Understanding the fragmentation of glucose in mass spectrometry

The fragmentation mechanism of D-glucose was investigated in detail by two different fragmentation techniques, namely, collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) using all six ¹³C-labeled isotopomers and ²H-labeled isotopomers. For both CID and IRMPD energy-resolved measurements were carried out. Individual fragmentation pathways were studied at MS² and MS³ levels. Additionally, we have developed an HPLC-tandem MS method to separate the anomers of D-glucose using a HILIC column and investigated their fragmentation patterns individually. We propose a complete fragmentation landscape of D-glucose, demonstrating that a rather simple multifunctional molecule displays extreme complexity in gas phase dissociation, following multiple parallel fragmentation routes yielding a total of 23 distinct fragment ions. The results allowed a detailed formulation of the complex fragmentation mechanism of D-glucose. The results have immediate consequences for the full structure analysis of complex carbohydrates.     

Electron ionization mass spectrometric study of substituted alloxazine‐5‐oxides and iso‐alloxazine‐5‐oxide

The fragmentation pathways in electron ionization (EI) mass spectra of a series of new N(5)‐oxides of alloxazines and iso‐alloxazine are presented, and compared with those of substituted alloxazines and iso‐alloxazine. The EI mass spectra of these compounds showed characteristic fragmentation pathways A, B and C, started by the ejection of atomic oxygen, a HNCO molecule and an OH ^. radical, respectively. On the basis of B/E and B²/E spectra, the mechanism of elimination of the OH ^. radical is discussed. The influence of the methyl substituent in the benzene ring of alloxazine on the mass fragmentation pathways is described. Copyright © 2009 John Wiley & Sons, Ltd.     

Ortho effects in organic molecules on electron impact. Part 16. Novel oxygen transfers from the nitro group to acetylenic carbons in 2-nitrodiphenylacetylenes

Oxygen transfers to both acetylene carbons are noticed in parallel fragmentation pathways during the electron impact induced decompositions of 2-nitrodiphenylacetylene. The oxygen transfer to β-acetylenic carbon leads to the most abundant ion corresponding to benzoyl cation while transfer to the α-acetylenic carbon affords less intense fragments corresponding to [M? OH]⁺, [M? CO]^{+ ˙} and [M? CO₂]^{+ ˙}. The proposed fragmentation pathways and ion structures are supported by high-resolution data, linked-scan spectra and chemical substitution.     

Fragmentation of deprotonated cyclic dipeptides by electrospray ionization mass spectrometry

The fragmentation pathways of deprotonated cyclic dipeptides have been studied by electrospray ionization multi‐stage mass spectrometry (ESI‐MSⁿ) in negative mode. The results showed that the fragmentation pathways of deprotonated cyclic dipeptides depended significantly on the different substituents, the side chains of amino acid residues at the diketopiperazine ring. In the spectra of deprotonated cyclic dipeptides, the ion [M? H? substituent radical]^? was firstly observed in the ESI mode. The characteristic fragment ions [M? H? substituent radical]^? and [M? H? (substituent? H)]^? could be used as the symbols of particular cyclic dipeptides. The hydrogen/deuterium (H/D) exchange experiment, the high‐resolution mass spectrometry (Q‐TOF) and theoretical calculations were used to rationalize the proposed fragmentation pathways and to verify the differences between the fragmentation pathways. The relative Gibbs free energies (ΔG) of the product ions and possible fragmentation pathways were estimated using the B3LYP/6–31++G(d, p) model. The results have some potential applications in the structural elucidation and interpretation of the mass spectra of homologous compounds and will enrich the gas‐phase ESI‐MS ion chemistry of cyclic dipeptides. Copyright © 2009 John Wiley & Sons, Ltd.     

Fragmentation Pathways of Singly- and Doubly-charged Ions in the Mass Spectra of Si-, N- and C-Substituted 1,3-Dioxa-6-aza-2-silacyclooctanes

The fragmentation pathways of singly- and doubly-charged ions in the mass spectra of Si-, N-, and C-substituted 1,3-dioxa-6-aza-2-silacyclooctanes upon electron impact have been studied. The directions for the fragmentation of the singly- and doubly-charged molecular ions differ markedly. All the doubly-charged fragmentation ions are formed by the loss of neutral molecules from M⁺⁺ and contain nitrogen and silicon atoms.     

Investigation of azoles and azines. 76. Mass spectra of 5- and 6-substituted uracils

Peaks of molecular ions that generally have the maximum intensity are observed in the mass spectra of most of the investigated 5- and 6-substituted uracils and 5-substituted orotic acids and their deutero analogs and methylated derivatives. The principal pathway of the fragmentation of the molecular ions is retrodiene fragmentation with the formation of [O=C₍₄₎C₍₅₎R⁵C₍₆₎R₍₆₎N₍₁₎R¹]⁺ (F₁) ions. The stabilities of the latter depend on the nature and position of the substituents attached to the C₍₅₎ and C₍₆₎ atoms. The fragmentation of the F₁ ions can be realized via four principal pathways (B-E) with the detachment of N-CR⁶ (B), O=C=CR⁵ (C), CO (D), and R⁶ (E) fragments. The most general pathway for the fragmentation of 5-substituted uracils is pathway C, whereas the most general pathway for 6-substituted uracils is pathway E. In the spectra of 5-substituted orotic acids the intensities of the molecular-ion peaks are high (100%) only in the case of electron-donor R⁵ and decrease sharply with an increase in the electron-acceptor strength of the substituent. The principal pathways of fragmentation of the molecular ions are decarboxylation (F) and retrodiene fragmentation (A), the contribution of which is appreciably smaller. The M-CO₂ ions formed after decarboxylation undergo fragmentation via a scheme similar to that observed for 5-substituted uracils.See [1] for Communication 75.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 520–531, April, 1990.     

Quantum chemical mass spectrometry: ab initio prediction of electron ionization mass spectra and identification of new fragmentation pathways

The electron ionization mass spectra of four organic compounds are predicted based on the results of quantum chemical calculations at the DFT/B3LYP/6‐311 + G* level of theory. This prediction is performed ‘ab initio’, i.e. without any prior knowledge of the thermodynamics or kinetics of the reactions under consideration. Using a set of rules determining which routes will be followed, the fragmentation of the molecules' bonds and the complete resulting fragmentation pathways are studied. The most likely fragmentation pathways are identified based on calculated reaction energies ΔE when bond cleavage is considered and on activation energies ΔE^? when rearrangements are taken into account; the final intensities of the peaks in the spectrum are estimated from these values. The main features observed in the experimental mass spectra are correctly predicted, as well as a number of minor peaks. In addition, the results of the calculations allow us to propose fragmentation pathways new to empirical mass spectrometry, which have been experimentally verified using tandem mass spectrometry measurements. Copyright © 2016 John Wiley & Sons, Ltd.     

二肽衍生物的电喷雾质谱研究

基于HIV整合酶核心结构域,合成了以HIV整合酶为靶标的二肽衍生物,采用多级质谱技术（二级、三级）研究二肽衍生物在质谱条件下的化学键断裂途径,发现主要的断裂方式为：氨基与羰基间的NH-CO键的断裂以及N-(苯并噻唑-2-基)甲酰氨基与亚甲基间的CO-C间的断裂。     

Ortho effects in organic molecules on electron impact: 19—Competing oxygen transfers from nitro group to sulphur and acetylinic carbons in 2-nitrophenylphenylethynylsulphides

Oxygen transfers to both the acetylenic carbons and sulphur are noticed in parallel fragmentation pathways during the electron-impact induced decompositions of 2-nitrophenylphenylethynylsulphides. Single oxygen transfer to acetylinic carbons leads to the most abundant ion corresponding to the benzoyl cation whilst double oxygen transfers to both the acetylenic carbons followed by the ejection of two CO units from the M⁺˙ ion afford another abundant fragment corresponding to the phenothiazine radical cation. However, the oxygen transfers to sulphur yield a less abundant [M ? SO₂H]⁺ ion. The proposed fragmentation pathways and the ion structures are sup ported by high-resolution data, collision-induced dissociation Linked-scan spectra and chemical substitution.     

Mass spectra of chlorinated aromatics formed in pulp bleaching 2—Chlorinated guaiacols

The fragmentation of chlorinated guaiacols (2-methoxyphenols) on electron impact has been studied. The most common fragmentation processes are interpreted and in some cases the small differences between spectra of positional isomers are explained. In addition to the well-known alkyl-oxygen fission (loss of methyl radical), metastable ion studies and deuterium labelling have indicated several new fragmentation pathways. The most characteristic are the formation of [M? CH₃? HCl]⁺ and [M? CH₃? Cl]^+· ions. In general, however, the spectra of positional isomers are shown to be very similar.     

Mass spectra of acyl and α-hydroxyalkyl derivatives of biferrocene

The mass spectral fragmentation pathways of acyl and α-hydroxyalkyl derivatives of biferrocene and related compounds are presented. A substituent effect for the cleavage of the cyclopentadienyl ring-metal bonds has been found in the spectra of acyl derivatives. It has been shown that the fragmentation of α-hydroxyalkyl derivatives proceeded via the ions corresponding to the [M]⁺? ions of oxidation or hydrogenolysis products of the hydroxyl derivatives.     

The electron impact fragmentation of 3- and 4-styrylpyridazine

The electron impact mass spectrometric fragmentation of trans-3- and trans-4-styrylpyridazine is reported in detail, including a comparison with other aza-stilbenes. With regard to a distinction between the two isomeric styrylpyridazines, the intensity ratio of the M⁺ and [M-1]⁺ ions, the general degree of fragmentation and the elimination pathways of nitrogen proved to be most characteristic.     

Investigation of fragmentation behaviors of steroidal drugs with Li+, Na+, K+ adducts by tandem mass spectrometry aided with computational analysis

In this study, we have investigated the fragmentation of the widely used steroidal pharmaceutical drugs (n = 14), complexed by a singly charged proton or alkali metal ion (Li⁺, Na⁺, K⁺) using Ion trap and quadrupole time-of-flight mass spectrometers. Spectra were collected by LC-MS/MS analysis using system automated collision energy i.e., of 25–60 eV. Theoretical calculations were also calculated using DFT software. The metal complexes showed different fragmentation pathways not commonly observed for protonated compounds. There was a distinct difference observed in the relative intensities of some common fragments for free vs. metallated drugs. Some major fragments from protonated and lithium adducts showed close resemblance, while sodium and potassium adducts showed different fragments. Theoretical calculations showed a distinct difference in the position of attachment of proton and metals. This adducts ion fragmentation information will be helpful for the identification of these compounds in complex samples.     

Synthesis and properties of azoles and their derivatives. 25. Electron-impact mass spectra of nitro- and nitroalkyl-substituted 3-aryl-δ2-isoxazolines

The fragmentation of nitro and nitroalkyl derivatives of 3-aryl-²-isoxazolines under the influence of electron impact was investigated. It was established that the fragmentation of the molecular ions of these compounds takes place primarily through the nitro- and halogen-containing groups; other pathways of dissociative ionization include the most important pathways of the fragmentation of arylisoxazoles.See [1] for Communication 24.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 980–983, July, 1990.     

Mass spectra and structures of isomeric phenylaminopyrazoles

The processes involved in the dissociative ionization of isomeric phenylaminopyrazoles under the influence of electron impact were studied. The pathways of fragmentation of the molecular ion (M⁺) were proved rigorously by means of the spectra of the metastable ions. The empirical compositions of the fragment ions were confirmed by the high-resolution mass spectra. It was established on the basis of the mass spectra of the amino-group-deuterated analogs that M⁺ exists exclusively in the amide from. A rearrangement leading to the formation of benzodiazepine cation radicals precedes fragmentation of M⁺. The elimination of an HCN particle in the first step of the fragmentation of M⁺ does not involve the amino group. The pK_a values are presented for all of the investigated phenylaminopyrazoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1381–1388, October, 1978.     

A mass spectrometric study of dimethyl ester trimethylsilyl ether derivatives of some 3-hydroxydicarboxylic acids

The fragmentation pathways for the dimethyl ester trimethylsilyl ether derivatives of some 3-hydroxydicarboxylic acids have been found by using B/E 2nd B²/E linked scans and isotope substitution techniques. Most of the fragments are due to ionization at silicon, which induces a fragmentation pattern that intimately reflects the structure of the compounds.     

Mass spectral fragmentation pathways in some glycoluril-type explosives. A study by collision-induced dissociation and isotope labeling

Electron impact (EI), chemical ionization and negative-ion chemical ionization (NCI) mass spectra of 1,4-dinitroglycoluril (DINGU), its ¹⁵N- and ²H-labeled analogues and the dimethyl-substituted derivatives were recorded. Tandem mass spectrometry with collision induced dissociation was used to study the fragmentation pathways of these compounds. It was found that the main EI fragmentation processes of DINGU are due to the cleavage of C? N bonds and some rearrangement reactions.     

Effects of Alkali Metal Ion Cationization on Fragmentation Pathways of Triazole-Epothilone

The collisionally activated dissociation mass spectra of the protonated and alkali metal cationized ions of a triazole-epothilone analogue were studied in a Fourier transform ion cyclotron resonance mass spectrometer. The fragmentation pathway of the protonated ion was characterized by the loss of the unit of C₃H₄O₃. However, another fragmentation pathway with the loss of C₃H₂O₂ was identified for the complex ions with Na⁺, K⁺, Rb⁺, and Cs⁺. The branching ratio of the second pathway increases with the increment of the size of alkali metal ions. Theoretical calculations based on density functional theory (DFT) method show the difference in the binding position of the proton and the metal ions. With the increase of the radii of the metal ions, progressive changes in the macrocycle of the compound are induced, which cause the corresponding change in their fragmentation pathways. It has also been found that the interaction energy between the compound and the metal ion decreases with increase in the size of the latter. This is consistent with the experimental results, which show that cesiated complexes readily eject Cs⁺ when subject to collisions.     

Mass spectral fragmentation pathways in 2,4,6-trinitrotoluene derived from a MS/MS unimolecular and collisionally activated dissociation study

The fragmentation pathways of 2,4,6-trinitrotoluene have been examined using ¹⁵N and ²H isotopic labelling in conjunction with tandem mass spectrometry. Both the unimolecular and collisionally activated decomposition modes were investigated. Fragmentation pathways were established in both modes and isotopic shifts were used to determine the groups lost. The major pathways include the loss of OH or H₂O, followed by the subsequent loss of NO or NO₂. There is virtually no ring disintegration until the majority of the attached groups are lost.     

Fragmentation studies of neutral per- and polyfluoroalkyl substances by atmospheric pressure ionization-multiple-stage mass spectrometry

The establishment of fragmentation pathways has a great interest in the identification of new or unknown related compounds present in complex samples. On that way, tentative fragmentation pathways for the ions generated by atmospheric pressure ionization of neutral per- and polyfluorinated alkyl substances (PFASs) have been proposed in this work. Electrospray (ESI), atmospheric pressure chemical ionization (APCI) and photoionization (APPI) were evaluated using mobile phases and source conditions that enhance the ionization efficiency of ions generated. A hybrid mass spectrometer consisting of a linear ion trap and an Orbitrap was used to combine the information of both multiple-stage mass spectrometry (MSⁿ) and mass accuracy measurements to characterize and establish the genealogical relationship between the product ions observed. The ionization mechanisms to generate ions such as [M–H]⁻, [M]^−•, and [M+O₂]^−• or the in-source collision-induced dissociation (CID) fragment ions in each API source are discussed in this study. In general, fluorotelomer olefins (FTOs) ionized in negative-ion APCI and APPI generated the molecular ion, while fluorotelomer alcohols (FTOHs) also provided the deprotonated molecule. Besides, fluorooctane sulfonamides (FOSAs) and sulfonamido-ethanols (FOSEs) led to the deprotonated molecule and in-source CID fragment ions, respectively. The fragmentation pathways from these precursor ions mainly involved initial α,β-eliminations of HF units and successive losses of CF₂ units coming from the perfluorinated alkyl chain. Moreover, FTOHs and FOSEs showed a high tendency to generate adduct ions under negative-ion ESI and APPI conditions. The fragmentation study of these adduct ions has demonstrated a strong interaction with the attached moiety.

Graphical abstract