Sandy Gewinner

Protomers of Benzocaine: Solvent and Permittivity Dependence

The immediate environment of a molecule can have a profound influence on its properties. Benzocaine, the ethyl ester of para-aminobenzoic acid that finds an application as a local anesthetic, is found to adopt in its protonated form at least two populations of distinct structures in the gas phase, and their relative intensities strongly depend on the properties of the solvent used in the electrospray ionization process. Here, we combine IR-vibrational spectroscopy with ion mobility-mass spectrometry to yield gas-phase IR spectra of simultaneously m/z and drift-time-resolved species of benzocaine. The results allow for an unambiguous identification of two protomeric species: the N- and O-protonated forms. Density functional theory calculations link these structures to the most stable solution and gas-phase structures, respectively, with the electric properties of the surrounding medium being the main determinant for the preferred protonation site. The fact that the N-protonated form of benzocaine can be found in the gas phase is owed to kinetic trapping of the solution-phase structure during transfer into the experimental setup. These observations confirm earlier studies on similar molecules where N- and O-protonation have been suggested.

The new IR and THz FEL facility at the Fritz Haber Institute in Berlin

A mid-infrared oscillator FEL has been commissioned at the Fritz Haber Institute. The accelerator consists of a thermionic gridded gun, a subharmonic buncher, and two S-band standing-wave copper structures. It provides a final electron energy adjustable from 15 to 50 MeV, low longitudinal (< 50 keV ps) and transverse emittance (< 20 πmm mrad), at more than 200 pC bunch charge with a micro-pulse repetition rate of 1 GHz and a macro-pulse length of up to 15 µs. Pulsed radiation with up to 100 mJ macro-pulse energy at about 0.5% FWHM bandwidth is routinely produced in the wavelength range from 4 to 48 µm. A characterization of the FEL performance in terms of pulse energy, bandwidth, and micro-pulse shape of the IR radiation is given. In addition, selected user results are presented. These include, for instance, spectroscopy of bio-molecules (peptides and small proteins) either conformer selected by ion mobility spectrometry or embedded in superfluid helium nano-droplets at 0.4 K, as well as vibrational spectroscopy of mass-selected metal-oxide clusters and protonated water clusters in the gas phase.

An infrared spectroscopy approach to follow β-sheet formation in peptide amyloid assemblies

Amyloidogenic peptides and proteins play a crucial role in a variety of neurodegenerative disorders such as Alzheimers and Parkinsons disease. These proteins undergo a spontaneous transition from a soluble, often partially folded form, into insoluble amyloid fibrils that are rich in β-sheets. Increasing evidence suggests that highly dynamic, polydisperse folding intermediates, which occur during fibril formation, are the toxic species in the amyloid-related diseases. Traditional condensed-phase methods are of limited use for characterizing these states because they typically only provide ensemble averages rather than information about individual oligomers. Here we report the first direct secondary-structure analysis of individual amyloid intermediates using a combination of ion mobility spectrometry-mass spectrometry and gas-phase infrared spectroscopy. Our data reveal that oligomers of the fibril-forming peptide segments VEALYL and YVEALL, which consist of 4-9 peptide strands, can contain a significant amount of β-sheet. In addition, our data show that the more-extended variants of each oligomer generally exhibit increased β-sheet content.

Spectroscopic Identification of a Bidentate Binding Motif in the Anionic Magnesium–CO2 Complex ([ClMgCO2]−)

A magnesium complex incorporating a novel metal-CO2 binding motif is spectroscopically identified. Here we show with the help of infrared photodissociation spectroscopy that the complex exists solely in the [ClMg(η(2) -O2 C)](-) form. This bidentate double oxygen metal-CO2 coordination has previously not been observed in neutral nor in charged unimetallic complexes. The antisymmetric CO2 stretching mode in [ClMg(η(2) -O2 C)](-) is found at 1128 cm(-1) , which is considerably redshifted from the corresponding mode in bare CO2 at 2349 cm(-1) , suggesting that the CO2 moiety has a considerable negative charge (∼1.8 e(-) ). We also employed electronic structure calculations and kinetic analysis to support the interpretation of the experimental results.

Structure and Fluxionality of B13 + Probed by Infrared Photodissociation Spectroscopy

We use cryogenic ion vibrational spectroscopy to characterize the structure and fluxionality of the magic number boron cluster B13+ . The infrared photodissociation (IRPD) spectrum of the D2 -tagged all-11 B isotopologue of B13+ is reported in the spectral range from 435 to 1790 cm-1 and unambiguously assigned to a planar boron double wheel structure based on a comparison to simulated IR spectra of low energy isomers from density-functional-theory (DFT) computations. Born-Oppenheimer DFT molecular dynamics simulations show that B13+ exhibits internal quasi-rotation already at 100 K. Vibrational spectra derived from these simulations allow extracting the first spectroscopic evidence from the IRPD spectrum for the exceptional fluxionality of B13+ .

Site-specific vibrational spectral signatures of water molecules in the magic H3O+(H2O)20 and Cs+(H2O)20 clusters

Significance Understanding the mechanics underlying the diffuse OH stretching spectrum of water is a grand challenge for contemporary physical chemistry. Water clusters play an increasingly important role in this endeavor, as they allow one to freeze and isolate the spectral behavior of relatively large assemblies with well-defined network morphologies. We exploit recently developed, hybrid instruments that integrate laser spectroscopy with cryogenic ion trap mass spectrometry to capture the H3O+ and Cs+ ions in cage structures formed by 20 water molecules. Their infrared spectra reveal a pattern of distinct transitions that is unprecedented for water networks in this size range. Theoretical analysis of these patterns then reveals the intramolecular distortions associated with water molecules at various sites in the 3D cages. Theoretical models of proton hydration with tens of water molecules indicate that the excess proton is embedded on the surface of clathrate-like cage structures with one or two water molecules in the interior. The evidence for these structures has been indirect, however, because the experimental spectra in the critical H-bonding region of the OH stretching vibrations have been too diffuse to provide band patterns that distinguish between candidate structures predicted theoretically. Here we exploit the slow cooling afforded by cryogenic ion trapping, along with isotopic substitution, to quench water clusters attached to the H3O+ and Cs+ ions into structures that yield well-resolved vibrational bands over the entire 215- to 3,800-cm−1 range. The magic H3O+(H2O)20 cluster yields particularly clear spectral signatures that can, with the aid of ab initio predictions, be traced to specific classes of network sites in the predicted pentagonal dodecahedron H-bonded cage with the hydronium ion residing on the surface.

Site-specific vibrational spectral signatures of water molecules in the magic H 3 O + (H 2 O) 20 and Cs + (H 2 O) 20 clusters

Significance Understanding the mechanics underlying the diffuse OH stretching spectrum of water is a grand challenge for contemporary physical chemistry. Water clusters play an increasingly important role in this endeavor, as they allow one to freeze and isolate the spectral behavior of relatively large assemblies with well-defined network morphologies. We exploit recently developed, hybrid instruments that integrate laser spectroscopy with cryogenic ion trap mass spectrometry to capture the H3O+ and Cs+ ions in cage structures formed by 20 water molecules. Their infrared spectra reveal a pattern of distinct transitions that is unprecedented for water networks in this size range. Theoretical analysis of these patterns then reveals the intramolecular distortions associated with water molecules at various sites in the 3D cages. Theoretical models of proton hydration with tens of water molecules indicate that the excess proton is embedded on the surface of clathrate-like cage structures with one or two water molecules in the interior. The evidence for these structures has been indirect, however, because the experimental spectra in the critical H-bonding region of the OH stretching vibrations have been too diffuse to provide band patterns that distinguish between candidate structures predicted theoretically. Here we exploit the slow cooling afforded by cryogenic ion trapping, along with isotopic substitution, to quench water clusters attached to the H3O+ and Cs+ ions into structures that yield well-resolved vibrational bands over the entire 215- to 3,800-cm−1 range. The magic H3O+(H2O)20 cluster yields particularly clear spectral signatures that can, with the aid of ab initio predictions, be traced to specific classes of network sites in the predicted pentagonal dodecahedron H-bonded cage with the hydronium ion residing on the surface.

Charge-induced unzipping of isolated proteins to a defined secondary structure

Abstract Here we present a combined experimental and theoretical study on the secondary structure of isolated proteins as a function of charge state. In infrared spectra of the proteins ubiquitin and cytochrome c, amide I (C=O stretch) and amide II (N–H bend) bands can be found at positions that are typical for condensed‐phase proteins. For high charge states a new band appears, substantially red‐shifted from the amide II band observed at lower charge states. The observations are interpreted in terms of Coulomb‐driven transitions in secondary structures from mostly helical to extended C5‐type hydrogen‐bonded structures. Support for this interpretation comes from simple energy considerations as well as from quantum chemical calculations on model peptides. This transition in secondary structure is most likely universal for isolated proteins that occur in mass spectrometric experiments.

Glycan Fingerprinting via Cold-Ion Infrared Spectroscopy

The diversity of stereochemical isomers present in glycans and glycoconjugates poses a formidable challenge for comprehensive structural analysis. Typically, sophisticated mass spectrometry (MS)-based techniques are used in combination with chromatography or ion-mobility separation. However, coexisting structurally similar isomers often render an unambiguous identification impossible. Other powerful techniques such as gas-phase infrared (IR) spectroscopy have been limited to smaller glycans, since conformational flexibility and thermal activation during the measurement result in poor spectral resolution. This limitation can be overcome by using cold-ion spectroscopy. The vibrational fingerprints of cold oligosaccharide ions exhibit a wealth of well-resolved absorption features that are diagnostic for minute structural variations. The unprecedented resolution of cold-ion spectroscopy coupled with tandem MS may render this the key technology to unravel complex glycomes.

Gas phase vibrational spectroscopy of the protonated water pentamer: the role of isomers and nuclear quantum effects

We use cryogenic ion trap vibrational spectroscopy to study the structure of the protonated water pentamer, H+(H2O)5, and its fully deuterated isotopologue, D+(D2O)5, over nearly the complete infrared spectral range (220-4000 cm-1) in combination with harmonic and anharmonic electronic structure calculations as well as RRKM modelling. Isomer-selective IR-IR double-resonance measurements on the H+(H2O)5 isotopologue establish that the spectrum is due to a single constitutional isomer, thus discounting the recent analysis of the band pattern in the context of two isomers based on AIMD simulations 〈W. Kulig and N. Agmon, Phys. Chem. Chem. Phys., 2014, 16, 4933-4941〉. The evolution of the persistent bands in the D+(D2O)5 cluster allows the assignment of the fundamentals in the spectra of both isotopologues, and the simpler pattern displayed by the heavier isotopologue is consistent with the calculated spectrum for the branched, Eigen-based structure originally proposed 〈J.-C. Jiang, et al., J. Am. Chem. Soc., 2000, 122, 1398-1410〉. This pattern persists in the vibrational spectra of H+(H2O)5 in the temperature range from 13 K up to 250 K. The present study also underscores the importance of considering nuclear quantum effects in predicting the kinetic stability of these isomers at low temperatures.