Hydrogen Tag Shifts as Vibrational Reporters for Positional Isomers of Formylphenides: Surprising Mobility of the Carbanion Center upon Collisional Decarboxylation of the Parent Benzoates.

Infrared photodissociation of weakly bound "mass tags" is widely used to determine the structures of ions by analyzing their vibrational spectra. Molecular hydrogen is a common choice for tagging in cryogenic radio-frequency ion traps. Although the H2 molecules can introduce distortions in the target species, we demonstrate an advantage of H2 tagging in the analysis of positional isomers adopted by the molecular anions derived from decarboxylation of formylbenzoates. Attachment of H2 to the carbanion centers of three such isomers yields distinct shifts in the H2 stretch, which can be used to determine the distribution of isomers in an unknown sample. Electronic structure calculations indicate that the position-dependent shifts are due to different reactivities of the carbanion sites with respect to an intracluster proton-transfer reaction with the H2 molecule. We exploit this spectroscopic method to quantify the surprisingly facile migrations of the anionic center that have been previously reported for phenide rearrangements.

Characterization of the Oxazolone and Macrocyclic Motifs in the bn (n = 2-5) Product Ions from Collision-Induced Dissociation of Protonated Oligoglycine Peptides with Isomer-Selective, Cryogenic Vibrational Spectroscopy.

Collision-induced dissociation (CID) of small, protonated peptides leads to the formation of b-type fragment ions that can occur with several structural motifs driven by different covalent intramolecular bonding arrangements. Here, we characterize the so-called "oxazolone" and "macrocycle" bn ion structures that occur upon CID of oligoglycine peptides (Gn) ions (n = 2-6). This is determined by acquiring the vibrational band patterns of the cryogenically cooled, D2-tagged bn ions obtained using isomer-selective, two-color IR-IR photobleaching and analyzing them with predicted (DFT) harmonic spectra for the candidate structures. Both oxazolone and macrocyclic isomers are formed by b4, whereas only oxazolone species are created for b2 and b3 and the macrocycle is created for b5. As such, n = 4 corresponds to the minimum size where both Oxa and MC forms are present.

Structures and Chemical Rearrangements of Benzoate Derivatives Following Gas Phase Decarboxylation.

Decarboxylation of carboxylate ions in the gas phase provides a useful window into the chemistry displayed by these reactive carbanion intermediates. Here, we explore the species generated by decarboxylation of two benzoate derivatives: 2-formylbenzoate (2FBA) and 2-benzoylbenzoate (2BBA). The nascent product anions are transferred to a cryogenic ion trap where they are cooled to ∼15 K and analyzed by their pattern of vibrational bands obtained with IR photodissociation spectroscopy of weakly bound H2 molecules. The structures of the quenched species are then determined by comparison of these spectra with those predicted by electronic structure calculations for local minima on the potential energy surface. The 2-phenide carbanion generated by decarboxylation of 2FBA occurs in two isomeric forms that differ in the orientation of the formyl group, both of which yield a very large (∼110 cm-1) redshift in the stretching frequency of the H2 molecule attached to the anionic carbon center. Although calculated to be a local minimum, the analogous 2-phenide species could not be isolated upon decarboxylation of 2BBA. Rather, the anionic product adopts a ring-closed structure, indicating efficient nucleophilic attack on the pendant phenyl group by the nascent phenide. The barrier for ring closing is evaluated with electronic structure calculations.

Determination of the SmO+ bond energy by threshold photodissociation of the cryogenically cooled ion.

The SmO+ bond energy has been measured by monitoring the threshold for photodissociation of the cryogenically cooled ion. The action spectrum features a very sharp onset, indicating a bond energy of 5.596 ± 0.004 eV. This value, when combined with the literature value of the samarium ionization energy, indicates that the chemi-ionization reaction of atomic Sm with atomic oxygen is endothermic by 0.048 ± 0.004 eV, which has important implications on the reactivity of Sm atoms released into the upper atmosphere. The SmO+ ion was prepared by electrospray ionization followed by collisional breakup of two different precursors and characterized by the vibrational spectrum of the He-tagged ion. The UV photodissociation threshold is similar for the 10 K bare ion and the He tagged ion, which rules out the possible role of metastable electronically excited states. Reanalysis and remeasurement of previous reaction kinetics experiments that are dependent on D0(SmO+) are included, bringing all experimental results in accord.

On the Hydrogen Oxalate Binding Motifs onto Dinuclear Cu and Ag Metal Phosphine Complexes.

We report the binding geometries of the isomers that are formed when the hydrogen oxalate ((CO2 )2 H=HOx) anion attaches to dinuclear coinage metal phosphine complexes of the form [M1 M2 dcpm2 (HOx)]+ with M=Cu, Ag and dcpm=bis(dicyclohexylphosphino)methane, abbreviated [MM]+ . These structures are established by comparison of isomer-selective experimental vibrational band patterns displayed by the cryogenically cooled and N2 -tagged cations with DFT calculations of the predicted spectra for various local minima. Two isomeric classes are identified that feature either attachment of the carboxylate oxygen atoms to the two metal centers (end-on docking) or attachment of oxygen atoms on different carbon atoms asymmetrically to the metal ions (side-on docking). Within each class, there are additional isomeric variations according to the orientation of the OH group. This behavior indicates that HOx undergoes strong and directional coordination to [CuCu]+ but adopts a more flexible coordination to [AgAg]+ . Infrared spectra of the bare ions, fragmentation thresholds and ion mobility measurements are reported to explore the behaviors of the complexes at ambient temperature.

Chemical Reduction of NiII Cyclam and Characterization of Isolated NiI Cyclam with Cryogenic Vibrational Spectroscopy and Inert-Gas-Mediated High-Resolution Mass Spectrometry.

NiII cyclam (cyclam = 1,4,8,11-tetraazacyclotetradecane) is an efficient catalyst for the selective reduction of CO2 to CO. A crucial elementary step in the proposed catalytic cycle is the coordination of CO2 to a NiI cyclam intermediate. Isolation and spectroscopic characterization of this labile NiI species without solvent has proven to be challenging, however, and only partial IR spectra have previously been reported using multiple photon fragmentation of ions generated by gas-phase electron transfer to the NiII cyclam dication at 300 K. Here, we report a chemical reduction method that efficiently prepares NiI cyclam in solution. This enables the NiI complex to be transferred into a cryogenic photofragmentation mass spectrometer using inert-gas-mediated electrospray ionization. The vibrational spectra of the 30 K ion using both H2 and N2 messenger tagging over the range 800-4000 cm-1 were then measured. The resulting spectra were analyzed with the aid of electronic structure calculations, which show strong method dependence in predicted band positions and small molecule activation. The conformational changes of the cyclam ligand induced by binding of the open shell NiI cation were compared with those caused by the spherical, closed-shell LiI cation, which has a similar ionic radius. We also report the vibrational spectrum of a NiI cyclam complex with a strongly bound O2 ligand. The cyclam ligand supporting this species exhibits a large conformational change compared to the complexes with weakly bound N2 and H2, which is likely due to significant charge transfer from Ni to the coordinated O2.

Destruction and reconstruction of UO22+ using gas-phase reactions.

While the strong axial U[double bond, length as m-dash]O bonds confer high stability and inertness to UO22+, it has been shown that the axial oxo ligands can be eliminated or replaced in the gas-phase using collision-induced dissociation (CID) reactions. We report here tandem mass spectrometry experiments initiated with a gas-phase complex that includes UO22+ coordinated by a 2,6-difluorobenzoate ligand. After decarboxylation to form a difluorophenide coordinated uranyl ion, [UO2(C6F2H3)]+, CID causes elimination of CO, and then CO and C2H2 in sequential dissociation steps, to leave a reactive uranium fluoride ion, [UF2(C2H)]+. Reaction of [UF2(C2H)]+ with CH3OH creates [UF2(OCH3)]+, [UF(OCH3)2]+ and [UF(OCH3)2(CH3OH)]+. Cleavage of C-O bonds within these species results in the elimination of methyl cation (CH3+). Subsequent CID steps convert [UF(OCH3)2]+ to [UO2(F)]+ and similarly, [U(OCH3)3]+ to [UO2(OCH3)]+. Our experiments show removal of both uranyl oxo ligands in "top-down" CID reactions and replacement in "bottom-up" ion-molecule and dissociation steps.

Collision-induced dissociation of [UO2 (NO3 )(O2 )]- and reactions of product ions with H2 O and O2.

We recently reported a detailed investigation of the collision-induced dissociation (CID) of [UO2 (NO3 )3 ]- and [UO2 (NO3 )2 (O2 )]- in a linear ion trap mass spectrometer (J. Mass Spectrom. DOI:10.1002/jms.4705). Here, we describe the CID of [UO2 (NO3 )(O2 )]- which is created directly by ESI, or indirectly by simple elimination of O2 from [UO2 (NO3 )(O2 )2 ]- . CID of [UO2 (NO3 )(O2 )]- creates product ions as at m/z 332 and m/z 318. The former may be formed directly by elimination of O2 , while the latter required decomposition of a nitrate ligand and elimination of NO2 . DFT calculations identify a pathway by which both product ions can be generated, which involves initial isomerization of [UO2 (NO3 )(O2 )]- to create [UO2 (O)(NO2 )(O2 )]- , from which elimination of NO2 or O2 will leave [UO2 (O)(O2 )]- or [UO2 (O)(NO2 )]- , respectively. For the latter product ion, the composition assignment of [UO2 (O)(NO2 )]- rather than [UO2 (NO3 )]- is supported by ion-molecule reaction behavior, and in particular, the fact that spontaneous addition of O2 , which is predicted to be the dominant reaction pathway for [UO2 (NO3 )]- is not observed. Instead, the species reacts with H2 O, which is predicted to be the favored pathway for [UO2 (O)(NO2 )]- . This result in particular demonstrates the utility of ion-molecule reactions to assist the determination of ion composition. As in our earlier study, we find that ions such as [UO2 (O)(NO2 )]- and [UO2 (O)(O2 )]- form H2 O adducts, and calculations suggest these species spontaneously rearrange to create dihydroxides.

Collision-induced dissociation of [UO2 (NO3 )3 ]- and [UO2 (NO3 )2 (O2 )]- and reactions of product ions with H2 O and O2.

Electrospray ionization (ESI) can produce a wide range of gas-phase uranyl (UO2 2+ ) complexes for tandem mass spectrometry studies of intrinsic structure and reactivity. We describe here the formation and collision-induced dissociation (CID) of [UO2 (NO3 )3 ]- and [UO2 (NO3 )2 (O2 )]- . Multiple-stage CID experiments reveal that the complexes dissociate in reactions that involve elimination of O2 , NO2 , or NO3 , and subsequent reactions of interesting uranyl-oxo product ions with (neutral) H2 O and/or O2 were investigated. Density functional theory (DFT) calculations reproduce experimental results and show that dissociation of nitrate ligands, with ejection of neutral NO2 , is favored for both [UO2 (NO3 )3 ]- and [UO2 (NO3 )2 (O2 )]- . DFT calculations also suggest that H2 O adducts to products such as [UO2 (O)(NO3 )]- spontaneously rearrange to create dihydroxides and that addition of O2 is favored over addition of H2 O to formally U(V) species.

Characterization of the non-covalent docking motif in the isolated reactant complex of a double proton-coupled electron transfer reaction with cryogenic ion spectroscopy.

The solution kinetics of a proton-coupled electron transfer reaction involving two-electron oxidation of a Ru compound with concomitant transfer of two protons to a quinone derivative have been interpreted to indicate the formation of a long-lived intermediate between the reactants. We characterize the ionic reactants, products, and an entrance channel reaction complex in the gas phase using high-resolution mass spectrometry augmented by cryogenic ion IR photodissociation spectroscopy. Collisional activation of this trapped entrance channel complex does not drive the reaction to products but rather yields dissociation back to reactants. Electronic structure calculations indicate that there are four low-lying isomeric forms of the non-covalently bound complex. Comparison of their predicted vibrational spectra with the observed band pattern indicates that the C=O groups of the ortho-quinone attach to protons on two different -NH2 groups of the reactant scaffold, exhibiting strong O-H-N contact motifs. Since collisional activation does not lead to the products observed in the liquid phase, these results indicate that the reaction most likely proceeds through reorientation of the H-atom donor ligand about the metal center.

Characterization of the alkali metal oxalates (MC2O4-) and their formation by CO2 reduction via the alkali metal carbonites (MCO2-).

The reduction of carbon dioxide to oxalate has been studied by experimental Collisionally Induced Dissociation (CID) and vibrational characterization of the alkali metal oxalates, supplemented by theoretical electronic structure calculations. The critical step in the reductive process is the coordination of CO2 to an alkali metal anion, forming a metal carbonite MCO2- able to subsequently receive a second CO2 molecule. While the energetic demand for these reactions is generally low, we find that the degree of activation of CO2 in terms of charge transfer and transition state energies is the highest for lithium and systematically decreases down the group (M = Li-Cs). This is correlated to the strength of the binding interaction between the alkali metal and CO2, which can be related to the structure of the oxalate moiety within the product metal complexes evolving from a planar to a staggered conformer with increasing atomic number of the interacting metal. Similar structural changes are observed for crystalline alkali metal oxalates, although the C2O42- moiety is in general more planar in these, a fact that is attributed to the increased number of interacting alkali metal cations compared to the gas-phase ions.

Integration of High-Resolution Mass Spectrometry with Cryogenic Ion Vibrational Spectroscopy.

We describe an instrumental configuration for the structural characterization of fragment ions generated by collisional dissociation of peptide ions in the typical MS2 scheme widely used for peptide sequencing. Structures are determined by comparing the vibrational band patterns displayed by cryogenically cooled ions with calculated spectra for candidate structural isomers. These spectra were obtained in a linear action mode by photodissociation of weakly bound D2 molecules. This is accomplished by interfacing a Thermo Fisher Scientific Orbitrap Velos Pro to a cryogenic, triple focusing time-of-flight photofragmentation mass spectrometer (the Yale TOF spectrometer). The interface involves replacement of the Orbitrap's higher-energy collisional dissociation cell with a voltage-gated aperture that maintains the commercial instrument's standard capabilities while enabling bidirectional transfer of ions between the high-resolution FT analyzer and external ion sources. The performance of this hybrid instrument is demonstrated by its application to the a1, y1 and z1 fragment ions generated by CID of a prototypical dipeptide precursor, protonated L-phenylalanyl-L-tyrosine (H+-Phe-Tyr-OH or FY-H+). The structure of the unusual z1 ion, nominally formed after NH3 is ejected from the protonated tyrosine (y1) product, is identified as the cyclopropane-based product is tentatively identified as a cyclopropane-based product.

Isotope labeling and infrared multiple-photon photodissociation investigation of product ions generated by dissociation of [ZnNO3(CH3OH)2]+: Conversion of methanol to formaldehyde.

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.

Gas Phase Reactions of Ions Derived from Anionic Uranyl Formate and Uranyl Acetate Complexes.

The speciation and reactivity of uranium are topics of sustained interest because of their importance to the development of nuclear fuel processing methods, and a more complete understanding of the factors that govern the mobility and fate of the element in the environment. Tandem mass spectrometry can be used to examine the intrinsic reactivity (i.e., free from influence of solvent and other condensed phase effects) of a wide range of metal ion complexes in a species-specific fashion. Here, electrospray ionization, collision-induced dissociation, and gas-phase ion-molecule reactions were used to create and characterize ions derived from precursors composed of uranyl cation (UVIO22+) coordinated by formate or acetate ligands. Anionic complexes containing UVIO22+ and formate ligands fragment by decarboxylation and elimination of CH2=O, ultimately to produce an oxo-hydride species [UVIO2(O)(H)]-. Cationic species ultimately dissociate to make [UVIO2(OH)]+. Anionic complexes containing acetate ligands exhibit an initial loss of acetyloxyl radical, CH3CO2•, with associated reduction of uranyl to UVO2+. Subsequent CID steps cause elimination of CO2 and CH4, ultimately to produce [UVO2(O)]-. Loss of CH4 occurs by an intra-complex H+ transfer process that leaves UVO2+ coordinated by acetate and acetate enolate ligands. A subsequent dissociation step causes elimination of CH2=C=O to leave [UVO2(O)]-. Elimination of CH4 is also observed as a result of hydrolysis caused by ion-molecule reaction with H2O. The reactions of other anionic species with gas-phase H2O create hydroxyl products, presumably through the elimination of H2. Graphical Abstract ᅟ.

Common Questions About Streptococcal Pharyngitis.

Group A beta-hemolytic streptococcal (GABHS) infection causes 15% to 30% of sore throats in children and 5% to 15% in adults, and is more common in the late winter and early spring. The strongest independent predictors of GABHS pharyngitis are patient age of five to 15 years, absence of cough, tender anterior cervical adenopathy, tonsillar exudates, and fever. To diagnose GABHS pharyngitis, a rapid antigen detection test should be ordered in patients with a modified Centor or FeverPAIN score of 2 or 3. First-line treatment for GABHS pharyngitis includes a 10-day course of penicillin or amoxicillin. Patients allergic to penicillin can be treated with firstgeneration cephalosporins, clindamycin, or macrolide antibiotics. Nonsteroidal anti-inflammatory drugs are more effective than acetaminophen and placebo for treatment of fever and pain associated with GABHS pharyngitis; medicated throat lozenges used every two hours are also effective. Corticosteroids provide only a small reduction in the duration of symptoms and should not be used routinely.

Collision-induced dissociation of uranyl-methoxide and uranyl-ethoxide cations: Formation of UO2 H(+) and uranyl-alkyl product ions.

RATIONALE: The lower levels of adventitious H2 O in a linear ion trap allow the fragmentation reactions of [UO2 OCH3 ](+) and [UO2 OCH2 CH3 ](+) to be examined in detail. METHODS: Methanol- and ethanol-coordinated UO2 (2+) -alkoxide precursors were generated by electrospray ionization (ESI). Multiple-stage tandem mass spectrometry (MS(n) ) and collision-induced dissociation (CID) were performed using a linear ion trap mass spectrometer. RESULTS: CID of [UO2 OCH3 (CH3 OH)n ](+) and [UO2 OCH2 CH3 (CH3 CH2 OH)n ](+) , n = 3 and 2, causes loss of neutral alcohol ligands, leading ultimately to bare uranyl-alkoxide species. Comparison of 'native' to deuterium-labeled precursors reveals dissociation pathways not previously observed in 3-D ion trap experiments. CONCLUSIONS: UO2 H(+) is generated from [UO2 OCH3 ](+) by transfer of H from the methyl group. Variable-energy and variable-time CID experiments suggest that the apparent threshold for production of UO2 H(+) is lower than for UO2 (+) , but the pathway is kinetically less favored for the former than for the latter. CID experiments reveal that [UO2 OCH2 CH3 ](+) dissociates to generate [UO2 CH3 ](+) , a relatively rare species with a U-C bond, and [UO2 (O = CH2 )](+) .