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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 the DFT calculated spectra with the experimentally observed IR spectra provided valuable insights in the conformations of the N -acyliminium ions.

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., Breslow intermediates in the gas phase: In N‐heterocyclic carbene (NHC)‐catalyzed Umpolung, the reaction of the substrate aldehyde with the NHC gives the Breslow intermediate (BI) as pivotal species. The combination of IR ion spectroscopy with quantum chemical computations can determine whether the BI exists as a nucleophilic amino enol or as its keto tautomer in the gas phase, which is decisive for its reactivity both in enzymatic catalysis and in organocatalysis.

The capability of an ion trap mass spectrometer to store ions for an arbitrary amount of time allows the use of a single infrared (IR) laser to perform two-color double resonance IR–IR spectroscopic experiments on mass-to-charge (m/z) selected ions. In this single-laser IR2MS3 scheme, one IR laser frequency is used to remove a selected set of isomers from the total trapped ion population and the second IR laser frequency, from the same laser, is used to record the IR spectrum of the remaining precursor ions. This yields isomer-specific vibrational spectra of the m/z-selected ions, which can reveal the structure and identity of the initially co-isolated isomeric species. The use of a single laser greatly reduces the experimental complexity of two-color IR2MS3 and enhances its application in fields employing analytical MS. In this work, we demonstrate the methodology by acquiring single-laser IR2MS3 spectra in a forensic context, identifying two previously unidentified isomeric novel psychoactive substances (NPS) from a sample that was confiscated by the Amsterdam Police.

Deamidation of asparaginyl (Asn) peptides is a spontaneous post-translational modification that plays a significant role in degenerative diseases and other biological processes under physiological conditions. In the gas phase, deamidation of protonated peptides is a major fragmentation channel upon activation by collision-induced dissociation. Here, we present a full description of the deamidation process from protonated asparagine-serine, [AsnSer+H]+, -via infrared (IR) action spectroscopy and threshold collision-induced dissociation (TCID) experiments in combination with theoretical calculations. The IR results demonstrate that deamidation proceeds via bifurcating reaction pathways leading to furanone- and succinimide-type product ion structures, with a population analysis indicating the latter product dominates. Theory demonstrates that nucleophilic attack of the peptidyl amide oxygen onto the Asn side chain leads to furanone formation, whereas nudeophilic attack by the peptidyl amide nitrogen onto the Asn side-chain carbonyl carbon leads to the formation of the succinimide product structure. TCID experiments find that furanone formation has a threshold energy of 145 +/- 12 kJ/mol and succinimide formation occurs with a threshold energy of 131 +/- 12 kJ/mol, consistent with theoretical energies and with the spectroscopic results indicating that succinimide dominates. The results provide information regarding the inductive and steric effects of the Ser side chain on the deamidation process. The other major channel observed in the TCID experiments of [AsnSer+H]+ is dehydration, where a threshold energy of 104 +/- 10 kJ/mol is determined. A complete IR and theoretical analysis of this pathway is also provided. As for deamidation, a bifurcating pathway is found with both dominant oxazoline and minor diketopiperazine products identified. Here, the Ser side chain is directly involved in both pathways.

Untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics strategies are being increasingly applied in metabolite screening for a wide variety of medical conditions. The long-standing "grand challenge" in the utilization of this approach is metabolite identification-confidently determining the chemical structures of m/z-detected unknowns. Here, we use a novel workflow based on the detection of molecular features of interest by high-throughput untargeted LC-MS analysis of patient body fluids combined with targeted molecular identification of those features using infrared ion spectroscopy (IRIS), effectively providing diagnostic IR fingerprints for mass-isolated targets. A significant advantage of this approach is that in silico-predicted IR spectra of candidate chemical structures can be used to suggest the molecular structure of unknown features, thus mitigating the need for the synthesis of a broad range of physical reference standards. Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an inborn error of lysine metabolism, resulting from a mutation in the ALDH7A1 gene that leads to an accumulation of toxic levels of alpha-aminoadipic semialdehyde (alpha-AASA), piperideine-6-carboxylate (P6C), and pipecolic acid in body fluids. While alpha-AASA and P6C are known biomarkers for PDE in urine, their instability makes them poor candidates for diagnostic analysis from blood, which would be required for application in newborn screening protocols. Here, we use combined untargeted metabolomics-IRIS to identify several new biomarkers for PDE-ALDH7A1 that can be used for diagnostic analysis in urine, plasma, and cerebrospinal fluids and that are compatible with analysis in dried blood spots for newborn screening. The identification of these novel metabolites has directly provided novel insights into the pathophysiology of PDE-ALDH7A1.

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)n Pd(C2 Ph) (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.

Experimental IR spectra in the 500-1850 cm-1 fingerprint frequency range are presented for the isolated, gaseous redox pair ions [Ru(bpy)3]2+, and [Ru(bpy)3]+, where bpy = 2,2'-bipyridine. Spectra are obtained using the FELIX free-electron laser and a quadrupole ion trap mass spectrometer. The 2+ complex is generated by electrospray ionization and the charge-reduced radical cation is produced by gas-phase one-electron reduction in an ion-ion reaction with the fluoranthene radical anion. Experimental spectra are compared against computed spectra predicted by density functional theory (DFT) using different levels of theory. For the closed-shell [Ru(bpy)3]2+ ion, the match between experimental and computed IR spectra is very good; however, this is not the case for the charge-reduced [Ru(bpy)3]+ ion, which demands additional theoretical investigation. When using the hybrid B3LYP functional, we observe that better agreement with experiment is obtained upon reduction of the Hartree-Fock exact-exchange contribution from 204 calculations using the M06 functional appear to be promising in terms of the prediction of IR spectra; however, it is unclear if the correct electronic structure is obtained. The M06 and B3LYP functionals indicate that the added electron in [Ru(bpy)3)]+ is delocalized over the three bpy ligands, while the long-range corrected LC-BLYP and the CAM-B3LYP functionals show it to be more localized on a single bpy ligand. Although these latter levels of theory fail to reproduce the experimentally observed IR frequencies, one may argue that the unusually large bandwidths observed in the spectrum are due to the fluxional character of a complex with the added electron not symmetrically distributed over the ligands. The experimental IR spectra presented here can serve as benchmark for further theoretical investigations.

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. Here, we demonstrate infrared ion spectroscopy (IRIS) as a promising new mass spectrometry-based technique that easily differentiates between positional isomers of disubstituted phenyl-containing compounds. By analyzing different substitution patterns over several sets of isomeric compounds, we show that IRIS produces a highly consistent and distinct pattern of IR bands, especially in the range between 650 and 900 cm-1, that are mostly independent of the specific chemical functionality contained in the substituent group. These patterns are accurately predicted by quantum-chemically computed IR spectra and correspond well with tabulated IR group-frequencies known from conventional absorption spectroscopy. Therefore, we foresee that this method will be generally applicable to disubstituted phenyl-containing compounds and that direct interpretation of experimental IRIS spectra in terms of ortho-, meta- or para-substitution is possible, even without comparison to experimental or computationally predicted reference spectra. Strategies for the analysis of larger compounds having more congested IR spectra as well as of compounds having low (electrospray) ionization efficiencies are presented in order to demonstrate the broad applicability of this methodology.

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.

Infrared multiple photon dissociation action spectroscopy was performed on the AlaOrn b(2)(+) and AlaAlaOrn b(3)(+) fragment ions from ornithine-containing tetrapeptides. Infrared spectra were obtained in the fingerprint region (1000 – 2000 cm(−1)) using the infrared free electron lasers at the Centre Laser Infrarouge d’Orsay (CLIO) facility in Orsay, France and the Free Electron Lasers for Infrared eXperiments (FELIX) facility in Nijmegen, the Netherlands. A novel terminal ornithine lactam AO(+) b2(+) structure was synthesized for experimental comparison and spectroscopy confirms that the b2(+) fragment ion from AOAA forms a lactam structure. Comparison of experimental spectra with scaled harmonic frequencies at the B3LYP/6-31+G(d,p) level of theory shows that AO(+) b(2)(+) forms a terminal lactam protonated either on the lactam carbonyl oxygen or the N-terminal nitrogen atom. Several low-lying conformers of these isomers are likely populated following IRMPD dissociation. Similarly, a comparison of the experimental IRMPD spectrum with calculated spectra shows that AAO(+) b(3)(+)-ions also adopt a lactam structure, again with multiple different protonation sites, during fragmentation. This study provides spectroscopic confirmation for the lactam cyclization proposed for the “ornithine effect” and represents an alternative b(n)(+) structure to the oxazolone and diketopiperazine/macrocycle structures most often formed.

Uronic acids are important constituents of polysaccharides found on the cell membranes of different organisms. To prepare uronic-acid-containing oligosaccharides, uronic acid 6,3-lactones can be employed as they display a fixed conformation and a unique reactivity and stereoselectivity. Herein, we report a highly β-selective and efficient mannosyl donor based on C-4 acetyl mannuronic acid 6,3-lactone donors. The mechanism of glycosylation is established using a combination of techniques, including infrared ion spectroscopy combined with quantum-chemical calculations and variable-temperature nuclear magnetic resonance (VT NMR) spectroscopy. The role of these intermediates in glycosylation is assayed by varying the activation protocol and acceptor nucleophilicity. The observed trends are analogous to the well-studied 4,6-benzylidene glycosides and may be used to guide the development of next-generation stereoselective glycosyl donors.

Electrospray ionization was used to generate species such as [ZnNO3(CH3OH)2]+ from Zn(NO3)2•XH2O dissolved in a mixture of CH3OH and H2O. Collision-induced dissociation of [ZnNO3(CH3OH)2]+ causes elimination of CH3OH to form [ZnNO3(CH3OH)]+. Subsequent collision-induced dissociation of [ZnNO3(CH3OH)]+ causes elimination of 47 mass units (u), consistent with ejection of HNO2. The neutral loss shifts to 48 u for collision-induced dissociation of [ZnNO3(CD3OH)]+, demonstrating the ejection of HNO2 involves intra-complex transfer of H from the methyl group methanol ligand. Subsequent collision-induced dissociation causes the elimination of 30 u (32 u for the complex with CD3OH), suggesting the elimination of formaldehyde (CH2 = O). The product ion is [ZnOH]+. Collision-induced dissociation of a precursor complex created using CH3-18OH shows the isotope label is retained in CH2 = O. Density functional theory calculations suggested that the “rearranged” product, ZnOH with bound HNO2 and formaldehyde is significantly lower in energy than ZnNO3 with bound methanol. We therefore used infrared multiple-photon photodissociation spectroscopy to determine the structures of both [ZnNO3(CH3OH)2]+ and [ZnNO3(CH3OH)]+. The infrared spectra clearly show that both ions contain intact nitrate and methanol ligands, which suggests that rearrangement occurs during collision-induced dissociation of [ZnNO3(CH3OH)]+. Based on the density functional theory calculations, we propose that transfer of H, from the methyl group of the CH3OH ligand to nitrate, occurs in concert with the formation of a Zn–C bond. After dissociation to release HNO2, the product rearranges with the insertion of the remaining O atom into the Zn–C bond. Subsequent C–O bond cleavage, with H transfer, produces an ion–molecule complex composed of [ZnOH]+ and O = CH2.

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.

Uranium trioxide, UO3, has a T-shaped structure with bent uranyl, UO22+, coordinated by an equatorial oxo, O2-. The structure of cation UO3+ is similar but with an equatorial oxyl, O center dot-. Neutral and cationic uranium trioxide coordinated by nitrates were characterized by collision induced dissociation (CID), infrared multiple-photon dissociation (IRMPD) spectroscopy, and density functional theory. CID of uranyl nitrate, [UO2 (NO3)3]- (complex A1), eliminates NO2 to produce nitrate-coordinated UO3+, [UO2 (O. )(NO3)2]-(B1), which ejects NO3 to yield UO3 in [UO2 (O)(NO3)]- (C1). Finally, C1 associates with H2O to afford uranyl hydroxide in [UO2(OH)2 (NO3)]- (D1). IRMPD of B1, C1, and D1 confirms uranyl equatorially coordinated by nitrate(s) along with the following ligands: (B1) radical oxyl O.-; (C1) oxo O2-; and (D1) two hydroxyls, OH- . As the nitrates are bidentate, the equatorial coordination is six in A1, five in B1, four in D1, and three in C1. Ligand congestion in low-coordinate C1 suggests orbital-directed bonding. Hydrolysis of the equatorial oxo in C1 epitomizes the inverse trans influence in UO3, which is uranyl with inert axial oxos and a reactive equatorial oxo. The uranyl v3 IR frequencies indicate the following donor ordering: O2- [best donor] >> O.- > OH-> NO3-.

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.

With the detection of C60, C70, and in the interstellar medium, fullerenes are currently the largest molecules identified in space. The relatively high proton affinities of C60 and C70 support the hypothesis that protonated fullerenes may also be abundant in the interstellar matter. Here, we present the first experimental vibrational spectrum of C70H+, recorded in the gas phase. The attachment of a proton to C70 causes a drastic symmetry lowering, which results in a rich vibrational spectrum. As compared to C60, where all C-atoms are equivalent due to the icosahedral symmetry, C70 belongs to the D5h point group and has five nonequivalent C-atoms, which are available as protonation sites. Combined analysis of the experimental spectrum and spectra computed at the density functional theory level enables us to evaluate the protonation isomers being formed. We compare the IR spectra of C60H+ and C70H+ to IR emission spectra from planetary nebulae, which suggests that a mixture of these fullerene analogs could contribute to their IR emission.

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.

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.

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.

Infrared multiple photon dissociation (IRMPD) spectroscopy shows the [GPGG + H – H2O]+ ion to have an imidazolone structure. Collision-induced dissociation of this [b4]+ ion results in the loss of HN CH2 from the first residue; the IRMPD spectrum of this MS3 product ion is very similar to that of the [b4]+ ion itself, strongly indicating that the [b4 – HN CH2]+ ion also has an imidazolone structure. Losses of CO and glycine are the dominant dissociation pathways for the [b4 – HN CH2]+ ion. The latter loss requires tautomerism of the keto-form of the imidazolone ring to become the lower-energy enol-form, prior to dissociation. Isotopic labelling showed that loss of CO occurs from the ring of the keto-form. Density functional theory calculations were performed at both the B3LYP/6–311++G (d,p) and M06–2X/6–311++G (d,p) levels and the results are in good agreement.

The molecular structures of six open-shell z3-ions resulting from electron transfer dissociation mass spectrometry (ETD MS) were investigated using infrared ion spectroscopy in the 800–1850 and 3200–3700 cm−1 spectral ranges in combination with density functional theory and molecular mechanics/molecular dynamics calculations. We assess in particular the question of whether the radical remains at the Cα-site of the backbone cleavage, or whether it migrates by H-atom transfer to another, energetically more favorable position. Calculations performed herein as well as by others show that radical migration to an amino acid side chain or to an α-carbon along the peptide backbone can lead to structures that are more stable, by up to 33 kJ mol−1 for the systems investigated here, by virtue of resonance stabilization of the radical in these alternative positions. Nonetheless, for four out of the six z3-ions considered here, our results quite clearly indicate that radical migration does not occur, suggesting that the radical is kinetically trapped at the site of ETD cleavage. For the two remaining systems, a structural assignment is less secure and we suggest that a mixture of migrated and unmigrated structures may be formed.

The molecular family of nucleotide triphosphates (NTPs), with adenosine 5′-triphosphate (ATP) as its best-known member, is of high biochemical importance as their phosphodiester bonds form Nature's main means to store and transport energy. Here, gas-phase IR spectroscopic studies and supporting theoretical studies have been performed on adenosine 5′-triphosphate, cytosine 5′-triphosphate and guanosine 5′-triphosphate to elucidate the intrinsic structural properties of NTPs, focusing on the influence of the nucleobase and the extent of deprotonation. Mass spectrometric studies involving collision induced dissociation showed similar fragmentation channels for the three studied NTPs within a selected charge state. The doubly charged anions exhibit fragmentation similar to the energy-releasing hydrolysis reaction in nature, while the singly charged anions show different dominant fragmentation channels, suggesting that the charge state plays a significant role in the favorability of the hydrolysis reaction. A combination of infrared ion spectroscopy and quantum-chemical computations indicates that the singly charged anions of all NTPs are preferentially deprotonated at their β-phosphates, while the doubly-charged anions are dominantly αβ-deprotonated. The assigned three-dimensional structure differs for ATP and CTP on the one hand and GTP on the other, in the sense that ATP and CTP show no interaction between nucleobase and phosphate tail, while in GTP they are hydrogen bonded. This can be rationalized by considering the structure and geometry of the NTPs where the final three dimensional structure depends on a subtle balance between hydrogen bond strength, flexibility and steric hindrance.

Synthesis and spectra of isocytosino-8-trifluoromethylquinolone (1), as well as the gas phase InfraRed Multiple Photon Dissociation (IRMPD) spectra in the fingerprint region of the corresponding deprotonated anion (3), its d3 analogue, the monodeprotonated homodimer (2), and its d7 analogue are reported here. The anions represent nucleobase analogues having the hydrogen bonding pattern ADAAD (where A stands for acceptor and D stands for donor), in which the site of negative charge is unambiguous (as opposed to guanine, which has more than one acidic nitrogen). The match between experimental vibrational spectra and calculation is good, except for the out-of-plane HNH bends of the undeuterated and deuterated monomer anions between 400 and 600 cm−1. The anionic homodimers form in a parallel orientation.

The role of specific amino acid side-chains in the fragmentation chemistry of gaseous protonated peptides resulting from collisional activation remains incompletely understood. For small peptides containing asparagine and glutamine, a dominant fragmentation channel induced by collisional activations is, in addition to deamidation, the loss of neutral water. Identifying the product ion structures from H2O-loss from four protonated dipeptides containing Asn or Gln using infrared ion spectroscopy, mechanistic details of the dissociation reactions are revealed. Several sequential dissociation reactions have also been investigated and provide additional insights into the fragmentation chemistry. While water loss can in principle occur from the C-terminus, the side chain or the amide bond carbonyl oxygen, in most cases the C-terminus was found to detach H2O, leading to a b2-sequence ion with an oxazolone structure for AlaGln, and bifurcating mechanisms leading to both oxazolone and diketopiperazine species for AlaAsn and AsnAla. In contrast, GlnAla expels water from the amide side chain leading to an imino-substituted prolinyl structure.

Complexes of divalent metal ions (Cu2+ and Ni2+) with histidine tripeptide complexes (HAA, AHA and AAH) are interesting gas-phase models for some of the most widely observed patterns of metal ion binding to peptides and proteins. Gas-phase structures were characterized using infrared multiple photon dissociation (IRMPD) spectroscopy in ion-trapping mass spectrometers, along with density functional theory (DFT) computations. Ground states are square-planar with two deprotonated amide nitrogens bound to the metal ion via a double iminol rearrangement (IM binding mode), but contrary to expectations based on solution behavior, the histidine imidazole group is not bound to the metal, but instead is hydrogen bonded remote from the metal ion. The alternative “charge-solvated” (CS) binding mode (amide carbonyl oxygens binding the metal ion) lies higher in energy, but in many cases was observed to be present as conformationally unrelaxed ions with an abundance (relative to the IM conformation) that was dependent on instrument configuration and source and trap conditions. Taking advantage of the ability to form and trap both IM and CS conformations for a few of the complexes, the infrared spectroscopy of both conformations was explored in the fingerprint (1000–1800 cm−1) and hydrogen-stretching (3200–3800 cm−1) regions. For the fingerprint region, agreement is very good between the observed IRMPD spectra and the spectra predicted by DFT calculations at the B3LYP/6–311 + +g(d,p) level. Agreement in the H-stretching region is not perfect, but the characteristic IM and CS spectral patterns are evident.

The identification of molecular biomarkers is critical for diagnosing and treating patients and for establishing a fundamental understanding of the pathophysiology and underlying biochemistry of inborn errors of metabolism. Currently, liquid chromatography/high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy are the principle methods used for biomarker research and for structural elucidation of small molecules in patient body fluids. While both are powerful techniques, several limitations exist that often make the identification of unknown compounds challenging. Here, we describe how infrared ion spectroscopy has the potential to be a valuable orthogonal technique that provides highly-specific molecular structure information while maintaining ultra-high sensitivity. Here, we characterize and distinguish two well-known biomarkers of inborn errors of metabolism, glutaric acid for glutaric aciduria and ethylmalonic acid for short-chain acyl-CoA dehydrogenase deficiency, using infrared ion spectroscopy. In contrast to tandem mass spectra, in which ion fragments can hardly be predicted, we show that the prediction of an IR spectrum allows reference-free identification in the case that standard compounds are either commercially or synthetically unavailable. Finally, we illustrate how functional group information can be obtained from an IR spectrum for an unknown and how this is valuable information to, for example, narrow down a list of candidate structures resulting from a database query. Early diagnosis in inborn errors of metabolism is crucial for enabling treatment and depends on the identification of biomarkers specific for the disorder. Infrared ion spectroscopy has the potential to play a pivotal role in the identification of challenging biomarkers.

International audience; Dissociation chemistry of the diproline anion [Pro2-H]− is studied using chemical dynamics simulations coupled with quantum-chemical calculations and RRKM analysis. Pro2– is chosen due to its reduced size and the small number of sites where deprotonation can take place. The mechanisms leading to the two dominant collision-induced dissociation (CID) product ions are elucidated. Trajectories from a variety of isomers of [Pro2-H]− were followed in order to sample a larger range of possible reactivity. While different mechanisms yielding y1– product ions are proposed, there is only one mechanism yielding the b2– ion. This mechanism leads to formation of a b2– fragment with a diketopiperazine structure. The sole formation of a diketopiperazine b2 sequence ion is experimentally confirmed by infrared ion spectroscopy of the fragment anion. Furthermore, collisional and internal energy activation simulations are used in parallel to identify the different dynamical aspects of the observed reactivity.

The following gas-phase uranyl/12-crown-4 (12C4) complexes were synthesized by electrospray ionization: [UO2(12C4)2]2+ and [UO2(12C4)2(OH)]+. Collision-induced dissociation (CID) of the dication resulted in [UO2(12C4-H)]+ (12C4-H is a 12C4 that has lost one H), which spontaneously adds water to yield [UO2(12C4-H)(H2O)]+. The latter has the same composition as complex [UO2(12C4)(OH)]+ produced by CID of [UO2(12C4)2(OH)]+ but exhibits different reactivity with water. The postulated structures as isomeric [UO2(12C4-H)(H2O)]+ and [UO2(12C4)(OH)]+ were confirmed by comparison of infrared multiphoton dissociation (IRMPD) spectra with computed spectra. The structure of [UO2(12C4-H)]+ corresponds to cleavage of a C–O bond in the 12C4 ring, with formation of a discrete U–Oeq bond and equatorial coordination by three intact ether moieties. Comparison of IRMPD and computed IR spectra furthermore enabled assignment of the structures of the other complexes. Theoretical studies of the chemical bonding features of the complexes provide an understanding of their stabilities and reactivities. The results reveal bonding and structures of the uranyl/12C4 complexes and demonstrate the synthesis and identification of two different isomers of gas-phase uranyl coordination complexes.

Infrared multiple photon dissociation spectroscopy was performed on protonated and cationized canavanine (Cav), a non-protein amino acid oxy-analog of arginine. Infrared spectra in the XH stretching region (3000–4000 cm−1) were obtained at the Centre Laser Infrarouge d’Orsay (CLIO) facility. Comparison of the experimental infrared spectra with scaled harmonic frequencies at the B3LYP/6-31+G(d,p) level of theory indicates that canavanine is in a canonical neutral form in CavH+, CavLi+, and CavNa+; therefore, these cations are charge-solvated structures. The infrared spectrum of CavK+ is consistent with a mixture of Cav in canonical and zwitterionic forms leading to both charge-solvated and salt-bridged cationic structures. The Cav moiety in CavCs+ is shown to be zwitterionic, forming a salt-bridged structure for the cation. Infrared spectra in the fingerprint region (1000–2000 cm−1) obtained at the FELIX Laboratory in Nijmegen, Netherlands support these assignments. These results show that a single oxygen atom substitution in the side chain reduces the stability of the zwitterion compared to that of the protein amino acid arginine (Arg), which has been shown previously to adopt a zwitterionic structure in ArgNa+ and ArgK+. This difference can be explained in part due to the decreased basicity of Cav (PA = 1001 kJ/mol) as compared to arginine (PA = 1051 kJ/mol), but not entirely, as lysine, which has nearly the same proton affinity as Cav, (∼993 kJ/mol) forms only canonical structures with Na+, K +, and Cs+. A major difference between the zwitterionic forms of ArgM+ and CavM+ is that the protonation site is on the side chain for Arg and on the N-terminus for Cav. This results in systematically weaker salt bridges in the Cav zwitterions. In addition, the presence of another hydrogen-bonding acceptor atom in the side chain contributes to the stability of the canonical structures for the smaller alkali cations.

Electron attachment dissociation (electron capture dissociation (ECD) and electron transfer dissociation (ETD)) applied to gaseous multiply protonated peptides leads predominantly to backbone N–Cα bond cleavages and the formation of c- and z-type fragment ions. The mechanisms involved in the formation of these ions have been the subject of much discussion. Here, we determine the molecular structures of an extensive set of c-type ions produced by ETD using infrared ion spectroscopy. Nine c3- and c4-ions are investigated to establish their C-terminal structure as either enol-imine or amide isomers by comparison of the experimental infrared spectra with quantum-chemically predicted spectra for both structural variants. The spectra suggest that all c-ions investigated possess an amide structure; the absence of the NH bending mode at approximately 1000–1200 cm–1 serves as an important diagnostic feature.

Contains fulltext : 182103.pdf (Publisher’s version ) (Open Access) Evidence is presented for cyclization to yield 2-bora-1,3-diazacycloalkanium cations in the gas phase. While the neutral compounds in solution and solid phase are known to possess an acyclic structure (as revealed by X-ray diffraction), the gaseous cations (from which borohydride BH4(-) ion has been expelled) have a cyclic structure, as revealed by InfraRed Multiple Photon Dissociation (IRMPD) spectroscopy and collisionally activated decomposition (CAD). The IRMPD decomposition of the monocyclic ions proceeds principally via H2 expulsion, although CAD experiments show additional pathways. Pyrolyses of solid monomeric salts and small oligomers produce higher polymers that are consistent with H2 expulsion as the major pathway. Deuterium labeling experiments show that scrambling occurs prior to IRMPD or CAD decomposition in the gas phase.

Ni(II) ions can be caged by surrounding peptide ligands in two basic binding patterns: the “iminol” (IM) binding pattern, where chelation occurs by deprotonated amide nitrogens, or the charge-solvated (CS) binding pattern, where chelation occurs by amide carbonyl oxygens. Gas-phase observation may clarify the factors affecting this choice in solution and in peptide and protein matrices. Infrared spectroscopic determination of gas-phase structures shows here how microsolvation by just one water molecule switches the balance of this choice from IM to CS for the Ni2+Gly3 complex, in contrast with the always-CS structure of the Ni2+Gly4 complex. Quantum-chemical calculations indicate that CS complexation is even more favored in the aqueous limit. Considering gas-phase conditions as comparable to low-pH solutions can reconcile this prediction with the common observation of IM-type binding in solutions at higher pH. This is likely the first gas-phase observation of solvation-induced IM-to-CS transition in oligopeptide complexes with doubly charged transition-metal ions.

In the complex formed between the calcium cation (Ca2+) and a deprotonated HisHis dipeptide, the complex adopts a charge solvation (CS) structure. Ca2+, a weak binding main group metal cation, interacts with the oxygens of the peptide carbonyl moiety and the deprotonated C-terminus. In contrast, the much stronger binding Ni2+ cation deprotonates the peptide nitrogen and induces an iminolate (Im) ligand structure in the [Ni(HisHis-H)]+ complex ion. The combination of infrared multiple-photon dissociation (IRMPD) spectroscopy and quantum chemistry evidence these two representative binding motifs. The iminolate coordination pattern identified and characterized in the [Ni(HisHis-H)]+ complex serves as a model case for nickel complexes of poly-histidyl-domains and is thereby also of interest to better understand the fundamentals of immobilized metal ion affinity chromatography as well as of Ni co-factor chemistry in enzymology.

Infrared multiple photon dissociation (IRMPD) spectroscopy has been used to probe the structures of the three protonated base-pair mismatches containing 9-ethylguanine (9eG) in the gas phase. Computational chemistry has been used to determine the relative energies and compute the infrared spectra of these complexes. By comparing the IRMPD spectra with the computed spectra, in all cases, it was possible to deduce that what was observed experimentally were the lowest energy computed structures. The protonated complex between 9eG and 1-methylthymine (1mT) is protonated at N7 of 9eG—the most basic site of all three bases in this study—and bound in a Hoogsteen type structure with two hydrogen bonds. The experimental IRMPD spectrum for the protonated complex between 9eG and 9-methyladenine (9mA) is described as arising from a combination of the two lowest energy structures, both which are protonated at N1 of adenine and each containing two hydrogen bonds with 9eG being the acceptor of both. The protonated dimer of 9eG is protonated at N7 with an N7–H+–N7 ionic hydrogen bond. It also contains an interaction between a C–H of protonated guanine and the O6 carbonyl of neutral guanine which is manifested in a slight red shift of that carbonyl stretch. The protonated 9eG/9mA structures have been previously identified by X-ray crystallography in RNA and are contained within the protein database.

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.

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.

Hydroxyproline is a common variation of proline, with diverse biological roles. The hydroxylation of proline gives rise to several (natural and/or synthetic) isomeric forms, including both positional isomers and stereoisomers. While mass spectrometry is widely touted as a very selective analytical technique, the identification of closely related isomers often poses a challenge. In these cases, allied technologies become helpful in providing full characterization. Here, infrared multiple photon dissociation (IRMPD) spectroscopy is used to differentiate between three isomers, namely cis-3-hydroxyproline, cis-4-hydroxyproline, and trans-4-hydroxyproline. In contrast to the protonated species which show only minor variations in their IRMPD spectra, lithiated species were found to display significant spectral differences, making their differentiation more straightforward. The conformational origin of these spectral differences was investigated by complementary quantum-chemical calculations.

Infrared ion spectroscopy (IRIS), a mass-spectrometry-based technique exploiting resonant infrared multiple photon dissociation (IRMPD), has been applied for the identification of novel psychoactive substances (NPS). Identification of the precise isomeric forms of NPS is of significant forensic relevance since legal controls are dependent on even minor molecular differences such as a single ring-substituent position. Using three isomers of fluoroamphetamine and two ring-isomers of both MDA and MDMA, we demonstrate the ability of IRIS to distinguish closely related NPS. Computationally predicted infrared (IR) spectra are shown to correspond with experimental spectra and could explain the molecular origins of their distinctive IR absorption bands. IRIS was then used to investigate a confiscated street sample containing two unknown substances. One substance could easily be identified by comparison to the IR spectra of reference standards. For the other substance, however, this approach proved inconclusive due to incomplete mass spectral databases as well as a lack of available reference compounds, two common analytical limitations resulting from the rapid development of NPS. Most excitingly, the second unknown substance could nevertheless be identified by using computationally predicted IR spectra of several potential candidate structures instead of their experimental reference spectra.

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.

Neutral loss of water and ammonia are often significant fragmentation channels upon collisional activation of protonated peptides. Here, we deploy infrared ion spectroscopy to investigate the dehydration reactions of protonated AlaSer, AlaThr, GlySer, GlyThr, PheSer, PheThr, ProSer, ProThr, AsnSer, and AsnThr, focusing on the question of the structure of the resulting [M + H - H2O](+) fragment ion and the site from which H2O is expelled. In all cases, the second residue of the selected peptides contains a hydroxyl moiety, so that H2O loss can potentially occur from this side-chain, as an alternative to loss from the C-terminal free acid of the dipeptide. Infrared action spectra of the product ions along with quantum-chemical calculations unambiguously show that dehydration consistently produces fragment ions containing an oxazoline moiety. This contrasts with the common oxazolone structure that would result from dehydration at the C-terminus analogous to the common b/y dissociation forming regular b(2)-type sequence ions. The oxazoline product structure suggests a reaction mechanism involving water loss from the Ser/Thr side-chain with concomitant nucleophilic attack of the amide carbonyl oxygen at its beta-carbon, forming an oxazoline ring. However, an extensive quantum-chemical investigation comparing the potential energy surfaces for three entirely different dehydration reaction pathways indicates that it is actually the backbone amide oxygen atom that leaves as the water molecule.

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.

In a previous study [Int. J. Mass Spectrom. 2010; 297: 67–75], the asymmetric O=U=O stretch (ν3) was measured for anionic uranyl complexes with composition [UO2(X)3]-, X = Cl-, Br- and I-. Within this group of complexes, the ν3 frequency red-shifts following the trend I > Br > Cl, suggesting concomitant weakening of the U=O bonds. However, a value for [UO2(F)3]- was not measured, which prevented a comprehensive comparison of measured ν3 positions to computed frequencies from density functional theory (DFT) calculations. Because the shift in ν3 is predicted to be most dramatic when X = F, we revisited these species using infrared multiple-photon photodissociation spectroscopy. As in our earlier study, a modest red-shift to the ν3 vibration of ∼ 6 cm-1 was observed for X = I-, Br-, and Cl-, and the position of the frequency follows the trend I- > Br- > Cl-. The value measured for [UO2(F)3]- is ∼43 cm-1 lower than the one measured for [UO2(Cl)3]-. Overall, the trend with respect to ν3 position is reproduced well by computed frequencies from DFT.

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.

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 ex- amples of strategies to address outstanding challenges.

We report the fingerprint IR spectra of mass-isolated gaseous coordination complexes of 2,2′-bipyridine (bpy) and 1,4,8,11-tetra-azacyclotetradecane (cyclam) with a copper ion in its I and II oxidation states. Experiments are carried out in a quadrupole ion trap (QIT) mass spectrometer coupled to the FELIX infrared free-electron laser. Dications are prepared using electrospray ionization (ESI), while monocations are generated by charge reduction of the dication using electron transfer-reduction (ETR) in the QIT. Interestingly, [Cu(bpy)2]+ can also be generated directly using ESI, so that its geometries as produced from ETR and ESI can be compared. The effects of charge reduction on the IR spectra are investigated by comparing the experimental spectra with the IR spectra modeled by density functional theory. Reduction of Cu(II) to the closed-shell Cu(I) ion retains the square-planar geometry of the Cu–cyclam complex. In contrast, for the bis–bpy complex with Cu, charge reduction induces a conversion from a near-square-planar to a tetrahedral geometry. The geometry of [Cu(bpy)2]+ is identical to that of the complex generated directly from ESI as a native structure, which indicates that the ETR product ion thermalizes. For [Cu(cyclam)]+, however, the square-planar geometry of the 2+ complex is retained upon charge reduction, although a (distorted) tetrahedral geometry was predicted to be lower in energy. These differences are attributed to different barriers to rearrangement.

The synthesis, reactivity, structures, and bonding in gas-phase binary and complex oxide anion molecules of protactinium and uranium have been studied by experiment and theory. The oxalate ions, AnVO2(C2O4)−, where An = Pa or U, are essentially actinyl ions, AnVO2+, coordinated by an oxalate dianion. Both react with water to yield the pentavalent hydroxides, AnVO(OH)2(C2O4)−. The chemistry of Pa and U becomes divergent for reactions that result in oxidation: whereas PaVI is inaccessible, UVI is very stable. The UVO2(C2O4)− complex exhibits a remarkable spontaneous exothermic replacement of the oxalate ligand by O2 to yield UO4– and two CO2 molecules. The structure of the uranium tetroxide anion is computed to correspond to distorted uranyl, UVIO22+, coordinated in the equatorial plane by two equivalent O atoms each having formal charges of −1.5 and U–O bond orders intermediate between single and double. The unreactive nature of PaVO2(C2O4)− toward O2 is a manifestation of the resistance toward oxidation of PaV, and clearly reveals the disparate chemistries of Pa and U. The uranium tetroxide anion, UO4–, reacts with water to yield UO5H2–. Infrared spectra obtained for UO5H2– confirm the computed lowest-energy structure, UO3(OH)2–.

The effect of ionization by oxidation and protonation on the structure and IR spectrum of isolated, gas-phase triphenylamine (TPA) has been investigated by infrared multiple photon dissociation (IRMPD) spectroscopy in the fingerprint range from 600 cm−1 to 1800 cm−1 using an infrared free electron laser. IR spectra calculated using density functional theory (DFT) convincingly reproduce the experimental data. Spectral and structural differences are identified among neutral TPA, TPA˙+ and protonated TPA and qualitatively related to effects of resonance delocalization. As a consequence of electron delocalization, computed structural parameters for TPA remain virtually unchanged upon removal of an electron. Nonetheless, CC and CN stretching vibrations in the IR spectra of TPA˙+ undergo a red shift of up to 52 cm−1 as compared to those in TPA. Since ionization also strongly influences the relative band intensities, a vibrational projection analysis was used to correlate vibrational modes of TPA with those of TPA˙+. The experimental IR spectrum of gas-phase protonated TPA indicates that protonation occurs on the nitrogen atom, despite delocalization of the lone electron pair. Upon protonation, the structure changes from the nearly planar geometry to a near-tetrahedral configuration.

High-performance liquid chromatography was used in combination with infrared ion spectroscopy for the identification of positional isomers of hydroxy-atorvastatins, the primary metabolites of the drug atorvastatin. The results demonstrate the direct applicability of infrared ion spectroscopy in the field of drug metabolism and, more generally, its promising role in state-of-the-art analytical laboratories for the identification of small molecules buried in complex mixtures. In combination with chromatographic separation, infrared spectroscopy of mass-selected ions provides a promising new route for the identification of the molecular structures of unknown m/z peaks in a mass spectrum. We demonstrate that currently existing experimental protocols allow the measurement of an IR spectrum from less than 10 ng of sample obtained in a collected HPLC fraction.

© The Royal Society of Chemistry 2016. Understanding of the nature and extent of chemical bonding in uranyl coordination complexes is crucial for the design of new ligands for nuclear waste separation, uranium extraction from seawater, and other applications. We report here the synthesis, infrared spectroscopic characterization, and quantum chemical studies of a molecular uranyl-di-15-crown-5 complex. The structure and bonding of this unique complex featuring a distinctive 6-fold coplanar coordination staggered sandwich structure and an unusual non-perpendicular orientation of the uranyl moiety are evaluated using density functional theory and chemical bonding analyses. The results provide fundamental understanding of the coordination interaction of uranyl with oxygen-donor ligands.

The observed variety of metal-ion complexation sites offered by peptides reflects a basic tension between charge solvation of the ion by Lewis-basic chelating groups versus amide nitrogen deprotonation and formation of metal–nitrogen bonds. Gas-phase models of metal-ion coordination can illuminate the factors governing this choice in condensed-phase proteins and enzymes. Here, structures of gas-phase complexes of Ni(II) and Cu(II) with tri- and tetra-peptide ligands are mapped out using a combination of Infrared Multiple Photon Dissociation (IRMPD) spectroscopy and density functional theory (DFT) computations. The two binding modes give distinctive IRMPD signatures, particularly in the diagnostic region 1500–1550 cm−1. Previous observations have suggested that Ni(II) complexes preferentially show the iminol rearrangement pattern (Im) giving low-spin square-planar geometries with metal-ion bonds to deprotonated amide nitrogens. In contrast, alkaline earth metal ion complexes prefer amide carbonyl oxygens chelating the metal ion with pyramidal geometry (charge-solvation, CS). Surprisingly, it is shown here that the Gly4 complexes are CS bound, in contrast with the expectation of Im binding. It is suggested that CS binding is actually a normal Ni(II) and Cu(II) binding mode to simple peptides lacking participating side chains. Three factors are suggested to influence the choice between CS and Im binding patterns: (1) presence of an accessible side-chain Lewis-basic proton interaction site (FGGF, FGG and HAA complexes); (2) short chain length of the peptide leading to a shortage of accessible carbonyl oxygen sites for CS binding, (AAA, FGG and HAA complexes); (3) outright deprotonation of the ligand giving net negatively charged Im[Ni2+(Gly4–3H+)]− and Im[Ni2+(Ala3–3H+)]− complexes, which have a triply-deprotonated ligand. IRMPD spectra of [Cu2+Gly4]2+ and [Cu2+(Gly4–3H+)]− complexes suggest that their structures are similar to their Ni2+ analogs.