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The digital revolution sets a milestone in the progressive miniaturization of working devices and in the underlying advent of molecular machines. Foldamers involving mechanically entangled components with modular secondary structures are among the most promising designs for molecular switch‐based applications. Characterizing the nature and dynamics of their intramolecular network following the application of a stimulus is the key to their performance. Here, we use non‐dissociative electron transfer as a reductive stimulus in the gas phase and probe the consecutive co‐conformational transitions of a donor‐acceptor oligorotaxane foldamer using electrospray mass spectrometry interfaced with ion mobility and infrared ion spectroscopy. A comparison of collision cross section distributions for analogous closed‐shell and radical molecular ions sheds light on their respective formation energetics, while variations in their respective infrared absorption bands evidence changes in intramolecular organization as the foldamer becomes more compact. These differences are compatible with the advent of radical‐pairing interactions., Gas‐phase non‐dissociative electron transfer is used for charge reduction of a donor‐acceptor oligorotaxane foldamer (green). The consecutive co‐conformational transition is monitored using ion mobility spectrometry and infrared ion spectroscopy. Comparing the collision cross section distributions (blue) and infrared spectra (red) recorded for analogous closed‐shell and radical systems highlights differences that can be attributed to radical‐pairing interactions.

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.

Modern ion mobility instrumentation is typically operated above the low field limit, which may activate the ions and cause structural rearrangement or fragmentation during 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

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 folding of macromolecules is often assessed with the support of computational chemistry. However, this strategy 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 detecting 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.

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

Disulfide bonds are post-translationnal modifications that can be crucial for the stability and the biological activities of natural peptides. Considering the importance of these disulfide bond-containing peptides, the development of new techniques in order to characterize these modifications is of great interest. For this purpose, collision cross cections (CCS) of a large data set of 118 peptides (displaying various sequences) bearing zero, one, two, or three disulfide bond(s) have been measured in this study at different charge states using ion mobility-mass spectrometry. From an experimental point of view, CCS differences (ΔCCS) between peptides bearing various numbers of disulfide bonds and peptides having no disulfide bonds have been calculated. The ΔCCS calculations have also been applied to peptides bearing two disulfide bonds but different cysteine connectivities (Cys1-Cys2/Cys3-Cys4; Cys1-Cys3/Cys2-Cys4; Cys1-Cys4/Cys2-Cys3). The effect of the replacement of a proton by a potassium adduct on a peptidic structure has also been investigated. Graphical Abstract ᅟ.

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 state...

The dissociation of benzylpyridinium "thermometer" ions is widely used to calibrate the internal energy of ions produced in mass spectrometry. The fragmentation mechanism is usually believed to yield a benzylium cation, although recent studies suggest the possibility of a rearrangement leading to the tropylium isomer, which would compromise the accuracy of energy calibrations. In this study, we used IRMPD spectroscopy to probe the dissociation pathways of the p-(tert-butyl)benzylpyridinium ion. Our results show that the formation of both benzylium and tropylium products is feasible depending on the activation regime and on the reaction time scale. Varying the trapping delays in the hexapole gives insight into a rearrangement mechanism occurring through consecutive reactions with an isomerization from benzylium to tropylium. Our work provides experimental validations for the established calibration procedure and highlights the adequacy of IRMPD spectroscopy to qualitatively resolve gas-phase rearrangement kinetics. [GRAPHICS]

International audience; Traveling wave ion mobility spectrometers (TW IMS) operate at significantly higher fields than drift tube ion mobility spectrometers. Here we measured the fragmentation of the fragile p-methoxybenzylpyridinium ion inside the TW ion mobility cell of the first-generation SYNAPT HDMS spectrometer. The ion’s vibrational internal energy was quantified by a vibrational effective temperature Teff,vib, which is the mean temperature of the ions inside the cell that would result in the same fragmentation yield as observed experimentally. Significant fragmentation of the probe ion inside the TW IMS cell was detected, indicating that field heating of the ions takes place in TW IMS. For typical small molecule IMS conditions, Teff,vib = 555 ± 2 K. The variations of the effective temperature were studied as a function of the IMS parameters, and we found that Teff,vib decreases when the wave height decreases, when the pressure increases, or when the wave speed increases. The energy transfer efficiency of argon is higher than for He, N2 or CO2. Teff,vib being directly related to the ion speed inside the TW IMS, our results also provide new insight on the ion movement in TW IMS. We also discuss the influence of field heating of ions for calibration and structural studies in TW IMS.