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Glutathione is a biologically abundant and redox active tripeptide that serves to protect cells from oxidative stress and rid the body of toxic heavy metals. The present study examines the coordination complexes of glutathione (GSH) with metals that are central to redox processes in biology, Zn, Cu, and Fe, using infrared multiple photon dissociation (IRMPD) action spectroscopy with a free electron laser. For all three metals, a complex between the metal dication and deprotonated GSH was formed, M(GSHH)+. The experimental IRMPD spectra were compared to scaled harmonic vibrational spectra calculated at the MP2/6-311+G(d,p) level of theory after thorough exploration of conformational space using a simulated annealing protocol. Interestingly, spectra calculated at the B3LYP or oB97XD level do not match experiment as well. These findings offer the first gas-phase spectroscopic evidence for how the biologically relevant metal ions coordinate with glutathione. There are spectral features that are common to all three metals, however, noting the differences in the strengths of the common features between the three metals enables an assessment of the preference or specificity that each individual metal has for a given coordination site. Additionally, all three metals form structures where the deprotonated thiol of the cysteine side chain coordinates with the metal center, which is consistent with the involvement of the thiol site in biologically relevant redox chemistry. Introduction Glutathione (L-g-glutamyl-L-cysteinylglycine, GSH) is a biologically abundant tripeptide. [ABSTRACT FROM AUTHOR]

Infrared emission features are observed towards diverse astronomical objects in the interstellar medium (ISM). Generally, the consensus is that these IR features originate from polycyclic aromatic hydrocarbons (PAHs) and are hence named aromatic infrared bands (AIBs). More recently, it has been suggested that nitrogen substituted PAHs (PANHs) contribute to the AIBs as well and it has even been shown that nitrogen inclusion in PAHs can improve the match with the AIBs, specifically around the 6.2 μm feature. In order to determine which specific molecules or functional groups are at the origin of the AIBs, IR spectra of various PA(N)Hs are experimentally and computationally studied. In this work we expand on the spectroscopic investigation of PANHs by presenting the gas-phase mid-IR spectra of 1,5,9-triazacoronene˙+ (TAC˙+, m/z 303), a threefold nitrogenated congener of coronene˙+, its protonated derivative TACH+ (m/z 304) and the product that forms when water adds to dehydrogenated TAC˙+[TAC–H + H2O]+ (m/z 320). We analyze the mid-IR spectra by comparing them with vibrational modes calculated at the B3LYP/6-311++G(d,p) level a theory and we present a possible geometry for [TAC–H + H2O]+. The TAC˙+ mid-IR spectrum is compared to that of coronene˙+ and is demonstrated to be remarkably similar. We put TAC˙+ and TACH+ into astronomical context by comparing their recorded mid-IR spectra to observed ISM spectra of four spectral classes. From this we conclude that TAC˙+ and TACH+ could both contribute to the AIBs, with TACH+ being a more likely contributor than TAC˙+. [ABSTRACT FROM AUTHOR]

Herein, we explore the generation and characterization of the radical cations of glycylphenylalanylglycine, or [GFG]•+, formed via dissociative electron-transfer reaction from the tripeptide to copper(II) within a ternary complex. A comprehensive investigation employing isotopic labeling, infrared multiple-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations elucidated the details and energetics in formation of the peptide radical cations as well as their dissociation products. Unlike conventional aromatic-containing peptide radical cations that primarily form canonical π-radicals, our findings reveal that 75% of the population of the experimentally produced [GFG]•+ precursors are [GFα•G]+, where the radical resides on the middle α-carbon of the phenylalanyl residue. This unexpected isomeric ion has an enthalpy of 6.8 kcal/mol above the global minimum, which has an N-terminal captodative structure, [Gα•FG]+, comprising 25% of the population. The [b₂-H]•+ product ions are also present in a ratio of 75/25 from [GFα•G]+/ [Gα•FG]+, the results of which are obtained from matches between the IRMPD action spectrum and predicted IR absorption spectra of the [b₂-H]•+ candidate structures, as well as from IRMPD isomer population analyses. [ABSTRACT FROM AUTHOR]

Cored wire is a widespread technology used for performing additions into liquid metal baths as an alternative to bulk-additions. A laboratory-scale study was performed in which the kinetics of assimilation of cored wire in liquid steel baths were studied. An original dataset of positions of the wire/melt interface of cored wire as a function of the time and steel bath temperature was produced. The dataset was compared against results of simulations made with a transient 1D (radial) thermal model of the assimilation of cored wire, and demonstrated reasonable agreement. Hence, this paper provides a dataset that can be used as a resource for the validation of future developments in the field of modeling cored wire injection into liquid metal baths. [ABSTRACT FROM AUTHOR]

Attaining complete anomeric control is still one of the biggest challenges in carbohydrate chemistry. Glycosyl cations such as oxocarbenium and dioxanium ions are key intermediates of glycosylation reactions. Characterizing these highly-reactive intermediates and understanding their glycosylation mechanisms are essential to the stereoselective synthesis of complex carbohydrates. Although C-2 acyl neighbouring-group participation has been well-studied, the reactive intermediates in more remote participation remain elusive and are challenging to study. Herein, we report a workflow that is utilized to characterize rhamnosyl 1,3-bridged dioxanium ions derived from C-3 p-anisoyl esterified donors. First, we use a combination of quantum-chemical calculations and infrared ion spectroscopy to determine the structure of the cationic glycosylation intermediate in the gas-phase. In addition, we establish the structure and exchange kinetics of highly-reactive, low-abundance species in the solution-phase using chemical exchange saturation transfer, exchange spectroscopy, correlation spectroscopy, heteronuclear single-quantum correlation, and heteronuclear multiple-bond correlation nuclear magnetic resonance spectroscopy. Finally, we apply C-3 acyl neighbouring-group participation to the synthesis of complex bacterial oligosaccharides. This combined approach of finding answers to fundamental physical-chemical questions and their application in organic synthesis provides a robust basis for elucidating highly-reactive intermediates in glycosylation reactions. Characterizing highly-reactive glycosyl cation intermediates and understanding their glycosylation mechanisms are essential to the stereoselective synthesis of complex carbohydrates. Here the authors report a workflow that is utilized to characterize rhamnosyl 1,3-bridged dioxanium ions derived from C-3 p-anisoyl esterified donors. [ABSTRACT FROM AUTHOR]

Modern untargeted mass spectrometry (MS) analyses quickly detect and resolve thousands of molecular compounds. Although features are readily annotated with a molecular formula in high-resolution small-molecule MS applications, the large majority of them remains unidentified in terms of their full molecular structure. Collision-induced dissociation tandem mass spectrometry (CID-MS2) provides a diagnostic molecular fingerprint to resolve the molecular structure through a library search. However, for de novo identifications, one must often rely on in silico generated MS2 spectra as reference. The ability of different in silico algorithms to correctly predict MS2 spectra and thus to retrieve correct molecular structures is a topic of lively debate, for instance in the CASMI contest. Underlying the predicted MS2 spectra are the in silico generated product ion structures, which are normally not used in de novo identification, but which can serve to critically assess the fragmentation algorithms. Here we evaluate in silico generated MSn product ion structures by comparison with structures established experimentally by infrared ion spectroscopy (IRIS). For a set of three dozen product ion structures from five precursor molecules, we find that virtually all fragment ion structure annotations in three major in silico MS2 libraries (HMDB, METLIN, mzCloud) are incorrect and caution the reader against their use for structure annotation of MS/MS ions. Collision-induced dissociation tandem mass spectrometry offers to resolve molecular structures through library searches, however, for de novo identifications, one must often rely on in silico-generated spectra as reference. Here, the authors evaluate in silico generated MSn product ion structures by comparison with spectroscopically established structures and find that for 36 randomly selected MS/MS product ions, the vast majority of annotations in three major libraries are incorrect, primarily due to unaccounted for cyclization rearrangements. [ABSTRACT FROM AUTHOR]

Proton and hydrogen-bonded networks sustain a broad range of structural and charge transfer processes in supramolecular materials. The modelling of proton dynamics is however challenging and demands insights from prototypical benchmark systems. The intramolecular H-bonding networks induced by either protonation or deprotonation of 3-hydroxyglutaric acid provide intriguing case studies of correlated proton dynamics. The vibrational signatures associated with the fluxional proton bonding and its coupling with the hydroxyglutaric backbone are investigated here with infrared action ion spectroscopy experiments and Born–Oppenheimer molecular dynamics (BOMD) computations. Despite the formally similar symmetry of protonated and deprotonated hydroxyglutaric acid, the relative proton affinities of the oxygen centers of the carboxylic and carboxylate groups with respect to that of the central hydroxyl group lead to distinct proton dynamics. In the protonated acid, a tautomeric arrangement of the type HOCO·[HOH]+·OCOH is preferred with the proton binding tighter to the central hydroxyl moiety and the electronic density being shared between the two nearly symmetric H-bonds with the carboxylic end groups. In the deprotonated acid, the asymmetric [OCO]−·HO·HOCO configuration is more stable, with a stronger H-bonding on the bare carboxylate end. Both systems display active backbone dynamics and concerted Grothuss-like proton motions, leading to diffuse band structures in their vibrational spectra. These features are accurately reproduced by the BOMD computations. [ABSTRACT FROM AUTHOR]

Intramolecular radical and proton migration in the gas phase are important processes driving the dissociation reactions underlying common tandem mass spectrometry processes, such as collision-induced and electron-induced dissociation reactions (CID and ExD). Mechanistic insights in these processes requires experiments that probe the molecular structures of ions along the reaction pathways, usually combined with quantum-chemical calculations. The combination of ion trap mass spectrometry with IR laser spectroscopy, pioneered among others by Dieter Gerlich, provides a particularly effective method to explore details of the ion structures. In this work, we employ infrared multiple-photon dissociation (IRMPD) spectroscopy and density functional theory (DFT) calculations to probe the reactant and product ion structures of a homolytic bond cleavage reaction. First, we employ IRMPD spectroscopy to establish that protonation of the 4-bromoaniline precursor occurs on the amine moiety and then that C-Br homolytic cleavage produces the π-radical cation of aniline. Transition-state calculations are performed to compare the various pathways that connect reactant and product ions, including both proton and radical transfer mechanisms. [ABSTRACT FROM AUTHOR]

The identification of biotransformation products of drug compounds is a crucial step in drug development. Over the last decades, liquid chromatography‐mass spectrometry (LC‐MS) has become the method of choice for metabolite profiling because of its high sensitivity and selectivity. However, determining the full molecular structure of the detected metabolites, including the exact biotransformation site, remains challenging on the basis of MS alone. Here we explore infrared ion spectroscopy (IRIS) as a novel MS‐based method for the elucidation of metabolic pathways in drug metabolism research. Using the drug midazolam as an example, we identify several biotransformation products directly from an in vitro drug incubation sample. We show that IR spectra of the aglycone MS/MS fragment ions of glucuronide metabolites establish a direct link between detected phase I and phase II metabolites. Moreover, using quantum‐chemically computed IR spectra of candidate structures, we are able to assign the exact sites of biotransformation in absence of reference standards. Additionally, we demonstrate the utility of IRIS for structural elucidation by identifying several ring‐opened midazolam derivatives formed in an acidic environment. [ABSTRACT FROM AUTHOR]

We used next‐generation metabolic screening to identify new biomarkers for improved diagnosis and pathophysiological understanding of glucose transporter type 1 deficiency syndrome (GLUT1DS), comparing metabolic cerebrospinal fluid (CSF) profiles from 12 patients to those of 116 controls. This confirmed decreased CSF glucose and lactate levels in patients with GLUT1DS and increased glutamine at group level. We identified three novel biomarkers significantly decreased in patients, namely gluconic + galactonic acid, xylose‐α1‐3‐glucose, and xylose‐α1‐3‐xylose‐α1‐3‐glucose, of which the latter two have not previously been identified in body fluids. CSF concentrations of gluconic + galactonic acid may be reduced as these metabolites could serve as alternative substrates for the pentose phosphate pathway. Xylose‐α1‐3‐glucose and xylose‐α1‐3‐xylose‐α1‐3‐glucose may originate from glycosylated proteins; their decreased levels are hypothetically the consequence of insufficient glucose, one of two substrates for O‐glucosylation. Since many proteins are O‐glucosylated, this deficiency may affect cellular processes and thus contribute to GLUT1DS pathophysiology. The novel CSF biomarkers have the potential to improve the biochemical diagnosis of GLUT1DS. Our findings imply that brain glucose deficiency in GLUT1DS may cause disruptions at the cellular level that go beyond energy metabolism, underlining the importance of developing treatment strategies that directly target cerebral glucose uptake. [ABSTRACT FROM AUTHOR]

Uronic acids are carbohydrates carrying a terminal carboxylic acid and have a unique reactivity in stereoselective glycosylation reactions. Herein, the competing intramolecular stabilization of uronic acid cations by the C‐5 carboxylic acid or the C‐4 acetyl group was studied with infrared ion spectroscopy (IRIS). IRIS reveals that a mixture of bridged ions is formed, in which the mixture is driven towards the C‐1,C‐5 dioxolanium ion when the C‐5,C‐2‐relationship is cis, and towards the formation of the C‐1,C‐4 dioxepanium ion when this relation is trans. Isomer‐population analysis and interconversion barrier computations show that the two bridged structures are not in dynamic equilibrium and that their ratio parallels the density functional theory computed stability of the structures. These studies reveal how the intrinsic interplay of the different functional groups influences the formation of the different regioisomeric products. [ABSTRACT FROM AUTHOR]

Hyperprolinemia type II (HPII) is an inborn error of metabolism due to genetic variants in ALDH4A1, leading to a deficiency in Δ-1-pyrroline-5-carboxylate (P5C) dehydrogenase. This leads to an accumulation of toxic levels of P5C, an intermediate in proline catabolism. The accumulating P5C spontaneously reacts with, and inactivates, pyridoxal 5'-phosphate, a crucial cofactor for many enzymatic processes, which is thought to be the pathophysiological mechanism for HPII. Here, we describe the use of a combination of LC-QTOF untargeted metabolomics, NMR spectroscopy and infrared ion spectroscopy (IRIS) to identify and characterize biomarkers for HPII that result of the spontaneous reaction of P5C with malonic acid and acetoacetic acid. We show that these biomarkers can differentiate between HPI, caused by a deficiency of proline oxidase activity, and HPII. The elucidation of their molecular structures yields insights into the disease pathophysiology of HPII. Combined metabolomics, NMR, and, IRIS identify biomarkers of hyperprolinemia type II (HPII) distinct from HPI and similar metabolic signatures as in patients with pyridoxine-dependent epilepsy. [ABSTRACT FROM AUTHOR]

N‐Acyliminium ions are highly reactive intermediates that are important for creating CC‐bonds adjacent to nitrogen atoms. Here we report the characterization of cyclic N‐acyliminium ions in the gas phase, generated by collision induced dissociation tandem mass spectrometry followed by infrared ion spectroscopy using the FELIX infrared free electron laser. Comparison of DFT calculated spectra with the experimentally observed IR spectra provided valuable insights in the conformations of the N‐acyliminium ions. [ABSTRACT FROM AUTHOR]

The gas-phase structures of protonated unsymmetrical 1,1-dimethylhydrazine (UDMH) and the proton-bound dimers of UDMH and hydrazine are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light generated by a free electron laser and an optical parametric oscillator laser system. To identify the structures present in the experimental studies, the measured IRMPD spectra are compared to spectra calculated at the B3LYP-GD3BJ/6-311+G(d,p) level of theory. These comparisons show that protonated UDMH binds the proton at the methylated nitrogen atom (α) with two low-lying α conformers probably being populated. For (UDMH)2H+, the proton is shared between the methylated nitrogen atoms with several low-lying α conformers likely to be populated. Higher-lying conformers of (UDMH)2H+ in which the proton is shared between α and β (unmethylated) nitrogen atoms cannot be ruled out on the basis of the IRPMD spectrum. For (N2H4)2H+, there are four low-lying conformers that all reproduce the IRMPD spectrum reasonably well. As hydrazine and UDMH see usage as fuels for rocket engines, such spectra are potentially useful as a means of remotely monitoring rocket launches, especially in cases of unsuccessful launches where environmental hazards need to be assessed. [ABSTRACT FROM AUTHOR]

Infrared ion spectroscopy is increasingly recognized as a method to identify mass spectrometry-detected analytes in many (bio)chemical areas and its integration in analytical laboratories is now on the horizon. Commercially available quadrupole ion trap mass spectrometers are attractive ion spectroscopy platforms but operate at relatively high pressures. This promotes collisional deactivation which directly interferes with the multiple-photon excitation process required for ion spectroscopy. To overcome this, infrared lasers having a high instantaneous power are required and therefore a majority of analytical studies have been performed at infrared free electron laser facilities. Proliferation of the technique to routine use in analytical laboratories requires table-top infrared lasers and optical parametric oscillators (OPOs) are the most suitable candidates, offering both relatively high intensities and reasonable spectral tuning ranges. Here, we explore the potential of a range of commercially available high-power OPOs for ion spectroscopy, comparing systems with repetition rates of 10 Hz, 20 kHz, 80 MHz and a continuous-wave (cw) system. We compare the performance for various molecular ions and show that the kHz and MHz repetition-rate systems outperform cw and 10 Hz systems in photodissociation efficiency and offer several advantages in terms of cost-effectiveness and practical implementation in an analytical laboratory not specialized in laser spectroscopy. [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]

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]

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]

The identification of disease biomarkers plays a crucial role in developing diagnostic strategies for inborn errors of metabolism and understanding their pathophysiology. A primary metabolite that accumulates in the inborn error phenylketonuria is phenylalanine, however its levels do not always directly correlate with clinical outcomes. Here we combine infrared ion spectroscopy and NMR spectroscopy to identify the Phe-glucose Amadori rearrangement product as a biomarker for phenylketonuria. Additionally, we find analogous amino acid-glucose metabolites formed in the body fluids of patients accumulating methionine, lysine, proline and citrulline. Amadori rearrangement products are well-known intermediates in the formation of advanced glycation end-products and have been associated with the pathophysiology of diabetes mellitus and ageing, but are now shown to also form under conditions of aminoacidemia. They represent a general class of metabolites for inborn errors of amino acid metabolism that show potential as biomarkers and may provide further insight in disease pathophysiology. Rianne van Outersterp et al. combine mass spectrometry, NMR, and infrared ion spectroscopy to identify amino acid-hexose conjugates in the blood plasma from patients with metabolic disorders such as phenylketonuria (PKU). These conjugates, or Amadori rearrangement products, are generally not detectable in blood samples from unaffected individuals, and may therefore represent disease biomarkers. [ABSTRACT FROM AUTHOR]

Infrared multiple photon dissociation (IRMPD) spectroscopy experiments in the 600–2000 cm−1 region and computational chemistry studies were combined with the aim of elucidating the structures of protonated imidacloprid (pIMI), and its unimolecular decomposition products. The computed IR spectra for the lowest energy structures for pIMI as well as for protonated desnitrosoimidacloprid, corresponding to the loss of NO radical (pIMI-NO), and protonated imidacloprid urea corresponding to the loss of N2O (pIMIU) were found to reproduce the experimental IRMPD spectrum quite well. The complex IRMPD spectrum for protonated desnitroimidaclpride (pDIMI), resulting from the loss of NO2 radical from pIMI, was explained as a contribution from several computed structures, including those involving simple loss of NO2 radical and some isomerization. However, based on a comparison of the computed IR spectrum for the lowest energy structure of pDIMI and the IRMPD spectrum, it was concluded that the lowest energy structure is a minor contributor to the experimental spectrum. This observation is rationalized as being due to the energy requirement for isomerization to the lowest energy structure, being substantially higher than that for simple loss of NO2 radical. Experimental mass spectrometry fragmentation results indicated that the loss of N, O2, H was the result of a loss of NO radical followed by loss of OH radical. A comparison of the experimental IRMPD and computed IR spectra revealed that following NO radical loss, the structure entailing a hydride shift from the methylene bridge to the guanidine moiety followed by OH radical elimination, generated the best match with the experimental IRMPD spectrum. This was consistent with the computed potential energy surfaces showing this structure as having the lowest energy requirement. [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]

Migrants have the power to make international law as norm creators. The nation-state enjoys a monopoly on violence in domestic jurisgenesis, but international law's constraint on the use of force provides non-state actors the opportunity to participate in the formation of international legal doctrine without the threat of violence. Scholars have overlooked this nonstate jurisgenerative potential, bound by a state-centric conception of law. This Article applies the claim that non-state actors have the power to influence international law to the transnational issue of climate-induced migration. Climate change intensifies slow- and sudden-onset events, and sudden-onset disasters already displace millions annually. Yet international law grants nation-states the right to largely exclude foreigners such that climate migrants have no right to enter another country, resettle, or be protected against forcible return when they are displaced across borders. While liberal scholars defend this right to exclude as necessary for the preservation of sovereignty, the majority of nation-states participate in free movement agreements--regional trade agreements that promote migration--demonstrating that sovereignty and exclusion are not mutually constitutive. Ultimately, I leverage the challenge of climate-induced migration to ask who has the power to change international law. My response proceeds in two parts. First, the Article challenges the state-centric focus of international law to call attention to non-state actors' ability to create legal norms. Second, I draw on diasporic theory to argue that the Global South diaspora--Global Southerners living in the Global North--should leverage their hybrid positionality to create legal norms that reconstitute sovereignty through admission. International migration theorists reproduce the paradigmatic image of a Global North and Global South border contest, and foreclose the possibility of migrant's jurisgenerative capacity. This Article intentionally shifts the frame to highlight the power that a territorially-unbounded Global South people have to shape international legal norms. [ABSTRACT FROM AUTHOR]

The product of a revealed transformation—NHC‐ethynyl coupling—was observed as a catalyst transformation pathway in the Sonogashira cross‐coupling, catalyzed by Pd/NHC complexes. The 2‐ethynylated azolium salt was isolated in individual form and fully characterized, including X‐ray analysis. A number of possible intermediates of this transformation with common formulae (NHC)nPd(C2Ph) (n=1,2) were observed and subjected to collision‐induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) experiments to elucidate their structure. Measured bond dissociation energies (BDEs) and IRMPD spectra were in an excellent agreement with quantum calculations for coupling product π‐complexes with Pd0. Molecular dynamics simulations confirmed the observed multiple CID fragmentation pathways. An unconventional methodology to study catalyst evolution suggests the reported transformation to be considered in the development of new catalytic systems for alkyne functionalization reactions. [ABSTRACT FROM AUTHOR]

Long-range electron transfer in proteins can be rationalized as a sequential short-distance electron-hopping processes via amino acid residues having low ionization energy as relay stations. Tyrosine residues can serve as such redox-active intermediates through one-electron oxidation to form a π-radical cation at its phenol side chain. An electron transfer from a vicinal functional group to this π-electron hole completes an elementary step of charge migration. However, transient oxidized/reduced intermediates formed at those relay stations during electron transfer processes have not been observed. In this study, formation of analog reactive intermediates via electron donor–acceptor coupling is observed by using IRMPD action spectroscopy. An elementary charge migration at the molecular level in model tyrosine-containing peptide radical cations [M]˙+ in the gas phase is revealed with its unusual Cα–Cβ bond cleavage at the side chain of the N-terminal residue. This reaction is induced by the radical character of the N-terminal amino group (–NH2˙+) resulting from an n → π+ interaction between the nonbonding electron pair of NH2 (n) and the π-electron hole at the Tyr side chain (π+). The formation of –NH2˙+ is supported by the IRMPD spectrum showing a characteristic NH2 scissor vibration coupled with Tyr side-chain stretches at 1577 cm−1. This n → π+ interaction facilitates a dissociative electron transfer with NH2 as the relay station. The occurrence of this side-chain cleavage may be an indicator of the formation of reactive conformers featuring the n → π+ interaction. [ABSTRACT FROM AUTHOR]

The macrocycle valinomycin displays an outstanding ability in cation binding and carriage across hydrophobic environments (e.g., cell membranes) and constitutes a central landmark for the design of novel ionophores for the regulation of biochemical processes. Most previous investigations have focused on the capture of metal cations (primarily K+). Here, we address the versatility of valinomycin in the encapsulation of molecular ions of small and moderate size, with NH4+ and H4PO4+ as case studies. A combination of infrared action vibrational spectroscopy and quantum chemical computations of molecular structure and dynamics is employed with the two-fold aim of assessing the dominant H-bonding coordination networks in the complexes and of characterizing the positional and rotational freedom of the guest cations inside the cavity of the macrocycle. Valinomycin binds NH4+ with only moderate distortion of the C3 configuration adopted in the complexes with the metal cations. The ammonium cation occupies the center of the cavity and displays two low-energy coordination arrangements that are dynamically connected through a facile rotation of the cation. The inclusion of the bulkier phosphoric acid cation demands significant stretching of the valinomycin backbone. Interestingly, the H4PO4+ cation achieves ample positional and rotational mobility inside valinomycin. The valinomycin backbone is capable of adopting barrel-like configurations when the cation occupies a region close to the center of the cavity, and funnel-like configurations when it diffuses to positions close to the exit face. This can accommodate the cation in varying coordination arrangements, characterized by different H-bonding between the four POH arms and the ester carbonyl groups of the macrocycle. [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]

Rationale: Methods for isomer discrimination by mass spectroscopy are of increasing interest. Here we describe the development of a three‐dimensional ion trap for infrared multiple photon dissociation (IRMPD) spectroscopy that enables the acquisition of the infrared spectrum of selected ions in the gas phase. This system is suitable for the study of a myriad of chemical systems, including isomer mixtures. Methods: A modified three‐dimensional ion trap was coupled to a CO2 laser and an optical parametric oscillator/optical parametric amplifier (OPO/OPA) system operating in the range 2300 to 4000 cm−1. Density functional theory vibrational frequency calculations were carried out to support spectral assignments. Results: Detailed descriptions of the interface between the laser and the mass spectrometer, the hardware to control the laser systems, the automated system for IRMPD spectrum acquisition and data management are presented. The optimization of the crystal position of the OPO/OPA system to maximize the spectroscopic response under low‐power laser radiation is also discussed. Conclusions: OPO/OPA and CO2 laser‐assisted dissociation of gas‐phase ions was successfully achieved. The system was validated by acquiring the IRMPD spectra of model species and comparing with literature data. Two isomeric alkaloids of high economic importance were characterized to demonstrate the potential of this technique, which is now available as an open IRMPD spectroscopy facility in Brazil. [ABSTRACT FROM AUTHOR]

Solar energy is one of the main renewable energy sources currently being researched, with commercial thin film solar cells currently made of CdTe or CuIn(1−x)GaxSe2 (CIGS) absorbers. However, whilst these materials make up the majority of the thin film commercial market, these solar cells have various problems relating to materials cost, and toxicity of constituent elements. Kesterite (Cu2ZnSn(S,Se)4) solar cells are becoming increasingly popular due to their tuneable band gap, relative affordability of the constituent elements, and the ability to produce high efficiency devices from solution processes. However, often expensive and toxic materials are used in production. In this paper we report on a newly developed amine–thiol solvent system based on 10% cysteamine in ethanolamine, which has low toxicity, is user-friendly and is able to readily dissolve all kesterite constituent elements, including metals and their oxides. The dissolution process and the structures of the prevalent metal complexes formed were investigated with the aid of spectroscopic methods, such as electrospray ionization mass spectrometry (ESI-MS) and infrared multiple photon dissociation (IRMPD). In most cases, two molecules of cysteamine were bound to the metals as bidentate ligands. By employing spin coating of the resulting inks, devices of up to 8.1% power conversion efficiency were fabricated. [ABSTRACT FROM AUTHOR]

Microspheres containing radioactive 166holmium-acetylacetonate are employed in emerging radionuclide therapies for the treatment of malignancies. At the molecular level, details on the coordination geometries of the Ho complexes are however elusive. Infrared ion spectroscopy (IRIS) was used to characterize several 165Ho-acetylacetonate complexes derived from non-radioactive microspheres. The coordination geometry of four distinct ionic complexes were fully assigned by comparison of their measured IR spectra with spectra calculated at the density functional theory (DFT) level. The coordination of each acetylacetonate ligand is dependent on the presence of other ligands, revealing an asymmetric chelation motif in some of the complexes. A fifth, previously unknown constituent of the microspheres was identified as a coordination complex containing an acetic acid ligand. These results pave the way for IRIS-based identification of microsphere constituents upon neutron activation of the metal center. [ABSTRACT FROM AUTHOR]

We report herein the first detailed study of the mechanism of redox reactions occurring during the gas-phase dissociative electron transfer of prototypical ternary [CuII(dien)M]˙2+ complexes (M, peptide). The two final products are (i) the oxidized non-zwitterionic π-centered [M]˙+ species with both the charge and spin densities delocalized over the indole ring of the tryptophan residue and with a C-terminal COOH group intact, and (ii) the complementary ion [CuI(dien)]+. Infrared multiple photon dissociation (IRMPD) action spectroscopy and low-energy collision-induced dissociation (CID) experiments, in conjunction with density functional theory (DFT) calculations, revealed the structural details of the mass-isolated precursor and product cations. Our experimental and theoretical results indicate that the doubly positively charged precursor [CuII(dien)M]˙2+ features electrostatic coordination through the anionic carboxylate end of the zwitterionic M moiety. An additional interaction exists between the indole ring of the tryptophan residue and one of the primary amino groups of the dien ligand; the DFT calculations provided the structures of the precursor ion, intermediates, and products, and enabled us to keep track of the locations of the charge and unpaired electron. The dissociative one-electron transfer reaction is initiated by a gradual transition of the M tripeptide from the zwitterionic form in [CuII(dien)M]˙2+ to the non-zwitterionic M intermediate, through a cascade of conformational changes and proton transfers. In the next step, the highest energy intermediate is formed; here, the copper center is 5-coordinate with coordination from both the carboxylic acid group and the indole ring. A subsequent switch back to 4-coordination to an intermediate IM1, where attachment to GGW occurs through the indole ring only, creates the structure that ultimately undergoes dissociation. [ABSTRACT FROM AUTHOR]

Controlling the chemical glycosylation reaction remains the major challenge in the synthesis of oligosaccharides. Though 1,2-trans glycosidic linkages can be installed using neighboring group participation, the construction of 1,2-cis linkages is difficult and has no general solution. Long-range participation (LRP) by distal acyl groups may steer the stereoselectivity, but contradictory results have been reported on the role and strength of this stereoelectronic effect. It has been exceedingly difficult to study the bridging dioxolenium ion intermediates because of their high reactivity and fleeting nature. Here we report an integrated approach, using infrared ion spectroscopy, DFT computations, and a systematic series of glycosylation reactions to probe these ions in detail. Our study reveals how distal acyl groups can play a decisive role in shaping the stereochemical outcome of a glycosylation reaction, and opens new avenues to exploit these species in the assembly of oligosaccharides and glycoconjugates to fuel biological research. Dioxolenium ion intermediates formed from remote positions are hypothesized to direct stereoselective glycosylations. Herein we combine infrared ion spectroscopy, DFT calculations and synthetic work to characterize and study these dioxolenium ions and their role in stereoselective glycosylation reactions. [ABSTRACT FROM AUTHOR]

The structures and properties of metal cationized complexes of 9-ethylguanine (9eG) and 1-methylcytosine (1mC), (9eG:1mC)M+, where M+ = Li+, Na+, K+, Rb+, Cs+ as well as the protonated complex, (9eG:1mC)H+, have been studied using a combination of IRMPD spectroscopy and computational methods. For (9eG:1mC)H+, the dominant structure is a Hoogsteen type complex with the proton covalently bound to N3 of 1mC despite this being the third best protonation site of the two bases; based on proton affinities N7 of 9eG should be protonated. However, this structural oddity can be explained considering both the number of hydrogen bonds that can be formed when N3 of 1mC is protonated as well as the strong ion-induced dipole interaction that exists between an N3 protonated 1mC and 9eG due to the higher polarizability of 9eG. The anomalous dissociation of (9eG:1mC)H+, forming much more (1mC)H+ than would be predicted based on the computed thermochemistry, can be explained as being due to the structural oddity of the protonation site and that the barrier to proton transfer from N3 of 1mC to N7 of 9eG grows dramatically as the base pair begins to dissociate. For the (9eG:1mC)M+; M = Li+, Na+, K+, Rb+, Cs+ complexes, single unique structures could not be assigned. However, the experimental spectra were consistent with the computed spectra. For (9eG:1mC)Li+, the lowest energy structure is one in which Li+ is bound to O6 of 9eG and both O2 and N3 of 1mC; there is also an interbase hydrogen bond from the amine of 1mC to N7 of 9eG. For Na+, K+, and Rb+, similar binding of the metal cation to 1mC is calculated but, unlike Li+, the lowest energy structure is one in which the metal cation is bound to N7 of 9eG; there is also an interbase hydrogen bond between the amine of 1mC and the carbonyl of 9eG. The lowest energy structure for the Cs complex is the Watson–Crick type base pairing with Cs+ binding only to 9eG through O6 and N7 and with three hydrogen bonds between 9eG and 1mC. It also interesting to note that the Watson–Crick base pairing structure gets lower in Gibbs energy relative to the lowest energy complexes as the metal gets larger. This indicates that the smaller, more densely charged cations have a greater propensity to interfere with Watson–Crick base pairing than do the larger, less densely charged metal cations. [ABSTRACT FROM AUTHOR]

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]

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]