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In mass spectrometry-based peptide sequencing, electron transfer dissociation (ETD) and electron capture dissociation (ECD) have become well-established fragmentation methods complementary to collision-induced dissociation. The dominant fragmentation pathways during ETD and ECD primarily involve the formation of c- and z • -type ions by cleavage of the peptide backbone at the N─C α bond, although neutral losses from amino acid side chains have also been observed. Residue-specific neutral side chain losses provide useful information when conducting database searching and de novo sequencing. Here, we use a combination of infrared ion spectroscopy and quantum-chemical calculations to assign the structures of two ETD-generated w-type fragment ions. These ions are spontaneously formed from ETD-generated z • -type fragments by neutral loss of 33 Da in peptides containing a cysteine residue. Analysis of the infrared ion spectra confirms that these z • -ions expel a thiol radical (SH • ) and that a vinyl C═C group is formed at the cleavage site. z • -type fragments containing a Cys residue but not at the cleavage site do not spontaneously expel a thiol radical, but only upon additional collisional activation after ETD., (© 2018 The Authors Journal of Mass Spectrometry Published by John Wiley & Sons Ltd.)

Infrared multiphoton dissociation (IRMPD) spectra of mass selected isolated metal-lumichrome ionic complexes, M(q+)LCn with M(q+) = Li(+), Na(+), K(+), Rb(+), Cs(+), Ag(+) (n = 1), and Mg(2+) (n = 2), are recorded in the fingerprint range. The complexes are generated in an electrospray ionization source coupled to an ion cyclotron mass spectrometer and the IR free electron laser FELIX. Vibrational and isomer assignments of the IRMPD spectra are accomplished by density functional theory calculations at the B3LYP/cc-pVDZ level, which provide insight into the structure, binding energy, bonding mechanism, and spectral properties of the complexes. The two major binding sites identified involve metal bonding to the oxygen atoms of the two available carbonyl groups of LC (denoted O2 and O4). The more stable O4 isomer benefits from an additional interaction with the lone pair of the nearby N5 atom of LC. While M(+)LC with alkali metals are mainly stabilized by electrostatic forces, the Ag(+)LC complex reveals additional stabilization arising from partly covalent contributions. Finally, the interaction of Mg(2+) ions with LC is largely enhanced by the doubled positive charge. The frequencies of the C[double bond, length as m-dash]O stretching modes are a sensitive indicator of both the metal binding site and the metal bond strength.

In an effort to understand the chemical factors that stabilize dianions, experimental and theoretical studies on the stability of the tartrate dianion were performed. Quantum chemical calculations at the coupled cluster level reveal only a metastable state with a possible decomposition pathway (O(2)C-CH(OH)-CH(OH)-CO(2))(2-) → (O(2)C-CH(OH)-CH(OH))(•-) + CO(2) + e(-) explaining the observed gas-phase instability of this dianion. Further theoretical data were collected for the bare dianion, this molecule complexed to water, sodium, and a proton, in both the meso and l forms as well as for the uncomplexed radical anion and neutral diradical. The calculations suggest that the l-tartrate dianion is more thermodynamically stable than the dianion of the meso stereoisomer and that either dianion can be further stabilized by association with a separate species that can help to balance the charge of the molecular complex. Mass spectrometry was then used to measure the energy needed to initiate collisionally induced dissociation of the racemic tartrate dianion and for the proton and sodium adducts of both the racemic and meso form of this molecule. Infrared action spectra of the dianion stereoisomers complexed with sodium were also acquired to determine the influence of the metal ion on the vibrations of the dianions and validate the computationally predicted structures. These experimental data support the theoretical conclusions and highlight the instability of the bare tartrate dianion. From the experimental work, it could also be concluded that the pathway leading to dissociation is under kinetic control because the sodium adduct of the racemic stereoisomer dissociated at lower collisional energy, although it was calculated to be more stable, and that decomposition proceeded via C-C bond dissociation as computationally predicted. Taken together, these data provide insight into the gas-phase stability of the tartrate dianion and highlight the role of adducts in stabilizing this species.

A large variety of 1,2,3-thiadiazoles and 1,2,3-triazoles are used extensively in modern pure and applied organic chemistry as important structural blocks of numerous valuable products. Creation of new methods of synthesis of these isomeric compounds requires the development of reliable analytical tools to reveal the structural characteristics of these novel compounds, which are able to distinguish between isomers. Mass spectrometry (MS) is a clear choice for this task due to its selectivity, sensitivity, informational capacity, and reliability. Here, the application of electrospray ionization (ESI) with ion detection in positive and negative modes was demonstrated to be useful in structural studies. Additionally, interconversion of isomeric 4,5-functionalized 1,2,3-triazoles and 1,2,3-thiadiazoles was demonstrated. Application of accurate mass measurements and tandem mass spectrometry in MS2 and MS3 modes indicated the occurrence of gas-phase rearrangement of 1,2,3-triazoles into 1,2,3-thiadiazoles under (+)ESI-MS/MS conditions, independent of the nature of substituents, in line with the reaction in the condensed phase. Infrared multiple photon dissociation (IRMPD) spectroscopy enabled the establishment of structures of some of the most crucial common fragment ions, including [M+H-N2]+ and [M+H-N2-RSO2]+ species. The (−)ESI-MS/MS experiments were significantly more informative for the sulfonyl alkyl derivatives compared to the sulfonyl aryl ones. However, there was insufficient evidence to confirm the solution-phase transformation of 1,2,3-thiadiazoles into the corresponding 1,2,3-triazoles. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this study, dissociative one‐electron transfer dissociation of [CuII(dien)Y(G/A)W]•2+ [dien = diethylenetriamine; Y(G/A)W = tyrosyl (glycyl/alanyl)tryptophan] was used to generate the tripeptide radical cations [Y(G/A)W]•+; subsequent loss of the Tyr side chain formed [Gα•(G/A)W]+. The π‐centered species [YGWπ•]+ generated the α‐centered species [Gα•GW]+ through Cα–Cβ bond cleavage, as revealed using infrared multiple photon dissociation (IRMPD) measurements and density functional theory (DFT) calculations. Comparisons of experimental and theoretical IR spectra confirmed that both the charge and spin densities of [Y(G/A)Wπ•]+ were delocalized initially at the tryptophan indolyl ring; subsequent formation of the final [Gα•(G/A)W]+ structure gave the highest spin density at the α‐carbon atom of the N‐terminal glycine residue, with a proton solvated by the first amide oxygen atom. The IRMPD mass spectra and action spectra of the [Gα•(G/A)W]+ species were all distinctly different from those of their isomeric [G(G/A)Wπ•]+ species. The mechanism of formation of the captodative [Gα•(G/A)W]+ species—with the charge site separated from the radical site—from [Y(G/A)Wπ•]+ has been elucidated. DFT calculations suggested that the Cα–Cβ bond cleavage of the tyrosine residue in the radical cationic [Y(G/A)Wπ•]+ precursor involves (a) through‐space electron transfer between the indolyl and phenolic groups; (b) formation of proton‐bound dimers through Cα–Cβ cleavage of the tyrosine residue; and (c) a concerted proton rearrangement from the phenolic OH group to the carboxyl group and formation of the α‐carbon‐centered product [Gα•(G/A)W]+ through hydrogen bond cleavage. The barriers for the electron transfer (a), the Cα–Cβ cleavage (b), and the protonation rearrangement (c) were 12.8, 26.5, and 10.3 kcal mol−1, respectively. [ABSTRACT FROM AUTHOR]

Breslow intermediates (BIs) are the crucial nucleophilic amino enol intermediates formed from electrophilic aldehydes in the course of N‐heterocyclic carbene (NHC)‐catalyzed umpolung reactions. Both in organocatalytic and enzymatic umpolung, the question whether the Breslow intermediate exists as the nucleophilic enol or in the form of its electrophilic keto tautomer is of utmost importance for its reactivity and function. Herein, the preparation of charge‐tagged Breslow intermediates/keto tautomers derived from three different types of NHCs (imidazolidin‐2‐ylidenes, 1,2,4‐triazolin‐5‐ylidenes, thiazolin‐2‐ylidenes) and aldehydes is reported. An ammonium charge tag is introduced through the aldehyde unit or the NHC. ESI‐MS IR ion spectroscopy allowed the unambiguous conclusion that in the gas phase, the imidazolidin‐2‐ylidene‐derived BI indeed exists as a diamino enol, while both 1,2,4‐triazolin‐5‐ylidenes and thiazolin‐2‐ylidenes give the keto tautomer. This result coincides with the tautomeric states observed for the BIs in solution (NMR) and in the crystalline state (XRD), and is in line with our earlier calculations on the energetics of BI keto–enol equilibria. [ABSTRACT FROM AUTHOR]

Distinguishing positional isomers, such as compounds having different substitution patterns on an aromatic ring, presents a significant challenge for mass spectrometric analyses and is a frequently encountered difficulty in, for example, drug metabolism research. In contrast to mass spectrometry, IR spectroscopy is a well-known and powerful tool in the distinction of ortho-, meta- and para-isomers, but is not applicable to low-abundance compounds in complex mixtures such as often targeted in bioanalytical studies. Here, we demonstrate the use of infrared ion spectroscopy (IRIS) as a novel method that facilitates the differentiation between positional isomers of disubstituted phenyl-containing compounds and that can be applied in mass spectrometry-based complex mixture analysis. By analyzing different substitution patterns over several sets of isomeric compounds, we show that IRIS is able to consistently probe the diagnostic CH out-of-plane vibrations that are sensitive to positional isomerism. We show that these modes are largely independent of the chemical functionality contained in the ring substituents and of the type of ionization. We also show that IRIS spectra often identify the positional isomer directly, even in the absence of reference spectra obtained from physical standards or from computational prediction. We foresee that this method will be generally applicable to the identification of disubstituted phenyl-containing compounds. [ABSTRACT FROM AUTHOR]

Aims. We investigate the possible role of polycyclic aromatic hydrocarbons (PAHs) as a sink for deuterium in the interstellar medium (ISM) and study UV photolysis as a potential underlying chemical process in the variations of the deuterium fractionation in the ISM. Methods. The UV photo-induced fragmentation of various isotopologs of deuterium-enriched, protonated anthracene and phenanthrene ions (both C14H10 isomers) was recorded in a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer. Infrared multiple photon dissociation spectroscopy using the Free-Electron Laser for Infrared eXperiments was applied to provide IR spectra. Infrared spectra calculated using density functional theory were compared to the experimental data to identify the isomers present in the experiment. Transition-state energies and reaction rates were also calculated and related to the experimentally observed fragmentation product abundances. Results. The photofragmentation mass spectra for both UV and IRMPD photolysis only show the loss of atomic hydrogen from [D-C14H10]+, whereas [H-C14D10]+ shows a strong preference for the elimination of deuterium. Transition state calculations reveal facile 1,2-H and -D shift reactions, with associated energy barriers lower than the energy supplied by the photo-excitation process. Together with confirmation of the ground-state structures via the IR spectra, we determined that the photolytic processes of the two different PAHs are largely governed by scrambling where the H and the D atoms relocate between different peripheral C atoms. The 0.1 eV difference in zero-point energy between C-H and C-D bonds ultimately leads to faster H scrambling than D scrambling, and increased H atom loss compared to D atom loss. Conclusions. We conclude that scrambling is common in PAH cations under UV radiation. Upon photoexcitation of deuteriumenriched PAHs, the scrambling results in a higher probability for the aliphatic D atom to migrate to a strongly bound aromatic site, protecting it from elimination. We speculate that this could lead to increased deuteration as a PAH moves towards more exposed interstellar environments. Also, large, compact PAHs with an aliphatic C-HD group on solo sites might be responsible for the majority of aliphatic C-D stretching bands seen in astronomical spectra. An accurate photochemical model of PAHs that considers deuterium scrambling is needed to study this further. [ABSTRACT FROM AUTHOR]

N‐Heterocyclic carbene (NHC) ligands are ubiquitously utilized in catalysis. A common catalyst design model assumes strong M–NHC binding in this metal–ligand framework. In contrast to this common assumption, we demonstrate here that lability and controlled cleavage of the M−NHC bond (rather than its stabilization) could be more important for high‐performance catalysis at low catalyst concentrations. The present study reveals a dynamic stabilization mechanism with labile metal–NHC binding and [PdX3]−[NHC‐R]+ ion pair formation. Access to reactive anionic palladium intermediates formed by dissociation of the NHC ligands and plausible stabilization of the molecular catalyst in solution by interaction with the [NHC‐R]+ azolium ion is of particular importance for an efficient and recyclable catalyst. These ionic Pd/NHC complexes allowed for the first time the recycling of the complex in a well‐defined form with isolation at each cycle. Computational investigation of the reaction mechanism confirms a facile formation of NHC‐free anionic Pd in polar media through either Ph–NHC coupling or reversible H–NHC coupling. The present study formulates novel ideas for M/NHC catalyst design. [ABSTRACT FROM AUTHOR]

Abstract: Brønsted acids and protic solvents mediate acyl transfer, known as the Mumm rearrangement, from imidates to the corresponding acylamides. This represents a key step in several reactions, for example, the Ugi four‐component reaction (U‐4CR) and Passerini three‐component reaction (P‐3CR). Herein, an unprecedented break of the non‐reversibility of the Mumm rearrangement is reported. A combination of electrospray tandem mass spectrometry (ESI‐MS/MS), infrared multiphoton dissociation (IRMPD) ion spectroscopy and theoretical calculations demonstrates the occurrence of the retro‐Mumm rearrangement of protonated isopeptides in the gas phase. In the gas phase, the extra proton acquired during ESI promotes the backward isomerisation reaction in a catalytic fashion. [ABSTRACT FROM AUTHOR]

Proton transfer in the conjugate acid cation of a symmetric diether, 1,5-dimethoxy-3,3-dimethylpentane ( 1 ), is explored both theoretically and experimentally via IRMPD spectroscopy. The optimized geometry of the cation has one oxygen pyramidalized (sum of the three angles Σ = 345°), while the other oxygen has a virtually planar geometry (if one includes the strongly hydrogen bonded O⋯H, the three bond angles sum to Σ′ = 357°). Assuming that this geometry is not preserved upon intramolecular proton transfer from one oxygen to the other, two alternatives remain: either the two oxygens trade geometries (Σ and Σ′ change places via a transition state that has a mirror plane of symmetry) or else both oxygens become pyramidalized. Because the asymmetric stretch couples with other vibrational modes of the cation, special attention is paid to the classical turning points at the zero point level corresponding to the lowest frequency vibration that shows a deuterium isotope effect, which occurs experimentally around 895 cm −1 . This stretching vibration has a lower frequency than the bands assigned to O⋯H O bends, and it shifts to still lower frequency in the deuteronated ion. Because a normal modes calculation matches this vibration, we conclude that the potential energy surface matches a single-well and does not correspond to a double-well minimum. [ABSTRACT FROM AUTHOR]

CH stretches in hydrocarbon cations often shift to lower frequencies relative to neutral molecules, because they do not have sufficient electrons to give every bond an electron pair. A parallel effect in negatively charged species has not been previously observed. Here we show that CH bond weakening occurs in alkoxide anions as a consequence of hyperconjugation. The reasoning differs somewhat from the case of positively charged ions, but the net effect is the same: to lower CH stretching frequencies by hundreds of wavenumbers. [ABSTRACT FROM AUTHOR]

Herein we report the first application of infrared multiple-photon dissociation (IRMPD) spectroscopy to study noncovalent interactions in organocatalysis. Phenylalanine-derived iminium ions, central to numerous organocatalytic processes, display dynamic conformational behavior as a consequence of stabilizing noncovalent interactions (e.g., CH-π, π-π). Electronic modulation of the aryl ring causes notable variation in the conformation; this can be detected spectroscopically and correlated with enantioselectivity. Given that these interactions, which orchestrate stereoinduction, encode for specific conformers (I, II, or III), a diagnostic IRMPD spectrum is generated: the C=O stretching frequency of the imidazole carbonyl group serves as a diagnostic marker. The calculated conformers and their respective spectra can be compared with experimental data. Consequently, valuable insight into the ubiquitous noncovalent interactions associated with MacMillan-catalyst-derived α,β-unsaturated iminium ions can be obtained in the absence of solvent or counterion effects. A preliminary structure-catalysis correlation is disclosed, thus demonstrating the potential of this approach for studying reactive intermediates and facilitating catalyst design. [ABSTRACT FROM AUTHOR]

The structure and reactivity of the N-acetyl-cysteine radical cation and anion were studied using ion-molecule reactions, infrared multi-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The radical cation was generated by first nitrosylating the thiol of N-acetyl-cysteine followed by the homolytic cleavage of the S-NO bond in the gas phase. IRMPD spectroscopy coupled with DFT calculations revealed that for the radical cation the radical migrates from its initial position on the sulfur atom to the α-carbon position, which is 2.5 kJ mol lower in energy. The radical migration was confirmed by time-resolved ion-molecule reactions. These results are in contrast with our previous study on cysteine methyl ester radical cation (Osburn et al., Chem. Eur. J. , 17, 873-879) and the study by Sinha et al. for cysteine radical cation ( Phys. Chem. Chem. Phys. , 12, 9794-9800) where the radical was found to stay on the sulfur atom as formed. A similar approach allowed us to form a hydrogen-deficient radical anion of N-acetyl-cysteine, (M - 2H). IRMPD studies and ion-molecule reactions performed on the radical anion showed that the radical remains on the sulfur, which is the initial and more stable (by 63.6 kJ mol) position, and does not rearrange. [ABSTRACT FROM AUTHOR]

Cover Feature: Breslow Intermediates (Amino Enols) and Their Keto Tautomers: First Gas-Phase Characterization by IR Ion Spectroscopy (Chem. Eur. J. 8/2021) Keywords: Breslow intermediate; density functional calculations; IR spectroscopy; mass spectrometry; umpolung EN Breslow intermediate density functional calculations IR spectroscopy mass spectrometry umpolung 2552 2552 1 02/08/21 20210205 NES 210205 B Breslow Intermediates b are of pivotal importance for chemical and biological Umpolung reactions catalyzed by N-heterocyclic carbenes (NHCs). The enol-ketone tautomerism of a number of NHC-aldehyde combinations, crucial for their chemical reactivity, have been determined in the gas-phase and interpreted by DFT calculations. [Extracted from the article]

B Understanding dynamic interplay b between the molecular and ionic forms of metal/N-heterocyclic carbene (M/NHC) complexes is the key to develop efficient catalysts with N-heterocyclic carbene ligands. B Understanding dynamic interplay b between the molecular and ionic forms of metal/N-heterocyclic carbene (M/NHC) complexes is the key to develop efficient catalysts with N-heterocyclic carbene ligands. Carbene ligands, dynamic catalysis, electrospray ionization, mass spectrometry, Mizoroki-Heck reaction. [Extracted from the article]

Abstract: Collision-induced dissociation (CID) of the peptide alanine-4-aminomethylbenzoic acid-glycine, A(AMBz)G generates a prominent b2 ion despite a previous report [E.R. Talaty, T.J. Cooper, S.M. Osburn, M.J. Van Stipdonk, Collision-induced dissociation of protonated tetrapeptides containing β-alanine, γ-aminobutyric acid, ɛ-aminocaproic acid or 4-aminomethylbenzoic acid residues, Rapid Commun. Mass Spectrom. 20 (2006) 3443–3455.] which showed that incorporation of the aromatic amino acid into a peptide sequence inhibits generation of b n ions formed by cleavage to the immediate C-terminal side of the residue. Infrared multiple photon dissociation (IRMPD) spectroscopy and density functional theory (DFT) calculations suggest that the b2 ion generated from A(AMBz)G has an acylium structure. The b2 ion generated from (AMBz)AG, in which the aromatic residue is situated at the amino-terminus, is instead a conventional oxazolone. [Copyright &y& Elsevier]

Abstract: All eight d-aldohexoses and aldohexoses derived from the non-reducing end of disaccharides were investigated by variable-wavelength infrared multiple-photon dissociation (IRMPD) as anions in the negative-ion mode. Spectroscopic evidence supports the existence of a relatively abundant open-chain configuration of the anions in the gas phase, based on the observation of a significant carbonyl absorption band near 1710cm−1. The abundance of the open-chain configuration of the aldohexose anions was approximately 1000-fold or greater than that of the neutral sugars in aqueous solution. This provides an explanation as to why it has not been possible to discriminate the anomeric configuration of aldohexose anions in the gas phase when derived from the non-reducing sugar of a disaccharide. Evidence from photodissociation spectra also indicates that the different aldohexoses yield product ions with maximal abundances at different wavelengths, and that the carbonyl stretch region is useful for differentiation of sugar stereochemistries. Quantum-chemical calculations indicate relatively low energy barriers to intramolecular proton transfer between hydroxyl groups and adjacent alkoxy sites located on open-chain sugar anions, suggesting that an ensemble of alkoxy charge locations contributes to their observed photodissociation spectra. Ring opening of monosaccharide anions and interconversion among configurations is an inherent property of the ions themselves and occurs in vacuo independent of solvent participation. [Copyright &y& Elsevier]

Combining the individual analytical strengths of mass spectrometry and infrared spectroscopy, infrared ion spectroscopy is increasingly recognized as a powerful tool for small-molecule identification in a wide range of analytical applications. Mass spectrometry is itself a leading analytical technique for small-molecule identification on the merit of its outstanding sensitivity, selectivity and versatility. The foremost shortcoming of the technique, however, is its limited ability to directly probe molecular structure, especially when contrasted against spectroscopic techniques. In infrared ion spectroscopy, infrared vibrational spectra are recorded for mass-isolated ions and provide a signature that can be matched to reference spectra, either measured from standards or predicted using quantum-chemical calculations. Here we present an overview of the potential for this technique to develop into a versatile analytical method for identifying molecular structures in mass spectrometry-based analytical workflows. In this tutorial perspective, we introduce the reader to the technique of infrared ion spectroscopy and highlight a selection of recent experimental advances and applications in current analytical challenges, in particular in the field of untargeted metabolomics. We report on the coupling of infrared ion spectroscopy with liquid chromatography and present experiments that serve as proof-of-principle examples of strategies to address outstanding challenges. Image 1 • IR ion spectroscopy (IRIS) provides a fingerprint for peaks in a mass spectrum. • The IR fingerprint is a sensitive diagnostic for the molecular structure. • Identification through reference spectra from standards or from computation. • IRIS can be integrated in analytical MS workflows including MSn and LC-MS. • A tutorial on IRIS and selected applications in untargeted metabolomics is presented. [ABSTRACT FROM AUTHOR]

The fragmentation chemistry of protonated sulfoserine was probed using a combination of collision-induced dissociation (CID) mass spectrometry, infrared multiple photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The IRMPD spectra of the dominant fragment ions at m / z 106 and 88 ( i.e. , loss of SO 3 and H 2 SO 4 ) were obtained and used to determine the corresponding structures. By comparison to a synthetic standard and calculations, it was determined that the m / z 106 ion is structurally identical to protonated serine. The m / z 88 fragment ion was assigned an aziridine structure based on a comparison to theory, analogous to the structure previously proposed by others for phosphoric acid loss from phosphoserine. This work provides the first spectroscopic insights into the dissociation pathways of a sulfated amino acid, laying the groundwork for future studies on related amino acids and peptides with this important, labile post-translational modification. [ABSTRACT FROM AUTHOR]