037 ◽

Cited By ~ 7

Author(s):

J Alexander Willms ◽

Rita Beel ◽

Martin L Schmidt ◽

Christian Mundt ◽

Marianne Engeser

Keyword(s):

Mass Spectrometry ◽

Gas Phase ◽

Electrospray Mass Spectrometry ◽

Temporal Evolution ◽

Mechanistic Studies ◽

Catalytic Center ◽

Enamine Catalysis ◽

Esi Mass Spectrometry ◽

Catalyzed Reactions ◽

Gas Phase Fragmentation

A new 4-hydroxy-L-proline derivative with a charged 1-ethylpyridinium-4-phenoxy substituent has been synthesized with the aim of facilitating mechanistic studies of proline-catalyzed reactions by ESI mass spectrometry. The charged residue ensures a strongly enhanced ESI response compared to neutral unmodified proline. The connection by a rigid linker fixes the position of the charge tag far away from the catalytic center in order to avoid unwanted interactions. The use of a charged catalyst leads to significantly enhanced ESI signal abundances for every catalyst-derived species which are the ones of highest interest present in a reacting solution. The new charged proline catalyst has been tested in the direct asymmetric inverse aldol reaction between aldehydes and diethyl ketomalonate. Two intermediates in accordance with the List–Houk mechanism for enamine catalysis have been detected and characterized by gas-phase fragmentation. In addition, their temporal evolution has been followed using a microreactor continuous-flow technique.

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The effect of gas-phase reactions on the quantitation of cyclic hydrazone libraries by electrospray ionization (ESI) mass spectrometry

Organic & Biomolecular Chemistry ◽

10.1039/b808490d ◽

2008 ◽

Vol 6 (19) ◽

pp. 3597 ◽

Cited By ~ 12

Author(s):

Holly Schiltz ◽

Mee-Kyung Chung ◽

Stephen J. Lee ◽

Michel R. Gagné

Keyword(s):

Mass Spectrometry ◽

Electrospray Ionization ◽

Gas Phase ◽

Gas Phase Reactions ◽

Esi Mass Spectrometry

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DNA and RNA Telomeric G-Quadruplexes: What Topology Features Can be Inferred from Ion Mobility Mass Spectrometry?

10.26434/chemrxiv.8246975 ◽

2019 ◽

Author(s):

Valentina D’Atri ◽

Valerie Gabelica

Keyword(s):

Mass Spectrometry ◽

Gas Phase ◽

Ion Mobility Spectrometry ◽

Ion Mobility ◽

Native Mass Spectrometry ◽

Cation Binding ◽

Telomeric Dna ◽

Dna And Rna ◽

G Quadruplex ◽

Multiple Structures

Maintenance of the telomeres is key to chromosome integrity and cell proliferation. The G-quadruplex structures formed by telomeric DNA and RNA (TTAGGG and UUAGGG repeats, respectively) are key to this process. However, because these sequences are particularly polymorphic, solving high-resolution structures is not always possible, and there is a need for new methodologies to characterize the multiple structures coexisting in solution. In this context, we evaluated whether ion mobility spectrometry coupled to native mass spectrometry could help separate and assign the G-quadruplex topologies. We explored the circular dichroism spectra, multimer formation, cation binding, and ion mobility spectra of several 4-repeat and 8-repeat telomeric DNA and RNA sequences, both in NH4+ and in K+. In 1 mM K+ and 100 mM trimethylammonium acetate, all RNAs fold intramolecularly (no multimer). In 8-repeat sequences, the subunits are not independent: in DNA the first subunit disfavors the folding of the second one, whereas in RNA the two subunits fold cooperatively via cation-mediated stacking. Ion mobility spectrometry shows that gas-phase structures keep a memory of the solution ones, but not identical. At the native charge states, the loops can rearrange in a variety of ways (unless they are constrained by pre-formed hydrogen bonds), thereby wrapping the core and masking the strand arrangements. Our study highlights that, to progress towards structural assignment from IM-MS experiments, deeper understanding of the solution-to-gas-phase rearrangement mechanisms is warranted.

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DNA and RNA Telomeric G-Quadruplexes: What Topology Features Can be Inferred from Ion Mobility Mass Spectrometry?

10.26434/chemrxiv.8246975.v1 ◽

2019 ◽

Author(s):

Valentina D’Atri ◽

Valerie Gabelica

Keyword(s):

Mass Spectrometry ◽

Gas Phase ◽

Ion Mobility Spectrometry ◽

Ion Mobility ◽

Native Mass Spectrometry ◽

Cation Binding ◽

Telomeric Dna ◽

Dna And Rna ◽

G Quadruplex ◽

Multiple Structures

Maintenance of the telomeres is key to chromosome integrity and cell proliferation. The G-quadruplex structures formed by telomeric DNA and RNA (TTAGGG and UUAGGG repeats, respectively) are key to this process. However, because these sequences are particularly polymorphic, solving high-resolution structures is not always possible, and there is a need for new methodologies to characterize the multiple structures coexisting in solution. In this context, we evaluated whether ion mobility spectrometry coupled to native mass spectrometry could help separate and assign the G-quadruplex topologies. We explored the circular dichroism spectra, multimer formation, cation binding, and ion mobility spectra of several 4-repeat and 8-repeat telomeric DNA and RNA sequences, both in NH4+ and in K+. In 1 mM K+ and 100 mM trimethylammonium acetate, all RNAs fold intramolecularly (no multimer). In 8-repeat sequences, the subunits are not independent: in DNA the first subunit disfavors the folding of the second one, whereas in RNA the two subunits fold cooperatively via cation-mediated stacking. Ion mobility spectrometry shows that gas-phase structures keep a memory of the solution ones, but not identical. At the native charge states, the loops can rearrange in a variety of ways (unless they are constrained by pre-formed hydrogen bonds), thereby wrapping the core and masking the strand arrangements. Our study highlights that, to progress towards structural assignment from IM-MS experiments, deeper understanding of the solution-to-gas-phase rearrangement mechanisms is warranted.

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