Competitive proton and hydride transfer reactions via ion‐neutral complexes: fragmentation of deprotonated benzyl N‐phenylcarbamates in mass spectrometry

The gas‐phase chemistry of deprotonated benzyl N‐phenylcarbamates was investigated by electrospray ionization tandem mass spectrometry. Characteristic losses of a substituted phenylcarbinol and a benzaldehyde from the precursor ion were proposed to be derived from an ion‐neutral complex (INC)‐mediated competitive proton and hydride transfer reactions. The intermediacy of the INC consisting of a substituted benzyloxy anion and a phenyl isocyanate was supported by both ortho‐site‐blocking experiments and density functional theory calculations. Within the INC, the benzyloxy anion played the role of either a proton abstractor or a hydride donor toward its neutral counterpart. Relative abundances of the product ions were influenced by the nature of the substituents. Electron‐withdrawing groups at the N‐phenyl ring favored the hydrogen transfer process (including proton and hydride transfer), whereas electron‐donating groups favored direct decomposition to generate the benzyloxy anion (or substituted benzyloxy anion). By contrast, electron‐withdrawing and electron‐donating substitutions at the O‐benzyl ring exhibited opposite effects. Copyright © 2015 John Wiley & Sons, Ltd.     

Heterocyclic ring cleavage upon collision‐induced dissociation of deprotonated 3‐hydroxy‐1,2,5‐oxadiazoles (3‐hydroxyfurazans)

A series of 4‐substituted 3‐hydroxyfurazans were subjected to electrospray ionization tandem mass spectrometry. At low collision energy, oxyisocyanate ([O=C=N–O]^?, m/z 58) was formed as the predominant product ion from each deprotonated 3‐hydroxyfurazan, indicating cleavage of the heterocyclic ring. The facile energetics of this characteristic fragmentation process was confirmed by density functional computations.     

Study of gas‐phase reactions of NO2+ with aromatic compounds using proton transfer reaction time‐of‐flight mass spectrometry

The study of ion chemistry involving the NO₂⁺ is currently the focus of considerable fundamental interest and is relevant in diverse fields ranging from mechanistic organic chemistry to atmospheric chemistry. A very intense source of NO₂⁺ was generated by injecting the products from the dielectric barrier discharge of a nitrogen and oxygen mixture upstream into the drift tube of a proton transfer reaction time‐of‐flight mass spectrometry (PTR‐TOF‐MS) apparatus with H₃O⁺ as the reagent ion. The NO₂⁺ intensity is controllable and related to the dielectric barrier discharge operation conditions and ratio of oxygen to nitrogen. The purity of NO₂⁺ can reach more than 99% after optimization. Using NO₂⁺ as the chemical reagent ion, the gas‐phase reactions of NO₂⁺ with 11 aromatic compounds were studied by PTR‐TOF‐MS. The reaction rate coefficients for these reactions were measured, and the product ions and their formation mechanisms were analyzed. All the samples reacted with NO₂⁺ rapidly with reaction rate coefficients being close to the corresponding capture ones. In addition to electron transfer producing [M]⁺, oxygen ion transfer forming [MO]⁺, and 3‐body association forming [M·NO₂]⁺, a new product ion [M−C]⁺ was also formed owing to the loss of C═O from [MO]⁺.This work not only developed a new chemical reagent ion NO₂⁺ based on PTR‐MS but also provided significant interesting fundamental data on reactions involving aromatic compounds, which will probably broaden the applications of PTR‐MS to measure these compounds in the atmosphere in real time.     

Transformation of the gas‐phase favored O‐protomer of p‐aminobenzoic acid to its unfavored N‐protomer by ion activation in the presence of water vapor: An ion‐mobility mass spectrometry study

An ion‐mobility mass spectrometry study showed that the preferred O‐protonated form of p‐aminobenzoic in the gas phase can be converted to the thermodynamically less favored N‐protomer by in‐source collision‐induced ion activation during the ion transfer process from the atmospheric region to the first vacuum region if the humidity is high in the ion source. Upon the addition of water vapor to the nitrogen gas used to promote the solid analyte to the gas phase under helium‐plasma ionization conditions, the intensity of the ion‐mobility arrival‐time peak for the N‐protomer increased dramatically. Evidently, the ion‐activation process in the first vacuum region is able to provide the energy required to surmount the barrier to isomerize the O‐protomer to the more energetic N‐protomer. The transfer of the proton attached to the carbonyl oxygen atom of the O‐protomer to the amino group takes place by a water‐bridge mechanism. Apparently, the postionization transformations that take place during the transmission of ions from the atmospheric‐pressure ion source to the detector, via different physical compartments of low to high vacuum, play an eminent role in determining the population ratios eventually manifested at the detector.     

Imidazole and imidazolium porphyrins: gas‐phase chemistry of multicharged ions

Electrospray ionization mass spectrometry/mass spectrometry in the positive ion mode was used to investigate the gas‐phase chemistry of multicharged ions from solutions of porphyrins with 1,3‐dimethylimidazolium‐2‐yl (DMIM) and 1‐methylimidazol‐2‐yl (MIm) meso‐substituents. The studied compounds include two free bases and 12 complexes with transition metals (Cu(II), Zn(II), Mn(III), and Fe(III)). The observed multicharged ions are either preformed or formed during the electrospraying process by reduction or protonation and comprise closed‐shell and hypervalent mono‐radical and bi‐radical ions. The observed extensive and abundant fragmentation of the DMIM and MIm meso‐substituents is a characteristic feature of these porphyrins. Fragments with the same mass values can be lost from the meso‐substituents either as charged or neutral species and from closed‐shell and hypervalent radical ions. Reduction processes are observed for both the free bases and the metallated DMIM porphyrins and occur predominantly by formation of hypervalent radicals that fragment, at low energy collisions, by loss of methyl radicals with formation of the corresponding MIm functionalities. These findings confirm that, when using electrospray ionization, reduction is an important characteristic of cationic meso‐substituted tetrapyrrolic macrocycles, always occurring when delocalization of the formed hypervalent radicals is possible. For the Fe(III) and Mn(III) complexes, reduction of the metal centers is also observed as the predominant fragmentation of the corresponding reduced ions through losses of charged fragments testifies. The fragmentation of the closed‐shell ions formed by protonation of the MIm porphyrins mirrors the fragmentation of the closed‐shell ions of their DMIM counterparts. Copyright © 2014 John Wiley & Sons, Ltd.     

Gas phase retro‐Michael reaction resulting from dissociative protonation: fragmentation of protonated warfarin in mass spectrometry

A mass spectrometric study of protonated warfarin and its derivatives (compounds 1 to 5) has been performed. Losses of a substituted benzylideneacetone and a 4‐hydroxycoumarin have been observed as a result of retro‐Michael reaction. The added proton is initially localized between the two carbonyl oxygens through hydrogen bonding in the most thermodynamically favorable tautomer. Upon collisional activation, the added proton migrates to the C‐3 of 4‐hydroxycoumarin, which is called the dissociative protonation site, leading to the formation of the intermediate ion‐neutral complex (INC). Within the INC, further proton transfer gives rise to a proton‐bound complex. The cleavage of one hydrogen bond of the proton‐bound complex produces the protonated 4‐hydroxycoumarin, while the separation of the other hydrogen bond gives rise to the protonated benzylideneacetone. Theoretical calculations indicate that the 1, 5‐proton transfer pathway is most thermodynamically favorable and support the existence of the INC. Both substituent effect and the kinetic method were utilized for explaining the relative abundances of protonated 4‐hydroxycoumarin and protonated benzylideneacetone derivative. For monosubstituted warfarins, the electron‐donating substituents favor the generation of protonated substituted benzylideneacetone, whereas the electron‐withdrawing groups favor the formation of protonated 4‐hydroxycoumarin. Copyright © 2012 John Wiley & Sons, Ltd.     

Gas‐phase basicity of 2‐furaldehyde

2‐Furaldehyde (2‐FA), also known as furfural or 2‐furancarboxaldehyde, is an heterocyclic aldehyde that can be obtained from the thermal dehydration of pentose monosaccharides. This molecule can be considered as an important sustainable intermediate for the preparation of a great variety of chemicals, pharmaceuticals and furan‐based polymers. Despite the great importance of this molecule, its gas‐phase basicity (GB) has never been measured. In this work, the GB of 2‐FA was determined by the extended Cooks's kinetic method from electrospray ionization triple quadrupole tandem mass spectrometric experiments along with theoretical calculations. As expected, computational results identify the aldehydic oxygen atom of 2‐FA as the preferred protonation site. The geometries of O‐O‐cis and O‐O‐trans 2‐FA and of their six different protomers were calculated at the B3LYP/aug‐TZV(d,p) level of theory; proton affinity (PA) values were also calculated at the G3(MP2, CCSD(T)) level of theory. The experimental PA was estimated to be 847.9 ± 3.8 kJ mol^?1, the protonation entropy 115.1 ± 5.03 J mol^?1 K^?1 and the GB 813.6 ± 4.08 kJ mol^?1 at 298 K. From the PA value, a ΔH°_f of 533.0 ± 12.4 kJ mol^?1 for protonated 2‐FA was derived. Copyright © 2012 John Wiley & Sons, Ltd.     

Photooxygenation and gas‐phase reactivity of multiply threaded pseudorotaxanes

The solution‐phase photooxygenation of multiply threaded crown/ammonium pseudorotaxanes containing anthracene spacers is monitored by electrospray ionization Fourier‐transform ion‐cyclotron‐resonance (ESI‐FTICR) mass spectrometry. The oxygenated pseudorotaxanes are mass‐selected and fragmented by infrared multiphoton dissociation (IRMPD) and/or collision‐induced dissociation (CID) experiments and and their behavior compared to that of the non‐oxygenated precursors. [4+2]Cycloreversion reactions lead to the loss of O₂, when no other reaction channel with competitive energy demand is available. Thus, the release of molecular oxygen can serve as a reference reaction for the energy demand of other fragmentation reactions such as the dissociation of the crown/ammonium binding motifs. The photooxygenation induces curvature into the initially planar anthracene and thus significantly changes the geometry of the divalent, anthracene‐spacered wheel. This is reflected in ion‐mobility data. Coulomb repulsion in multiply charged pseudorotaxanes assists the oxygen loss as the re‐planarization of the anthracene increases the distance between the two charges. Copyright © 2016 John Wiley & Sons, Ltd.     

Gas‐phase reactivity of 2‐hydroxy‐1,4‐naphthoquinones: a computational and mass spectrometry study of lapachol congeners

In order to understand the influence of alkyl side chains on the gas‐phase reactivity of 1,4‐naphthoquinone derivatives, some 2‐hydroxy‐1,4‐naphthoquinone derivatives have been prepared and studied by electrospray ionization tandem mass spectrometry in combination with computational quantum chemistry calculations. Protonation and deprotonation sites were suggested on the basis of gas‐phase basicity, proton affinity, gas‐phase acidity (ΔG_acid), atomic charges and frontier orbital analyses. The nature of the intramolecular interaction as well as of the hydrogen bond in the systems was investigated by the atoms‐in‐molecules theory and the natural bond orbital analysis. The results were compared with data published for lapachol (2‐hydroxy‐3‐(3‐methyl‐2‐butenyl)‐1,4‐naphthoquinone). For the protonated molecules, water elimination was verified to occur at lower proportion when compared with side chain elimination, as evidenced in earlier studies on lapachol. The side chain at position C(3) was found to play important roles in the fragmentation mechanisms of these compounds. Copyright © 2012 John Wiley & Sons, Ltd.     

Characterization of complex,heterogeneous lipid A samples using HPLC‐MS/MS technique III. Positive‐ion mode tandem mass spectrometry to reveal phosphorylation and acylation patterns of lipid A

In this study, we report the detailed analysis of the fragmentation patterns of positively charged lipid A species based on their tandem mass spectra obtained under low‐energy collision‐induced dissociation conditions of an electrospray quadrupole time‐of‐flight mass spectrometer. The tandem mass spectrometry experiments were performed after the separation of the compounds with a reversed‐phase high performance liquid chromatography method. We found that both, phosphorylated and nonphosphorylated lipid A molecules can be readily ionized in the positive‐ion mode by adduct formation with triethylamine added to the eluent. The tandem mass spectra of the lipid A triethylammonium adduct ions showed several product ions corresponding to inter‐ring glycosidic cleavages of the sugar residues, as well as consecutive and competitive eliminations of fatty acids, phosphoric acid, and water following the neutral loss of triethylamine. Characteristic product ions provided direct information on the phosphorylation site(s), also when phosphorylation isomers (ie, containing either a C1 or a C4′ phosphate group) were simultaneously present in the sample. Continuous series of high‐abundance B‐type and low‐abundance Y‐type inter‐ring fragment ions were indicative of the fatty acyl distribution between the nonreducing and reducing ends of the lipid A backbone. The previously reported lipid A structures of Proteus morganii O34 and Escherichia coli O111 bacteria were used as standards. Although, the fragmentation pathways of the differently phosphorylated lipid A species significantly differed in the negative‐ion mode, they were very similar in the positive‐ion mode. The complementary use of positive‐ion and negative‐ion mode tandem mass spectrometry was found to be essential for the full structural characterization of the C1‐monophosphorylated lipid A species.     

Formation and hydrolysis of gas‐phase [UO2(R)]+: R═CH3, CH2CH3, CH═CH2, and C6H5

The goals of the present study were (a) to create positively charged organo‐uranyl complexes with general formula [UO₂(R)]⁺ (eg, R═CH₃ and CH₂CH₃) by decarboxylation of [UO₂(O₂C─R)]⁺ precursors and (b) to identify the pathways by which the complexes, if formed, dissociate by collisional activation or otherwise react when exposed to gas‐phase H₂O. Collision‐induced dissociation (CID) of both [UO₂(O₂C─CH₃)]⁺ and [UO₂(O₂C─CH₂CH₃)]⁺ causes H⁺ transfer and elimination of a ketene to leave [UO₂(OH)]⁺. However, CID of the alkoxides [UO₂(OCH₂CH₃)]⁺ and [UO₂(OCH₂CH₂CH₃)]⁺ produced [UO₂(CH₃)]⁺ and [UO₂(CH₂CH₃)]⁺, respectively. Isolation of [UO₂(CH₃)]⁺ and [UO₂(CH₂CH₃)]⁺ for reaction with H₂O caused formation of [UO₂(H₂O)]⁺ by elimination of ·CH₃ and ·CH₂CH₃: Hydrolysis was not observed. CID of the acrylate and benzoate versions of the complexes, [UO₂(O₂C─CH═CH₂)]⁺ and [UO₂(O₂C─C₆H₅)]⁺, caused decarboxylation to leave [UO₂(CH═CH₂)]⁺ and [UO₂(C₆H₅)]⁺, respectively. These organometallic species do react with H₂O to produce [UO₂(OH)]⁺, and loss of the respective radicals to leave [UO₂(H₂O)]⁺ was not detected. Density functional theory calculations suggest that formation of [UO₂(OH)]⁺, rather than the hydrated U^VO₂⁺, cation is energetically favored regardless of the precursor ion. However, for the [UO₂(CH₃)]⁺ and [UO₂(CH₂CH₃)]⁺ precursors, the transition state energy for proton transfer to generate [UO₂(OH)]⁺ and the associated neutral alkanes is higher than the path involving direct elimination of the organic neutral to form [UO₂(H₂O)]⁺. The situation is reversed for the [UO₂(CH═CH₂)]⁺ and [UO₂(C₆H₅)]⁺ precursors: The transition state for proton transfer is lower than the energy required for creation of [UO₂(H₂O)]⁺ by elimination of CH═CH₂ or C₆H₅ radical.     

Gas‐phase Smiles Rearrangement of Sulfonylurea Herbicides in Electrospray Ionization Mass Spectrometry

In the negative ion mode of electrospray ionization tandem mass spectrometry (ESI‐MS/MS) of four sulfonylurea herbicides, Smiles rearrangements were observed in rimsulfuron and nicosulfuron. In the case of rimsulfuron, two competitive gas‐phase Smiles rearrangements initiated by nitrogen anion and oxygen anion respectively were witnessed. The ion‐neutral complex was proposed as the reactive intermediate in the course of this unimolecular dissociation reaction of the oxygen attack Smiles rearrangement route. The density functional theory (DFT) was carried out to elucidate the mechanism as well as to show the possible transition states and the intermediates.     

两类三组份反应产物：1,3-恶嗪及嘧啶-2-酮类化合物的质谱学行为研究

电喷雾质谱被应用于分辨2-氨基-1,3-恶嗪及六氢化-4-苯基-吡喃[2,3-d]嘧啶-2-酮的杂环结构。两类化合物均为三组份反应的产物,且其杂环的结构很难用NMR判断。实验首次系统研究了两类化合物的质谱学行为（包括氘代实验和高分辨质谱研究）,发现前者在CID实验中丢失CH2N2和HCNO,而后者为直接丢失尿素。这些特征丢失为该类衍生物的结构判断,尤其是高通量的合成产物分析提供了重要的依据。     

The unusual fragmentation of long‐chain feruloyl esters under negative ion electrospray conditions

Long‐chain ferulic acid esters, such as eicosyl ferulate ( 1 ), show a complex and analytically valuable fragmentation behavior under negative ion electrospay collision‐induced dissociation ((?)‐ESI‐CID) mass spectrometry, as studied by use of a high‐resolution (Orbitrap) mass spectrometer. In a strong contrast to the very simple fragmentation of the [M + H]⁺ ion, which is discussed briefly, the deprotonated molecule, [M – H]^?, exhibits a rich secondary fragmentation chemistry. It first loses a methyl radical (MS²) and the ortho‐quinoid [M – H – Me]^‐? radical anion thus formed then dissociates by loss of an extended series of neutral radicals, C_nH_2n + 1^? (n = 0–16) from the long alkyl chain, in competition with the expulsion of CO and CO₂ (MS³). The further fragmentation (MS⁴) of the [M – H – Me – C₃H₇]^? ion, discussed as an example, and the highly specific losses of alkyl radicals from the [M – H – Me – CO]^‐? and [M – H – Me – CO₂]^‐? ions provide some mechanistic and structural insights.     

Hypervalent radical formation probed by electron transfer dissociation of zwitterionic tryptophan and tryptophan‐containing dipeptides complexed with Ca2+ and 18‐crown‐6 in the gas phase

The relationship between peptide structure and electron transfer dissociation (ETD) is important for structural analysis by mass spectrometry. In the present study, the formation, structure and reactivity of the reaction intermediate in the ETD process were examined using a quadrupole ion trap mass spectrometer equipped with an electrospray ionization source. ETD product ions of zwitterionic tryptophan (Trp) and Trp‐containing dipeptides (Trp‐Gly and Gly‐Trp) were detected without reionization using non‐covalent analyte complexes with Ca²⁺ and 18‐crown‐6 (18C6). In the collision‐induced dissociation, NH₃ loss was the main dissociation pathway, and loss related to the dissociation of the carboxyl group was not observed. This indicated that Trp and its dipeptides on Ca²⁺(18C6) adopted a zwitterionic structure with an NH₃⁺ group and bonded to Ca²⁺(18C6) through the COO^? group. Hydrogen atom loss observed in the ETD spectra indicated that intermolecular electron transfer from a molecular anion to the NH₃⁺ group formed a hypervalent ammonium radical, R‐NH₃, as a reaction intermediate, which was unstable and dissociated rapidly through N–H bond cleavage. In addition, N–C_α bond cleavage forming the z₁ ion was observed in the ETD spectra of Trp‐GlyCa²⁺(18C6) and Gly‐TrpCa²⁺(18C6). This dissociation was induced by transfer of a hydrogen atom in the cluster formed via an N–H bond cleavage of the hypervalent ammonium radical and was in competition with the hydrogen atom loss. The results showed that a hypervalent radical intermediate, forming a delocalized hydrogen atom, contributes to the backbone cleavages of peptides in ETD. Copyright © 2015 John Wiley & Sons, Ltd.     

Development of resonance‐enhanced multiphoton ionization SNMS for state‐selective detection of sputtered atoms under low‐energy ion irradiation

An instrument for a sputtered neutral mass spectrometry with a quadrupole mass spectrometer (QMS) by resonance‐enhanced multiphton ionization method is developed to study sputtered neutrals emission phenomena under ion irradiation in a low‐energy region. We have prepared a pulsed primary ion beam and an ion counting system, and have optimized the operation parameter including a sample bias, energy analyzer voltages, pulsed timing of laser and ion beam, etc. A yield ratio of the lowest‐lying excited state a⁵S₂ to the ground state a⁷S₃ for sputtered Cr atoms has been measured as a function of incident energy of Ar⁺ and O₂⁺ down to 600 eV using a polycrystalline Cr sample. The yield ratio has become a constant value for the Ar⁺ incidence, while it has exponentially increased below 1 keV for the O₂⁺ incidence. It is found that the internal energy distribution of sputtered Cr atoms has been significantly influenced by oxygen density at the surface. Copyright © 2011 John Wiley & Sons, Ltd.     

Substitution reactions of gaseous ions in a three‐dimensional quadrupole ion trap

Substitution reactions between gaseous ions and neutral substrate molecules are of ongoing high interest. To investigate these processes in a qualitative and quantitative manner, we have constructed a device, with which a defined amount of a volatile substrate can be mixed with a defined amount of helium gas and added into a three‐dimensional quadrupole ion trap. From the known inner volume of the device, the known ratio n_substrate:n_He of the mixture, and the determined absolute partial pressure of helium in the ion trap, we can derive the partial pressure of the substrate in the ion trap and, thus, convert the directly observable pseudo–first‐order rate constants of the substitution reactions into absolute bimolecular rate constants. We have tested the device by investigating a series of S_N2 reactions of Br ^? and CF₃CH₂O ^? anions as well as ligand exchange reactions of ligated Na⁺ cations. As the obtained results suggest, the described device makes it possible to determine the bimolecular rate constants of substitution reactions as well as other ion‐molecule reactions with satisfactory accuracy and reliability.     

Negative ion electrospray high‐resolution tandem mass spectrometry of polyphenols

Representative compounds with a 1,3‐dihydroxybenzene substructure belonging to different important polyphenol classes (stilbenes, flavones, isoflavones, flavonols, flavanones, flavanols, phloroglucinols, anthraquinones and bisanthraquinones) were investigated based on detailed high‐resolution tandem mass spectrometry measurements with an Orbitrap system under negative ion electrospray conditions. The mass spectral behaviour of these compound classes was compared among each other not only with respect to previously described losses of CO, CH₂CO and C₃O₂ but also concerning the loss of CO₂ and successive specific fragmentations. Furthermore, some unusual fragmentations such as the loss of a methyl radical during mass spectral decomposition are discussed. The obtained results demonstrate both similarities and differences in their mass spectral fragmentation under MSⁿ conditions, allowing a characterization of the corresponding compound type. Copyright © 2015 John Wiley & Sons, Ltd.