References of "Morsa, Denis"
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See detailSolvent Adducts in Ion Mobility Spectrometry: Toward an Alternative Reaction Probe for Thermometer Ions
Morsa, Denis ULiege; Hanozin, Emeline ULiege; Eppe, Gauthier ULiege et al

in Journal of the American Society for Mass Spectrometry (2020)

The fragmentation of benzylpyridinium "thermometer" ions is widely used to quantify the energetics of ions studied by mass spectrometry and other hyphenated techniques such as ion mobility. The reaction ... [more ▼]

The fragmentation of benzylpyridinium "thermometer" ions is widely used to quantify the energetics of ions studied by mass spectrometry and other hyphenated techniques such as ion mobility. The reaction pathway leads to a benzylium cation with the release of a neutral pyridine. Using trapped ion mobility spectrometry, we noticed that the addition of acetonitrile, present in the electrosprayed solvent mixture, could occur on some electrophilic benzylium cations. This process results in the formation of adducts and in the appearance of a supplementary mobility peak. We here demonstrate that the addition takes place both in the electrospray source and inside the mobility analyzer, thereby evidencing possible outflow of solvent vapors downstream the instrument. By further characterizing the initial kinetics and the resulting equilibrium linked with the addition reaction, we presently discuss these as alternative probes to calibrate ion temperature in the framework of ion mobility. [less ▲]

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See detailEffective Temperature and Structural Rearrangement in Trapped Ion Mobility Spectrometry
Morsa, Denis ULiege; Hanozin, Emeline ULiege; Eppe, Gauthier ULiege et al

in Analytical Chemistry (2020)

Modern ion mobility instrumentations are typically operated above the low field limit, which may activate the ions and cause structural rearrangement or fragmentation during the analysis. Here, we ... [more ▼]

Modern ion mobility instrumentations are typically operated above the low field limit, which may activate the ions and cause structural rearrangement or fragmentation during the analysis. Here, we quantitatively assessed the internal heating experienced by ions during trapped ion mobility spectrometry (TIMS) experiments. To this end, the fragmentation yields of fragile benzylpyridinium “thermometer” ions were monitored during both the accumulation and analysis steps inside the TIMS tunnel. The corresponding fragmentation rate constants were translated into a vibrational effective temperature Teff,vib. Our results demonstrate significant fragmentation upstream and inside the TIMS tunnel that corresponds to Teff,vib ≈ 510 K during both the accumulation and analysis steps. Broadening our scope to cytochrome c and lysozyme, we showed that although compact “native” folds can be preserved, the collision cross section distributions are highly sensitive to the transmission voltages and the analysis timescale. Our results are discussed with regard to Teff,vib data previously acquired on traveling-wave (TWIMS) ion mobility in the context of native mass spectrometry and conformational landscape exploration. [less ▲]

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See detailTwo-Parameter Power Formalism for Structural Screening of Ion Mobility Trends: Applied Study on Artificial Molecular Switches
Hanozin, Emeline ULiege; Morsa, Denis ULiege; De Pauw, Edwin ULiege

in Journal of Physical Chemistry. A (2019), 123

Recent literature provides increasing samples of structural studies relying on ion mobility coupled to mass spectrometry in view of characterizing gas-phase conformation and energetics properties of ... [more ▼]

Recent literature provides increasing samples of structural studies relying on ion mobility coupled to mass spectrometry in view of characterizing gas-phase conformation and energetics properties of biomolecular ions. A typical framework consists in experimentally monitoring the collisional cross sections for various experimental conditions and using them as references to select appropriate candidate structures issued from theoretical modeling. Although it has proved successful for structural assignment, this process is resource costly and lengthy, namely due to intricacies in the selection of appropriate input geometries. In the present work, we propose simplified methodologies dedicated to the systematic screening of ion mobility data acquired on systems built from repetitive subunits and detail their application to challenging artificial molecular switch systems. Capitalizing on coarse-grained design, we first demonstrate how the assimilation of subunits into adequately assembled building-blocks can be used for fast assignments of a system topology. Further focusing on topology-specific differential ion mobility trends, we show that the building-block assemblies can be fused into single fully convex solid figure models, i.e., sphere and cylinder, whose projected areas follow a two-parameter power formalism A × nB. We show that the fitting parameters A and B were assigned as structural descriptors respectively associated with the dimensions of each constitutive subunit, i.e., size parameter, and with their assembled tridimensional arrangement, i.e., shape parameter. The present work provides a ready-to-use method for the screening of IM-MS data sets that is expected to facilitate the eventual design of input structures whenever advanced modeling calculations are required. [less ▲]

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See detailMulti-Enzymatic Limited Digestion: The Next-Generation Sequencing for Proteomics?
Morsa, Denis ULiege; Baiwir, Dominique ULiege; La Rocca, Raphaël ULiege et al

in Journal of proteome research (2019)

Over the past 40 years, proteomics, generically defined as the field dedicated to the identification and analysis of proteins, has tremendously gained in popularity and potency through advancements in ... [more ▼]

Over the past 40 years, proteomics, generically defined as the field dedicated to the identification and analysis of proteins, has tremendously gained in popularity and potency through advancements in genome sequencing, separative techniques, mass spectrometry, and bioinformatics algorithms. As a consequence, its scope of application has gradually enlarged and diversified to meet specialized topical biomedical subjects. Although the tryptic bottom-up approach is widely regarded as the gold standard for rapid screening of complex samples, its application for precise and confident mapping of protein modifications is often hindered due to partial sequence coverage, poor redundancy in indicative peptides, and lack of method flexibility. We here show how the synergic and time-limited action of a properly diluted mix of multiple enzymes can be exploited in a versatile yet straightforward protocol to alleviate present-day drawbacks. Merging bottom-up and middle-down ideologies, our results highlight broad assemblies of overlapping peptides that enable refined and reliable characterizations of proteins, including variant identification, and their carried modifications, including post-translational modifications, truncations, and cleavages. Beyond this boost in performance, our methodology also offers efficient de novo sequencing capabilities, in view of which we here present a dedicated custom assembly algorithm. [less ▲]

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See detailProteomics highlights common and distinct pathophysiological processes associated with ileal and colonic ulcers in Crohn's disease.
Pierre, Nicolas ULiege; Salee, Catherine ULiege; MASSOT, Charlotte ULiege et al

in Journal of Crohn's & colitis (2019)

BACKGROUND AND AIMS: Based on genetics and natural history, Crohn's disease can be separated in two entities, an ileal and a colonic disease. Protein based-approaches are needed to elucidate whether such ... [more ▼]

BACKGROUND AND AIMS: Based on genetics and natural history, Crohn's disease can be separated in two entities, an ileal and a colonic disease. Protein based-approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes. METHODS: The proteome of ulcer edge was compared to the one of paired control tissue (n=32 biopsies) by differential proteomics in the ileum and the colon of Crohn's disease patients (n=16). The results were analysed though a hypothesis-driven (based on literature) and a hypothesis-free approach (pathway enrichment analysis). To confirm one of the key pathway highlighted by proteomics, two proteins were also studied by immunochemistry in tissue biopsies. RESULTS: In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edge differed by a distinct distribution of proteins of epithelial-mesenchymal transition, neutrophil degranulation and ribosome. Ileal and colonic ulcer edge were similarly characterised by an increase of the proteins implicated in the pathway of protein processing in endoplasmic reticulum and a decrease of mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edge. CONCLUSION: This study provides protein-based evidences showing partly distinct pathophysiological processes associated to ileal and colonic ulcer edge in Crohn's disease patients. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics. [less ▲]

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See detailCovalent Cross-Linking as an Enabler for Structural Mass Spectrometry
Hanozin, Emeline ULiege; Grifnée, Elodie ULiege; Gattuso, Hugo ULiege et al

in Analytical Chemistry (2019)

Studies referring to the structural elucidation of intact biomolecular systems using mass spectrometry techniques have been gradually flourishing in the post-2000s literature topics. As part of native ... [more ▼]

Studies referring to the structural elucidation of intact biomolecular systems using mass spectrometry techniques have been gradually flourishing in the post-2000s literature topics. As part of native mass spectrometry, this domain capitalizes on the kinetic trapping of physiological folds in view of probing solution-like conformational properties of isolated molecules or complexes after their electrospray transfer to the gas phase. Despite its documented efficiency for a wide array of analytes, this approach is expected to be pushed to its limits when considering highly dynamic systems or when dealing with non-ideal operating conditions. To circumvent these limitations, we challenge the adequacy of an original strategy based on cross-linkers to improve the gas-phase stability of isolated proteins and ensure the preservation of folded conformations when measuring with strong transmission voltages, by spraying from denaturing solvents or trapping for extended periods of time. Tested on cytochrome c, myoglobin and β-lactoglobulin cross-linked using BS3, we validated the process as a structurally non-intrusive in solution using far-ultraviolet circular dichroism and unraveled the preservation of folded conformations showing better resilience to denaturation on cross-linked species using ion mobility. The resulting collision cross sections were found in agreement with the native fold, and a preservation of the proteins’ secondary and tertiary structures was evidenced using molecular dynamics simulations. Our results provide new insights concerning the fate of electro-sprayed cross-linked conformers in the gas phase, while constituting promising evidence for the validation of this technique as part of tomorrow’s structural mass spectrometry workflows. [less ▲]

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See detailBenchmarking IM-MS gas-phase data based on cross-linking strategies
Hanozin, Emeline ULiege; Grifnée, Elodie ULiege; Gattuso, Hugo ULiege et al

Conference (2019)

Since the apparition of conservative soft-ionization sources in the late 80s, i.e. electrospray (ESI) and matrix-assisted laser desorption-ionization, mass spectrometry (MS) has been extensively used to ... [more ▼]

Since the apparition of conservative soft-ionization sources in the late 80s, i.e. electrospray (ESI) and matrix-assisted laser desorption-ionization, mass spectrometry (MS) has been extensively used to identify, quantify and characterize wide types of biomolecules. Especially, ESI sources make feasible the transfer of intact biomolecules and macromolecular complexes in the mass spectrometer, opening the so-called field of “native” MS. However, major questioning and inherent skepticism yet surround the native MS field concerning the ability to preserve non-bonded biological interactions during and after the molecular transfer from the physiological aqueous media to the gas-phase. Indeed, the introduction of biological structures into the gas-phase may eventually result in a reshape of their tridimensional fold, therefore leading to a misinterpretation of further derived structural data. In an effort to circumvent gas-phase unfolding scenarios, we here suggest a structural strategy relying on intra-molecular covalent cross-linkers acting as molecular scaffolds. We focused on small 10 kDa to 20 kDa proteins, such as cytochrome c, myoglobin and β-lactoglobulin, which are yet often used as model systems to gauge wide range of structural, kinetic and thermodynamics methodologies. We studied the products of “type 0” and “type 1” cross-linking reactions achieved using bissulfosuccinimidyl suberate (BS3) as a linker reagent and compared them with their non-linked counter-parts regarding their respective structural properties. The model systems were structurally investigated both in solution, through circular dichroism and thermal denaturation measurements, and in the gas-phase following ESI injection, through IM-MS and collision induced unfolding (CIU) measurements. The gas-phase data were acquired from different solvent conditions and compared with “native-compliant” benchmarks furnished by NMR spectroscopy. In general, the content in secondary structures within the proteins was found barely unaffected by the presence of the linkers when operating in physiological solution, therefore witnessing a preservation of the native fold upon linking reaction. However, after ionization and transfer into the gas-phase, we monitored significant reshapes in the conformational landscapes materialized through a shift of the collision cross-sections distribution towards lower values when linkers are present. The magnitude of the compaction effect is directly dependent on the protein charge and linker content. Altogether, the comprehension of the fate of electro-sprayed cross-linked conformers in the gas-phase and their respective correlation with the physiological fold achieved in solution constitute major steps in the validation of this technique as part of native MS workflows. [less ▲]

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See detailCan we correlate ion mobility mass spectrometry data with native solution structures? A crosslinking approach
Hanozin, Emeline ULiege; Grifnée, Elodie ULiege; Morsa, Denis ULiege et al

Poster (2018, June)

Introduction: The structural characterization of biomolecules is of prime importance in the understanding of biological processes at the molecular level. In this context, the development of soft ... [more ▼]

Introduction: The structural characterization of biomolecules is of prime importance in the understanding of biological processes at the molecular level. In this context, the development of soft ionization techniques, namely electrospray ionization, and the advent of ion mobility (IM) separation tools open new perspectives for the analysis of large intact molecular ions by mass spectrometry (MS). Previous (IM-)MS experiments emphasized that the solution phase structures may be (partially) preserved in the gas phase under soft ionization conditions. However, several factors (e.g. coulombic interactions, accelerating voltages) have an influence on the conformation of biomolecular ions in the gas phase and should be carefully considered. Consequently, some fundamental questions remain elusive: “Can we correlate ion mobility mass spectrometry data to native solution structures?” Methods: To bring innovative answers to these longtime debated questions, we here propose an early stage study targeting constrained “native-like” conformations in the gas phase. To this end, we capitalize on a crosslinking approach to establish chemical links between lysine residues located in close spatial proximity within the protein. The so-created covalent network is here used as a scaffold to prevent the collapsing and unfolding of biomolecular ions once desolvated in the gas phase. These “frozen” native solution conformations are then interrogated using ion mobility as implemented on the commercial SYNAPT G2 HDMS spectrometer. Preliminary data: Practically, we used cytochrome c as a model system that we crosslinked with BS3 linkers. Using ion mobility, we monitored the evolution of the collision cross section (CCS) quantity, a rotationally averaged 2D projection of the ion conformation, for each charge state as function of the number of covalent intramolecular linkers. These data were readily compared with those obtained in similar conditions for the non-crosslinked cytochrome c as well as with a benchmark corresponding to the native solution conformations as resolved by NMR spectroscopy. Our results highlight that the crosslinked cytochrome c adopts more compact conformations in the gas phase, closer to values monitored for the native solution conformation, compared to its non-crosslinked homologue. In addition, we found that a critical number of intramolecular linkers were required to prevent structural unfolding from Coulomb repulsions. Novel aspect: Bring innovative answers to the longtime debated native MS questions based on an alternative application of intramolecular covalent linkers. [less ▲]

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See detailGel-free proteomics
Baiwir, Dominique ULiege; Nanni, P.; Müller, S. et al

in Proteomics in Domestic Animals: from Farm to Systems Biology (2018)

Mass spectrometry (MS)-based proteomics is nowadays considered as a mainstream analytical tool for life sciences. This success is mainly to be attributed to the tremendous improvements in the core ... [more ▼]

Mass spectrometry (MS)-based proteomics is nowadays considered as a mainstream analytical tool for life sciences. This success is mainly to be attributed to the tremendous improvements in the core technology of mass spectrometry coupled with recent developments in bioinformatics and separation sciences. The level of information that is henceforth accessible through MS techniques is broad and encompasses the protein sequence as well as its quantity, modification(s), structure, and implication in macromolecular assemblies. The current chapter focuses on the existing gel-free MS-based quantitative approaches that are applicable in the field of animal sciences and summarizes their principal features together with their respective advantages and drawbacks. In this context, we will discuss both the label-free and label-based relative quantitation strategies as well as the existing alternatives for absolute quantitation. The specific case of posttranslational modifications, whose extensive characterization is becoming a crucial topic in MS-based proteome studies, is next addressed under the quantitative scope of phosphorylation and glycosylation. Lastly, other promising nonmainstream techniques are presented, emphasizing their potent use to solve major proteomics challenges of tomorrow. © Springer International Publishing AG 2018. All rights reserved. [less ▲]

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See detailPredicting Ion Mobility-Mass Spectrometry Trends of Polymers using the Concept of Apparent Densities
Haler, Jean ULiege; Morsa, Denis ULiege; Lecomte, Philippe ULiege et al

in Methods (2018), 144

Ion Mobility (IM) coupled to Mass Spectrometry (MS) has been used for several decades, bringing a fast separation dimension to the MS detection. IM-MS is a convenient tool for structural elucidation. The ... [more ▼]

Ion Mobility (IM) coupled to Mass Spectrometry (MS) has been used for several decades, bringing a fast separation dimension to the MS detection. IM-MS is a convenient tool for structural elucidation. The fold- ing of macromolecules is often assessed with the support of computational chemistry. However, this strat- egy is strongly dependent on computational initial guesses. Here, we propose the analysis of the Collision Cross-Section (CCS) trends of synthetic homopolymers based on a fitting method which does not rely on computational chemistry a prioris of the three-dimensional structures. The CCS trends were evaluated as a function of the polymer chain length and the charge state. This method is also applicable to mobility trends. It leads to two parameters containing all information available through IM(-MS) measurements. One parameter can be interpreted as an apparent density. The second parameter is related to the shape of the ions and leads us to introduce the concept of trends with constant apparent density. Based on the two fitting parameters, a method for IM trend predictions is elaborated. Experimental deviations from the predictions facilitate detect- ing structural rearrangements and three-dimensional structure differences of the cationized polymer ions. This leads for instance to an easy identification and prediction of the presence of different polymer topologies in complex polymer mixtures. The classification of predicted trends could as well allow for software-assisted data processing. Finally, we suggest the link between the CCS trends of homopolymers and those obtained from (monodisperse) biomolecules to interpret potential folding differences during IM-MS studies. [less ▲]

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See detailWhere Ion Mobility and Molecular Dynamics Meet to Unravel the (Un)Folding Mechanisms of an Oligorotaxane Molecular Switch
Hanozin, Emeline ULiege; Mignolet, Benoît ULiege; Morsa, Denis ULiege et al

in ACS Nano (2017), 11(10), 10253-10263

At the interface between foldamers and mechanically interlocked molecules, oligorotaxanes exhibit a spring-like folded secondary structure with remarkable mechanical and physicochemical properties. Among ... [more ▼]

At the interface between foldamers and mechanically interlocked molecules, oligorotaxanes exhibit a spring-like folded secondary structure with remarkable mechanical and physicochemical properties. Among these properties, the ability of oligorotaxanes to act as molecular switches through controlled modulations of their spatial extension over (un)folding dynamics is of particular interest. The present study aims to assess and further characterize this remarkable feature in the gas phase using mass spectrometry tools. In this context, we focused on the [4]5NPR+12 oligorotaxane molecule complexed with PF6 - counterion and probed its co-conformational states as a function of the in-source-generated charge states. Data were interpreted in light of electronic secondary structure computations at the PM6 and DFT levels. Our results highlight two major co-conformational groups associated either with folded compact structures, notably stabilized by intramolecular π-π interactions and predominant for low charge states or with fully stretched structures resulting from significant Coulombic repulsions at high charge states. Between, the oligorotaxane adopts intermediate folded co-conformations, suggesting a stepwise unfolding pathway under increasing repulsive Coulombic constraints. The reversibility of this superstructural transition was next interrogated under electron-driven (nondissociative electron transfer) and heat-driven (collision-induced unfolding) activation stimuli. The outcomes support the feasibility to either unfold or (partially) refold the oligorotaxane foldamer on purpose in the gas phase. Our results show that the balance between the stabilizing π-π interactions and the versatile Coulomb interactions dictates the elongation state of the foldamer in the gas phase and emphasizes the adequacy of mass spectrometry tools for the superstructural characterization of desolvated prototypical artificial molecular machines. © 2017 American Chemical Society. [less ▲]

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See detailCoulombic driven multi-conformational aspects of oligorotaxane switches studied by ion mobility mass spectrometry and molecular dynamics
Hanozin, Emeline ULiege; Mignolet, Benoît ULiege; Morsa, Denis ULiege et al

Conference (2017, June)

Introduction Artificial Molecular Machines (AMMs), such as Mechanically Interlocked Molecules (MIMs) and foldamers, have recently raised tremendous interest due to their unique properties. Under the ... [more ▼]

Introduction Artificial Molecular Machines (AMMs), such as Mechanically Interlocked Molecules (MIMs) and foldamers, have recently raised tremendous interest due to their unique properties. Under the influence of an appropriate stimuli (pH, redox potential, light…), such molecules are able to reversibly switch between distinct conformational states. Scientists may capitalize on such exclusive properties to get a better understanding of the biomacromolecular level or to design innovative “smart” materials. At the interface between foldamers and MIMs, oligorotaxanes exhibit a spring-like folded secondary structure with remarkable mechanical and physicochemical properties. In the present study, we use ion mobility coupled with mass spectrometry (IM-MS) to probe the conformational states of differentially charged oligorotaxanes in the gas phase. Method Oligorotaxanes are donor-acceptor polymers composed of a π electron-donating dumbbell over which a discrete number of π electron-accepting tetracationic cyclophanes are threaded. The numerous intra-molecular interactions provide them a highly-stabilized rigid rod-like structure in solution. We use IM-MS as implemented in the Synapt G2 HDMS (Waters, Manchester, UK) to investigate the structure of the ionized oligorotaxanes. Our purposes are to probe (i) the different populations of stable conformers generated according to the charge state z and (ii) the reversibility of an electron-driven or thermal-driven conformational change in the gas phase implemented via an electron transfer or collisional activation process prior to the mobility separation. Our experimental observations are supported by electronic structure optimizations at the PM6 and DFT levels coupled with Born-Oppenheimer Molecular Dynamics simulations. Preliminary data Our results highlight a progressive elongation of the oligorotaxane structure with increasing charge numbers until it reaches a maximum extension state. Matching the experimental data with theoretical simulations, we find that the oligorotaxanes adopt an entropically-favored globular shape at low z. As z increases, coulombic repulsions occurring between the cyclophanes gradually outweigh the stabilizing π-stacking interactions and force the structure to elongate. This process occurs in a multistep fashion, each corresponding to a distinct group of helical-shaped conformers, before it eventually results in a fully stretched structure. On the other hand, our results also highlight that a charge reduction driven by a non-dissociative electron transfer process leads to a refolding of the structure so that it adopts a size similar to its electrospray-generated counterpart when the appropriate number of electrons is added. This observation may be imparted to the gradual decrease of the Coulomb repulsions between the cyclophanes mediated through increasing numbers of transferred electrons. These results suggests that the transition from one conformer to another is reversible so that the electrostatic balance between the cyclophanes may be used to further tune the structural state adopted by this artificial molecular switch. The second stimulus relied on collisional activation whose inelastic component provides a way to build up energy into the accessible vibrational degrees of freedom. The conformational landscapes of such-activated oligorotaxanes ions were found unchanged in term of collision cross section position but the repartition of population was altered with a promotion of the most elongated conformer, provided the absence of selective fragmentation. Altogether, these results highlight the feasibility of handling the elongation state of oligorotaxanes in the gas phase through appropriate inputs and underline its conformational reversibility properties. Novel aspect Stimuli-induced reversible conformational rearrangements of innovative AMMs studied by IM-MS and molecular dynamics in the gas phase. [less ▲]

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See detailFirst Results Using TIMS on Systems Requiring High IMS Resolution
Haler, Jean ULiege; Massonnet, Philippe ULiege; Morsa, Denis ULiege et al

Conference (2016, June 05)

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See detailContribution of Capillary Electrophoresis and Ion Mobility Spectrometry to probe conformational change during desolvation
Far, Johann ULiege; Delvaux, Cédric ULiege; Kune, Christopher ULiege et al

Conference (2016, January 28)

The transfer of ions from the solution to the gas phase is a critical step to produce « native species ». Coming from a highly solvating medium, ionic species will tend to find a new equilibrium ... [more ▼]

The transfer of ions from the solution to the gas phase is a critical step to produce « native species ». Coming from a highly solvating medium, ionic species will tend to find a new equilibrium conformation in the gas phase. The pathway to reach the thermodynamically stable conformation involves crossing potential barriers of different heights. When these barriers are too high compared to the internal energy of the ions, it will result in “partial memories” (as structural preservation) of the conformation in solution. In order to evaluate the effect of the solvent evaporation and of the various collision processes encountered by the ions in the mass spectrometer, we developed two strategies: The first strategy consists in comparing in a single experiment the shape of the ions in solution and in the gas phase. Data are obtained by coupling Capillary Electrophoresis (CE) with Ion Mobility Mass Spectrometry (IMS). Drift times in solution and in the gas phase are directly compared. Deviations from their correlation points out changes in folding upon desolvatation. Preliminary results show that some of peptides issued from tryptic digest of BSA clearly change their conformation during desolvatation. The second strategy consists to monitor the shape of the different conformers observed for the intact cytochrome C during native runs in capillary electrophoresis and “native” ion mobility mass spectrometry, both using a physiological TRIS acetic pH7 buffer compared to a “MS friendly” ammonium acetate pH7 buffer. Finally as preliminary study, we proposed to use homopolymers for better understanding about the folding behavior in gas phase and the resulting shape of these ions using ion mobility spectrometry. [less ▲]

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See detailCoulombic driven multi-conformational aspects of oligorotaxane switches studied by ion mobility mass spectrometry
Hanozin, Emeline ULiege; Mignolet, Benoît ULiege; Morsa, Denis ULiege et al

Conference (2016)

Molecular machines, such as Mechanically Interlocked Molecules (MIMs) and foldamers, have recently raised tremendous interest due to their unique properties. Under the influence of an appropriate stimuli ... [more ▼]

Molecular machines, such as Mechanically Interlocked Molecules (MIMs) and foldamers, have recently raised tremendous interest due to their unique properties. Under the influence of an appropriate stimuli (pH, redox potential, light…), such molecules are able to reversibly switch between distinct conformational states. Scientists may capitalize on such exclusive properties to get a better understanding of the biomacromolecular level or to design innovative “smart” materials. At the edge of foldamers and MIMs, oligorotaxanes exhibit a spring-like folded secondary structure with remarkable mechanical and physicochemical properties. In the present study, we use ion mobility coupled with mass spectrometry (IM-MS) to probe the conformational states of differentially charged oligorotaxanes in the gas phase. Oligorotaxanes are donor-acceptor polymers composed of a π electron-donating dumbbell over which a discrete number of π electron-accepting tetracationic cyclophanes are threaded. The numerous intra-molecular interactions provide them a highly-stabilized rigid rod-like structure in solution. We presently use IM-MS as implemented in the Synapt G2 HDMS (Waters, Manchester, UK) to investigate the structure of the ionized three-ring oligorotaxane. Our purposes are to probe (i) the different populations of stable conformers generated according to the charge state z and (ii) the reversibility of an electron-driven conformational change in the gas phase implemented via an electron transfer process (ETnoD) prior to the mobility separation. Our experimental observations are supported by electronic structure optimizations at the PM6 and DFT levels coupled with Born-Oppenheimer Molecular Dynamic (BOMD) simulations. Our results highlight a progressive elongation of the oligorotaxane structure with increasing charge numbers until it reaches a plateau. Matching the experimental data with theoretical simulations, we find that the oligorotaxanes adopt an entropically-favored globular shape at low z. As z increases, coulombic repulsions occurring between the cyclophanes gradually outweigh the stabilizing π-stacking interactions and force the structure to elongate. This process occurs in a multistep fashion, each corresponding to a distinct group of conformers, before it eventually results in a fully stretched structure. On the other hand, our results also highlight that a charge reduction driven by the ETnoD process leads to a refolding of the structure so that it adopts a size similar to its electrospray-generated counterpart, therefore attesting of the conformational reversibility of olixorotaxanes in the gas phase. Altogether, our results show that the oligorotaxanes adopt different conformers associated with increasing levels of extension as a function of the charge state. The transition from one conformer to another is reversible so that the electrostatic balance between the cyclophanes may be used to further tune the structural state adopted by this switch in the gas phase. [less ▲]

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