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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., Evaluation of four table-top IR lasers for ion spectroscopy in ion trap mass spectrometers shows high rep-rate lasers offer better photodissociation efficiency and are more cost-effective and practical compared to low rep-rate or cw alternatives.

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.

Sodiated complexes of the aliphatic amino acids, Gly, Ala, Val, Leu, and Ile, were examined with infrared multiple-photon dissociation action spectroscopy utilizing light from a free-electron laser. To identify structures, the experimental spectra were compared to linear spectra calculated at the B3LYP/6-311+G(d,p) level of theory. Relative energetics of all complexes were calculated at B3LYP, B3P86, MP2(full), B3LYP-GD3BJ, and M06-2X levels using a 6-311+G(2d,2p) basis set. Spectral comparison for all complexes indicates that the dominant conformation, [N, CO], binds to the amino nitrogen and carbonyl oxygen. For all complexes except Gly, contributions are observed from [CO2-] structures, where the sodium cation binds to both oxygens of the carboxylate group in the zwitterionic form of the amino acid. The semiquantitative distribution between these two structures appears to be best-predicted by the B3LYP and MP2(full) levels of theory, with predictions from the other three levels inconsistent with the experiment.

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.

Contains fulltext : 237516.pdf (Publisher’s version ) (Open Access) BackgroundPyridoxine-dependent epilepsy (PDE-ALDH7A1) is an inborn error of lysine catabolism that presents with refractory epilepsy in newborns. Biallelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase/antiquitin, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important cofactor pyridoxal-5'-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but intellectual disability may still develop. Early diagnosis and treatment, preferably based on newborn screening, could optimize long-term clinical outcome. However, no suitable PDE-ALDH7A1 newborn screening biomarkers are currently available.MethodsWe combined the innovative analytical methods untargeted metabolomics and infrared ion spectroscopy to discover and identify biomarkers in plasma that would allow for PDE-ALDH7A1 diagnosis in newborn screening.ResultsWe identified 2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylic acid (2-OPP) as a PDE-ALDH7A1 biomarker, and confirmed 6-oxopiperidine-2-carboxylic acid (6-oxoPIP) as a biomarker. The suitability of 2-OPP as a potential PDE-ALDH7A1 newborn screening biomarker in dried bloodspots was shown. Additionally, we found that 2-OPP accumulates in brain tissue of patients and Aldh7a1-knockout mice, and induced epilepsy-like behavior in a zebrafish model system.ConclusionThis study has opened the way to newborn screening for PDE-ALDH7A1. We speculate that 2-OPP may contribute to ongoing neurotoxicity, also in treated PDE-ALDH7A1 patients. As 2-OPP formation appears to increase upon ketosis, we emphasize the importance of avoiding catabolism in PDE-ALDH7A1 patients.FundingSociety for Inborn Errors of Metabolism for Netherlands and Belgium (ESN), United for Metabolic Diseases (UMD), Stofwisselkracht, Radboud University, Canadian Institutes of Health Research, Dutch Research Council (NWO), and the European Research Council (ERC).

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.

Metallated gas-phase structures consisting of an intact and deprotonated histidine (His) ligand, M(His-H)(His)+, where M = Ca and Ni, were examined using infrared multiple photon dissociation (IRMPD) action spectroscopy utilizing light from a free-electron laser (FEL). In parallel, ab initio quantum-chemical calculations identified several low-energy isomers for each complex. Experimental action spectra were compared to linear absorption spectra calculated at the B3LYP level of theory, using the 6-311+G(d,p) basis set. Single-point energies were calculated at B3LYP, B3LYP-GD3BJ, B3P86, and MP2(full) levels using the 6-311+G(2d,2p) basis set. For Ca(His-H)(His)+, the dominant structure has the metal center coordinating with the π nitrogen of the imidazole ring (Nπ) and both oxygen atoms of the carboxylate group of the deprotonated His ligand while coordinating with the backbone amine (Nα), Nπ, and the carbonyl oxygen of the carboxylic acid of the intact His ligand. The Ni(His-H)(His)+ species coordinates the metal ion through Nα, Nπ, and the carbonyl oxygen for both the deprotonated and intact His ligands, but also shows evidence for a minor secondary structure where the deprotonated His coordinates the metal at Nα, Nπ, and the deprotonated carbonyl oxygen and the intact His ligand is zwitterionic, coordinating the metal with both carboxylate oxygens. Different levels of theory predict different ground structures, highlighting the need for utilizing multiple levels of theory to help identify the gas-phase structure actually observed experimentally.

A key decay pathway by which organic sunscreen molecules dissipate harmful UV energy involves excited-state hydrogen atom transfer between proximal enol and keto functional groups. Structural modifications of this molecular architecture have the potential to block ultrafast decay processes, and hence promote direct excited-state molecular dissociation, profoundly affecting the efficiency of an organic sunscreen. Herein, we investigate the binding of alkali metal cations to a prototype organic sunscreen molecule, oxybenzone, using IR characterization. Mass-selective IR action spectroscopy was conducted at the free electron laser for infrared experiments, FELIX (600-1800 cm-1), on complexes of Na+, K+ and Rb+ bound to oxybenzone. The IR spectra reveal that K+ and Rb+ adopt binding positions away from the key OH intermolecular hydrogen bond, while the smaller Na+ cation binds directly between the keto and enol oxygens, thus breaking the intramolecular hydrogen bond. UV laser photodissociation spectroscopy was also performed on the series of complexes, with the Na+ complex displaying a distinctive electronic spectrum compared to those of K+ and Rb+, in line with the IR spectroscopy results. TD-DFT calculations reveal that the origin of the changes in the electronic spectra can be linked to rupture of the intramolecular bond in the sodium cationized complex. The implications of our results for the performance of sunscreens in mixtures and environments with high concentrations of metal cations are discussed.

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 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.

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.

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.

Characterizing the chemical composition of organic aerosols can elucidate aging mechanisms as well as the chemical and physical properties of the aerosol. However, the high chemical complexity and often low atmospheric abundance present a difficult analytical challenge. Milligrams or more of material may be needed for speciated spectroscopic analysis. In contrast, mass spectrometry provides a very sensitive platform but limited structural information. Here, we combine the strengths of mass spectrometry and infrared (IR) action spectroscopy to generate characteristic IR spectra of individual, mass-isolated ion populations. Soft ionization combined with in situ infrared ion spectroscopy, using the tunable free-electron laser FELIX, provides detailed information on molecular structures and functional groups. We apply this technique, along with quantum mechanical modeling, to characterize organic molecules in secondary organic aerosol (SOA) formed from the ozonolysis of alpha-pinene. Spectral overlap with a standard is used to identify cis-pinonic acid. We also demonstrate the characterization of isomers for multiple SOA products using both quantum mechanical computations and analyses of fragment ion spectra. These results demonstrate the detailed structural information on isolated ions obtained by combining mass spectrometry with fingerprint IR spectroscopy.

The input power of a CO 2 microwave plasma is modulated at kHz rate in scans of duty cycle at constant average power to investigate gas heating dynamics and its relation to dissociation efficiency. Rotational temperature profiles obtained from rotational Raman scattering reveal peak temperatures of up to 3000 , while the edge temperature remains cold (500 ). During the plasma 'OFF'-period, the gas cools down convectively, but remains overall too hot to allow for strong overpopulation of vibrational modes (2200 in the core). Fast optical imaging monitors plasma volume variations and shows that power density scales with peak power. As dissociation scales with observed peak rotational temperature, it is concluded that thermal processes dominate. A simple 0D model is constructed which explains how higher power density favors dissociation over radial energy transport. Thermal decomposition is reviewed in relation to quenching oxygen radicals with vibrationally excited CO 2, to reflect on earlier reported record efficiencies of 90%.

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.

Gas-phase coronene cations (C24H12+) can be sequentially hydrogenated with up to 24 additional H atoms, inducing a gradual transition from a planar, aromatic molecule towards a corrugated, aliphatic species. The mass spectra of hydrogenated coronene cations [C24H12+nH ]+ show that molecules with odd numbers of additional hydrogen atoms (nH) are dominant with particularly high relative intensity for ”magic numbers” nH = 5, 11, and 17, for which hydrogen atoms have the highest binding energies. Reaction barriers and binding energies strongly affect the hydrogenation sequence and its site specificity. In this contribution, we monitor this sequence experimentally by the evolution of infrared multiple-photon dissociation (IRMPD) spectra of gaseous [C24H12+nH]+ with nH = 3 − 11, obtained using an infrared free electron laser coupled to a Fourier transform ion cyclotron mass spectrometer.For weakly hydrogenated systems (nH = 3, 5) multiple-photon absorption mainly leads to loss of Hatoms (and/or H2). With increasing nH, C2H2 loss becomes more relevant. For nH = 9, 11, the carbon skeleton is substantially weakened and fragmentation is distributed over a large number of channels. A comparison of our IRMPD spectra with density functional theory calculations clearly shows that only one or two hydrogenation isomers contribute for each nH. This confirms the concept of hydrogenationoccurring along very specific sequences. Moreover, the atomic sites participating in the first 11 steps of this hydrogenation sequence are clearly identified.

© 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.

Gas phase infrared dissociation spectra of the radical cation, deprotonated and protonated forms of the hormone melatonin, and its complexes with alkali (Li+, Na+, and K+) and alkaline earth metal ions (Mg2+, Ca2+, and Sr2+) are measured in the spectral range 800–1800 cm−1. Minimum energy geometries calculated at the B3LYP/LACVP++** level are used to assign structural motifs to absorption bands in the experimental spectra. The melatonin anion is deprotonated at the indole-N. The indole-C linking the amide chain is the most favored protonation site. Comparisons between the experimental and calculated spectra for alkali and alkaline earth metal ion complexes reveal that the metal ions interact similarly with the amide and methoxy oxygen atoms. The amide I band undergoes a red shift with increasing charge density of the metal ion and the amide II band shows a concomitant blue shift. Another binding motif in which the metal ions interact with the amide-O and the π-electron cloud of the aromatic group is identified but is higher in energy by at least 18 kJ/mol. Melatonin is deprotonated at the amide-N with Mg2+ and the metal ion coordinates to the amide-N and an indole-C or the methoxy-O. These results provide information about the intrinsic binding of metal ions to melatonin and combined with future studies on solvated melatonin-metal ion complexes may help elucidate the solvent effects on metal ion binding in solution and the biochemistry of melatonin. These results also serve as benchmarks for future theoretical studies on melatonin-metal ion interactions.

Arginine (Arg) complexes with Zn2+ and Cd2+ were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light from a free electron laser. Electrospray ionization generated complexes of deprotonated Arg with Zn2+, [Zn(Arg–H)]+, and Arg with CdCl+, CdCl+(Arg). Possible low-energy conformers of these species were found using quantum chemical calculations, and their calculated IR spectra were compared to experimentally measured IRMPD spectra. Calculations were performed at the B3LYP/6-311+G(d,p) level for Zn2+ complexes and B3LYP/def2-TZVP with an SDD effective core potential on cadmium for CdCl+ complexes. [Zn(Arg–H)]+ was found to adopt a charge-solvated, tridentate [N,CO−,Nω′] structure where Zn2+ binds to the backbone amine, carbonyl oxygen, and side-chain terminal guanidine nitrogen (Nω′). The CdCl+(Arg) species was suggested to be a mixture of a dominant (∼85%) charge-solvated, tridentate [N,CO,Nω′] structure where the CdCl+ binds to the backbone amine, carbonyl, and side-chain imine (Nω′) and a minor (∼15%) bidentate [N,CO−](Nω′H2+) zwitterionic structure where the metal center binds to the backbone amine and carbonyl oxygen with intramolecular proton migration from the hydroxyl to the Nω′ guanidine nitrogen (as designated in parenthesis).

The gas-phase structures of protonated thymidine, [dThd + H](+), and its modified form, protonated 5-methyluridine, [Thd + H](+), are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy combined with electronic structure calculations. IRMPD action spectra are measured over the ranges extending from similar to 600 to 1900 cm(-1) and similar to 2800 to 3800 cm(-1) using the FELIX free electron laser and an optical parametric oscillator/amplifier (OPO/OPA) laser system, respectively. Comparisons between the B3LYP/6-311+G(d,p) linear IR spectra calculated for the stable low-energy conformers and the measured IRMPD spectra are used to determine the most favorable tautomeric conformations of [dThd + H](+) and [Thd + H](+) and to identify those populated in the experiments. Both B3LYP and MP2 levels of theory predict a minor 2,4-dihydroxy tautomer as the ground-state conformer of [dThd + H](+) and [Thd + H](+) indicating that the 2'-hydroxyl substituent of Thd does not exert a significant impact on the structural features. [dThd + H](+) and [Thd + H](+) share parallel IRMPD spectral profiles and yields in both the FELIX and OPO regions. Comparisons between the measured IRMPD and calculated IR spectra suggest that minor 2,4-dihydroxy tautomers and O2 protonated conformers of [dThd + H](+) and [Thd + H](+) are populated in the experiments. Comparison of this work to our previous IRMPD spectroscopy study of protonated 2'-deoxyuridine and uridine suggests that the 5-methyl substituent alters the preferences of O2 versus O4 protonation.

The capability of infrared multiple photon dissociation (IRMPD) spectroscopy to gain structural information on surfactant-based supramolecular aggregates has been exploited to elucidate intermolecular interactions and local organization of positively charged sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) aggregates in the gas phase. A detailed analysis of the stretching modes of the AOTNa CO and SO(3)(-) head groups allows one to directly probe their interactions with sodium counterions and to gain insight in their organization within the aggregate. Similarities and differences of the IRMPD spectra as compared to the infrared absorption spectrum of micellized AOTNa in CCl(4) have been analyzed. They strongly suggest a reverse micelle-like organization of AOTNa charged aggregates in the gas phase. Apart from low-abundance fragmentation channels of the AOTNa (molecule) itself, the main dissociation pathway of singly charged surfactant aggregates is the loss of neutral surfactant molecules, while doubly charged aggregates dissociate preferentially by charge separation forming singly charged species. In both cases, decomposition leads to the formation of the most energetically stable charged fragments.

The structures of Gly3·X−, Ala3·X− and Leu3·X− (X = Cl, Br and I) are investigated with computational chemistry and infrared multiple-photon dissociation (IRMPD) spectroscopy. Low-energy structures calculated at the B3LYP/6-31+G** level of theory (or with the CRENBL basis set and effective core potential implemented for Br and I) for these complexes have similar structural motifs in which the halide anion binds to the peptide via hydrogen bonds at amide, amine, and/or carboxylic acid H atoms. The IRMPD spectra do not depend significantly on anion identity. Comparisons between measured spectra and those calculated for low-energy structures of each of the chloridated complexes indicate that all three complexes have similar binding motifs. These results suggest that the size of the alkyl side chain does not significantly influence how halide anions bind to these peptides. The coordination geometries of Gly3·X− and Ala3·X− are “inverted” compared to those for the Na+ cationized peptides, where the peptides coordinate to Na+ via lone pair electrons of O and N atoms. The “inversion” in structures between Ala3·Na+ and Ala3·X− results in greater steric hindrance for some geometries of the latter. There is a subtle blue shift in the C-terminal C O stretch frequency with increasing halide anion size for each peptide, consistent with contributions from Stark and charge transfer effects. In contrast, the N H bends red shift with increasing halide anion size, which can only be attributed to the charge transfer effect. This is the first report of IR spectra of peptides complexed with anions, and these results provide insights into anion-peptide binding interactions.

The fragmentation chemistry of protonated sulfoserine was probed using a combination of collision-induced dissociation (CID) mass spectrometry, infrared multiple photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. The IRMPD spectra of the dominant fragment ions at m/z 106 and 88 (i.e., loss of SO3 and H2SO4) were obtained and used to determine the corresponding structures. By comparison to a synthetic standard and calculations, it was determined that the m/z 106 ion is structurally identical to protonated serine. The m/z 88 fragment ion was assigned an aziridine structure based on a comparison to theory, analogous to the structure previously proposed by others for phosphoric acid loss from phosphoserine. This work provides the first spectroscopic insights into the dissociation pathways of a sulfated amino acid, laying the groundwork for future studies on related amino acids and peptides with this important, labile post-translational modification.

The gas-phase conformations of protonated uridine, [Urd+H](+), and its modified form, protonated 2'-deoxyuridine, [dUrd+H](+), generated by electrospray ionization are investigated using infrared multiple photon dissociation (IRMPD) action spectroscopy techniques. IRMPD action spectra of [Urd+H](+) and [dUrd+H](+) are measured over the IR fingerprint and hydrogen-stretching regions. [Urd+H](+) and [dUrd+H](+) exhibit very similar IRMPD spectral profiles. However, the IRMPD yields of [Urd+H](+) exceed those of [dUrd+H](+) in both the IR fingerprint and hydrogen-stretching regions. The measured spectra are compared to the linear IR spectra predicted for the stable low-energy structures of these species computed at the B3LYP/6-311+G(d,p) level of theory to determine the tautomeric conformations populated by electrospray ionization. Both B3LYP and MP2 methods find O4 and O2 protonated canonical as well as 2,4-dihydroxy tautomers among the stable low-energy structures of [Urd+H](+) and [dUrd+H](+). Comparison between the measured IRMPD and calculated linear IR spectra suggests that these species exist in their ring-closed forms and that both 2,4-dihydroxy tautomers as well as O4 protonated canonical conformers coexist in the population generated by electrospray ionization for both [Urd+H](+) and [dUrd+H](+). The 2'-deoxy modification of [dUrd+H](+) reduces the variety of 2,4-dihydroxy tautomers populated in the experiments vs. those of [Urd+H](+).

Infrared spectra of the isolated protonated flavin molecules lumichrome, lumiflavin, riboflavin (vitamin B-2), and the biologically important cofactor flavin mononucleotide are measured in the fingerprint region (600-1850 cm(-1)) by means of IR multiple-photon dissociation (IRMPD) spectroscopy. Using density functional theory calculations, the geometries, relative energies, and linear IR absorption spectra of several low-energy isomers are calculated. Comparison of the calculated IR spectra with the measured IRMPD spectra reveals that the N10 substituent on the isoalloxazine ring influences the protonation site of the flavin. Lumichrome, with a hydrogen substituent, is only stable as the N1-protonated tautomer and protonates at N5 of the pyrazine ring. The presence of the ribityl unit in riboflavin leads to protonation at N1 of the pyrimidinedione moiety, and methyl substitution in lumiflavin stabilizes the tautomer that is protonated at O2. In contrast, flavin mononucleotide exists as both the O2- and N1-protonated tautomers. The frequencies and relative intensities of the two C=O stretch vibrations in protonated flavins serve as reliable indicators for their protonation site.

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

A gas-phase radical rearrangement through intramolecular hydrogen-atom transfer (HAT) was studied in the glutathione radical cation, [-ECG](+.), which was generated by a homolytic cleavage of the protonated S-nitrosoglutathione. Ion-molecule reactions suggested that the radical migrates from the original sulfur position to one of the -carbon atoms. Experiments on the radical cations of dipeptides derived from the glutathione sequence, [-EC](+.) and [CG](+.), pointed to the glutamic acid -carbon atom as the most likely site of the radical migration. Infrared multiple-photon dissociation (IRMPD) spectroscopy was employed to generate complementary information. IRMPD of [-ECG](+.) in the approximately 1000-1800cm(-1) region was inconclusive owing to the relatively broad, overlapping absorption bands. However, the IRMPD spectrum of [-EC](+.) in this region was consistent with the radical migrating from the sulfur to the -carbon atom of glutamic acid. IRMPD in the 2800-3700cm(-1) region performed on [-ECG](+.) is consistent with a mixture of both the original sulfur-based radical and the resulting glutamic acid -carbon-based species. Comparisons are made with previously published condensed and gas-phase studies on intramolecular HAT in glutathione.

Binding to proteins and peptides in condensed phases, it is normal for alkali and alkaline earth metal ions to interact preferentially with Lewis-basic oxygen, nitrogen and similar open chelation points, while late transition metals like cobalt, nickel and copper characteristically deprotonate and bind to amide nitrogens along the peptide chain. Parallel to these contrasting condensed-phase binding-mode alternatives, metal ions in the gas phase can form complexes with small peptides in several complexation modes, among them the charge-solvated (CS) and the Iminol patterns. Reported here is a computational study of the factors determining the choice between these patterns in the gas phase for model ligands, dialanine and trialanine, also including illustrative experimental spectroscopic results for Ag + (Ala) 3 using the infrared multiple photon dissociation (IRMPD) technique (which has also provided previous experimental results for many of the ions studied here). Across a survey of 29 metal ions in normal oxidation states (+1, +2 and +3), unexpectedly strong correlations are found (for each charge state) between the preference for CS versus Iminol binding and the overall binding energies of the ions. Ions of +1 charge invariably prefer CS binding, while those with higher charge exhibit variable preferences. Within a given charge state, Iminol binding is more favorable, and overall binding is stronger, for light metal ions and for metal ions (“transition metals”) late in the periodic table. The tendency to go from CS to Iminol in the gas phase is generally parallel to the tendency to bind deprotonated amide nitrogens in condensed-phase, but with possible divergence between the differing environments at the point where the tendencies cross over near Mg(II). Hard/soft character of the metal ions correlates to some extent with the binding preferences, but this correlation shows numerous discrepancies. For “main-group” metal ions, electrostatic character of the binding is suggested by excellent scaling of binding energies with a scaling parameter q / R , while a contribution of enhanced binding in addition to the electrostatic binding energy is indicated for “transition” metals.

The gas-phase structures of alkali metal cationized complexes of cyclen (1,4,7,10-tetraazacyclododecane) are examined via infrared multiple photon dissociation (IRMPD) action spectroscopy and electronic structure theory calculations. The measured IRMPD action spectra of four M+(cyclen) complexes are compared to IR spectra predicted for the stable low-lying conformers of these complexes calculated at the B3LYP/def2-TZVPPD level of theory to identify the structures accessed in the experiments. The IRMPD yields of the M+(cyclen) complexes investigated increase as the size of the alkali metal cation increases, in accordance with the decrease in the strength of alkali metal cation binding. The IRMPD spectrum of the Na+(cyclen) complex is relatively simple, and the features observed are retained for all of the other alkali metal cation–cyclen complexes. New spectral features begin to appear for K+(cyclen) and become very obvious for the Rb+(cyclen) and Cs+(cyclen) complexes. The IRMPD action spectra for the complexes of cyclen to K+, Rb+, and Cs+ are well reproduced by the calculated spectra predicted for the most stable conformations computed. Overall comparisons suggest that only the ground-state conformations of the M+(cyclen) complexes were accessed in the experiments for the complexes to Na+ and K+, whereas evidence for a very small population of the first excited conformers is observed for the complexes to Rb+ and Cs+.

The reactivity of the cysteine (Cys) and homocysteine (Hcy) radical cation was studied using ion molecule reactions. The radical cations were generated via collision-induced dissociation (CID) of their S-nitrosylated precursors. Cleavage of the S-NO bond led to the formation of the radical initially positioned on the sulfur atom. The reactions of the radical cations with dimethyl disulfide revealed that the cysteine radical cation reacts more quickly than the homocysteine radical cation. Infrared multiple photon dissociation (IRMPD) spectroscopy and density functional theory (DFT) calculations were used to determine the structure of the homocysteine radical cation, which was compared to the previously published structure of the cysteine radical cation (Sinha et al. Phys. Chem. Chem. Phys. 2010, 12, 9794-9800). IRMPD spectroscopy and DFT calculations revealed that this difference in radical reactivity was not a result of a radical rearrangement for the homocysteine radical cation but rather that the reactivity was modulated by stronger hydrogen bonding.

Collision-induced dissociation (CID) of the peptide alanine-4-aminomethylbenzoic acid-glycine, A(AMBz)G generates a prominent b(2) ion despite a previous report [ER. Talaty, T.J. Cooper, S.M. Osburn, M.J. Van Stipdonk, Collision-induced dissociation of protonated tetrapeptides containing beta-alanine, gamma-aminobutyric acid, e-aminocaproic acid or 4-aminomethylbenzoic acid residues, Rapid Commun. Mass Spectrom. 20 (2006) 3443-3455] which showed that incorporation of the aromatic amino acid into a peptide sequence inhibits generation of b(n) ions formed by cleavage to the immediate C-terminal side of the residue. Infrared multiple photon dissociation (IRMPD) spectroscopy and density functional theory (DFT) calculations suggest that the b(2) ion generated from A(AMBz)G has an acylium structure. The b2 ion generated from (AMBz)AG, in which the aromatic residue is situated at the amino-terminus, is instead a conventional oxazolone. (c) 2012 Elsevier B.V. All rights reserved.

A series of aluminium complex ions with trifluoromethyl-heteroarylalkenolato (TMHA) ligands are studied by gas-phase infrared multiphoton-dissociation (IRMPD) spectroscopy and computational modelling. The selected series of aluminium TMHA complex ions are promising species for the initial study of intrinsic binding characteristics of Al(III) cations in the gas phase as corresponding molecular ions. They are readily available for examination by (+) and (-) electrospray ionization mass spectrometry (ESI-MS) by spraying of [Al(3+)⋅(L(-))(3)] solutions. The complex ions under investigation contain trivalent Al(3+) cations with two chelating anionic enolate ligands, [Al(3+)⋅(L(-))(2)](+), providing insights in the nature of the heteroatom-Al bonds. Additionally, the structure of a deprotonated benzimidazole ligand, L(-,) and an anionic complex ion of Al(III) with two doubly deprotonated benzimidazole ligands, [Al(3+)⋅(L(2-))(2)](-), are examined by (-)ESI-IRMPD spectroscopy. Experimental and computational results are highly consistent and allow a reliable identification of the ion structures. In all complex ions examined the planar TMHA ligands are oriented perpendicular to each other around the metal ion, leading to a tetrahedral coordination sphere in which aluminium interacts with the enolate oxygen and heteroaryl nitrogen atoms available in each of the bidentate ligands.

Laser infrared multiple photon dissociation (IRMPD) spectroscopy has been employed to probe the C-O and C-C stretching vibrational modes of 18-crown-6 ether (18c6) complexes with alkaline-earth metals (Mg(2+), Ca(2+). Sr(2+) and Ba(2+)) stored in the cell of a Fourier Transform Ion Cyclotron Resonance mass spectrometer. Computations at the B3LYP/6-311++G(2d,2p) and B3LYP/aug-cc-pVDZ levels of theory agree well with the most salient features of the experimental spectra and allow to characterize the lower energy conformers for each type of complex. A pronounced shift of the C-O stretching band, but not of the C-C band, is found in comparison to the similar IRMPD spectra reported previously for the 18c6 complexes with alkali metals. This is attributed to the tighter coordination and stronger binding of the divalent alkaline-earth cations to the oxygen sites, and to the degree of folding of the crown ether backbone. Nevertheless, the conformational landscape and symmetry constraints of the complexes follow a pattern similar to that found for the alkali metal cations. The most stable conformers evolve from compact D(2) geometries for the smaller cations, Mg(2+) and Ca(2+), to more open C(2) configurations for Sr(2+) and to a planar D(3d) structure for Ba(2+). (C) 2011 Elsevier B.V. All rights reserved.

All eight D-aldohexoses and aldohexoses derived from the non-reducing end of disaccharides were investigated by variable-wavelength infrared multiple-photon dissociation (IRMPD) as anions in the negative-ion mode. Spectroscopic evidence supports the existence of a relatively abundant open-chain configuration of the anions in the gas phase, based on the observation of a significant carbonyl absorption band near 1710 cm(-1). The abundance of the open-chain configuration of the aldohexose anions was approximately 1000-fold or greater than that of the neutral sugars in aqueous solution. This provides an explanation as to why it has not been possible to discriminate the anomeric configuration of aldohexose anions in the gas phase when derived from the non-reducing sugar of a disaccharide. Evidence from photodissociation spectra also indicates that the different aldohexoses yield product ions with maximal abundances at different wavelengths, and that the carbonyl stretch region is useful for differentiation of sugar stereochemistries. Quantum-chemical calculations indicate relatively low energy barriers to intramolecular proton transfer between hydroxyl groups and adjacent alkoxy sites located on open-chain sugar anions, suggesting that an ensemble of alkoxy charge locations contributes to their observed photodissociation spectra. Ring opening of monosaccharide anions and interconversion among configurations is an inherent property of the ions themselves and occurs in vacuo independent of solvent participation. (C) 2011 Elsevier Ltd. All rights reserved.