Ion-molecule reactions observed for nitroaromatic compounds in negative ion fast atom bombardment mass spectrometry

Analyses of a series of nitroaromatic compounds using fast atom bombardment (FAB) mass spectrometry are discussed. An interesting ion-molecule reaction leading to [M + O ? H]^? ions is observed in the negative ion FAB spectra. Evidence from linked-scan and collision-induced dissociation spectra proved that [M + O ? H]^? ions are produced by the following reaction: M + NO₂^? → [M + NO₂]^? → [M + O ? H]^?. These experiments also showed that M^?˙ ions are produced in part by the exchange of an electron between M and NO₂^? species. All samples showed M^?˙, [M ? H]^? or both ions in their negative ion FAB spectra. Not all analytes studied showed either [M + H]⁺ and/or M⁺˙ in the positive ion FAB spectra. No M⁺˙ ions were observed for ions having ionization energies above ～9 eV.     

[C]+· and [CH]+ from doubly charged ions formed from malononitrile

The metastable ions [M]²⁺, [M – H]²⁺· and [M – H₂]²⁺ from malononitrile fragment by loss of [CH]⁺, [C]⁺· and [C]⁺·, respectively. The reaction of the molecular ion involves the methylene and nitrile carbon atoms in the statistical probability ratio, while that of [M – H]²⁺· involves exclusively the nitrile carbon and that of [M ? H₂]²⁺ involves an approximately equal contribution, from both sources. It is suggested that the metastable molecular ion fragments through a bipyrimidal intermediate.     

A fast atom bombardment and field ionization/field desorption study of some isomeric unsaturated dicarboxylic acids

Geometrically isomeric dicarboxylic acids, such as maleic and fumaric acid and their methyl homologues, and the isomeric phthalic acids, have been investigated using fast atom bombardment, field ionization and field desorption mass spectrometry. The most intense peak in the positive ion fast atom bombardment spectra corresponds with the [M + H]⁺ ion. This ion, when derived from the E -acids, tragments either by successive loss of water and carbon monoxide or by elimination of carbon dioxide. In the case of the Z -acids only elimination of water from the [M + H]⁺ ions is observed to occur to a significant extent. The same is true for the [M + H]⁺ ions of the isomeric phthalic acids, that is the [M + H] ions derived from iso- and terephthalic acid exhibit more fragmentation than those of phthalic acid. All these acids undergo much less fragmentation upon field ionization, where not only abundant [M + H]⁺ ions, but also abundant [M]^+· ions, are observed. Upon field desorption only the [M + H]⁺ and [M + Na]⁺ ions are observed under the measuring conditions. Negative ion fast atom bombardment spectra of the acids mentioned have also been recorded. In addition to the most abundant [M? H]^? ions relatively intense peaks are observed, which correspond with the [M]^?˙ ions. The fragmentations observed for these ions appear to be quite different from those reported in an earlier electron impact study and in a recent atmospheric pressure ionization investigation.     

Differentiation of anomeric C-glycosides by mass spectrometry using fast atom bombardment,mass-analysed ion kinetic energy and collision-activated dissociation

Positive-ion fast atom bombardment mass spectrometry appears to be a useful method for the differentiation of anomeric C-glycosides. The mass-analysed ion kinetic energy (MIKE) and collision-activated dissociation (CAD) MIKE spectra of selected positive ions can be used as fingerprints of the α- or β-anomers. The main fragmentation routes and particularly the formation of the [M ? H]⁺ ion and the [M + H ? PhCH₂OH]⁺ ion were traced for each anomer.     

Fast atom bombardment mass spectra of telluronium salts

The fast atom bombardment (FAB) mass spectra of telluronium salts were studied. The spectra exhibit the intact cation (C⁺) and cluster ions ([M + C]⁺). The principal fragment ions in the FAB mass spectra of telluronium salts are [RTe]⁺, [R₂Te]⁺˙, [R₂Te − H]⁺, [RTeR′]⁺˙, and [RTeR′ + H]⁺. When the anion was [BPh₄]⁻, interesting cluster ions such as [M + C − BPh₃]⁺ appeared.     

Use of fast atom bombardment mass spectrometry for the characterization of nitroaromatic isomers

Positive and negative ion fast atom bombardment (FAB) mass spectra of some monosubstituted nitroaromatic isomers are reported. Generally ions carresponding to [M + H]⁺ and M⁺ are observed in the positive ion FAB spectra; ions such as [M ? H] ^? and M^?˙ are observed in the negative ion FAB spectra. The use of FAB mass spectra to distinguish the isomers is discussed. Comparisons of FAB, chemical ionization and electron impact mass spectra of the same isomers (wherever possible) are reported. The structural information obtained in the negative ion FAB spectra complement those obtained in the positive ion FAB spectra.     

Studies in chemical ionization mass spectrometry: 17-hydroxy steroids

The chemical ionization mass spectra of several hydroxy steroids were obtained using methane as the reactant gas. The spectra are much less complex than the electron ionization spectra and little fragmentation of the steroid nucleus is observed. The major fragment ions involve the loss of water from [M + H]⁺. A 3-keto group in the steroids was characterized by an abundant [M + C₂H₅]⁺ ion. 5α- and 5β-Dihydrotestosterone could be distinguished by their spectra, with H₂ as the reactant gas by marked differences in amounts of [M + H]⁺, [M + H ? H₂O]⁺ and [M + H ? 2H₂O]⁺. Substituted 3α-X-, 17 β-ol compounds, (X = Cl, Br) were also studied to obtain relative amounts of protonation at these sites.     

Electron impact mass spectra of polycyclic aromatic compounds with several types of pyridino- and benzobenzanthrone skeletons

Electron impact mass spectra were measured for five isomers of pyridinobenzanthrones and three isomers of benzobenzanthrones. The fragmentation pattern and intensity of M²⁺, [M – H]⁺, [M – CO]ⁱ⁺, [M – CO – H(or 2H)]ⁱ⁺ and [M – CO – HCN]ⁱ⁺ (i = 1, 2) ions indicated remarkable differences and very interesting features according to the isomers with or without nitrogen and condensation positions of a pyridino or benzo ring to the benzanthrone skeleton. Further, the competition of decompositions through [M – H]⁺, [M – CO]^+˙ or [M – HCN]^+˙ ions was confirmed by the observation of metastable ions and the appearance energies of fragment ions. Interesting observations from these results were expulsion of an H atom in close proximity to the area around an O?C group, a weak bonding interaction between sp² C? H and an O?C group, inducing specific hydrogen rearrangement, and characteristic charge localization on heteroatoms.     

Selective reagents in chemical ionization mass spectrometry: Tetramethylsilane with ethers

Chemical ionization mass spectra of several ethers obtained with He/(CH₃)₄Si mixtures as the reagent gases contain abundant [M + 73]⁺ adduct ions which identify the relative molecular mass. For the di-n-alkyl ethers, these [M + 73]⁺ ions are formed by sample ion/sample molecule reactions of the fragment ions, [M + 73 ? C_nH_2n]⁺ and [M + 73 ? 2CnH_2n]⁺. Small amounts of [M + H]⁺ ions are also formed, predominantly by proton transfer reactions of the [M + 73 ? 2CnH_2n]⁺ or [(CH₃)₃SiOH₂]⁺ ions with the ethers. The di-s-alkyl ethers give no [M + 73] ⁺ ions, but do give [M + H]⁺ ions, which allow the determination of the relative molecular mass. These [M + H]⁺ ions result primarily from proton transfer reactions from the dominant fragment ion, [(CH₃)₃SiOH₂]⁺ with the ether. Methyl phenyl ether gives only [M + 73]⁺ adduct ions, by a bimolecular addition of the trimethylsilyl ion to the ether, not by the two-step process found for the di-n-alkyl ethers. Ethyl phenyl ether gives [M + 73]⁺ by both the two-step process and the bimolecular addition. Although the mass spectra of the alkyl etherr are temperature-dependent, the sensitivities of the di-alkyl ethers and ethyl phenyl ether are independent of temperature. However, the sensitivity for methyl phenyl ether decreases significantly with increasing temperature.     

A 15N labelling,FD and FAB study of ammonia loss from protonated arginine molecules

The positive ion field desorption (FD) spectrum of arginine taken at the best anode temperature only contains a peak due to [M+H]⁺ ions. At higher emitter temperatures a considerable amount of fragmentation is induced and the [M+H NH₃]⁺ ions become most abundant. Specific ¹⁵N labelling reveals that the eliminated ammonia molecule, exclusively, contains one of the terminal nitrogen atoms of the guanidyl group. This also applies to the ammonia loss from metastably decomposing [M+H]⁺ ions. The positive ion fast atom bombardment (FAB) spectrum shows more fragmentation than the FD spectrum. In contrast with the FD results, the [M+H]⁺ ions generated upon FAB with ion lifetimes <10⁻⁶ s eliminate both ammonia containing one of the terminal nitrogen atoms of the guanidyl group and ammonia containing the α-amino group in the ratio of 1.35, as found by ¹⁵N labelling. The metastably decomposing [M+H]⁺ ions, however, eliminate only the former ammonia molecule. In the negative ion FD and FAB spectra no other peak than that corresponding to the [M H]⁻ ion is observed. Some attention has been paid to the thermal degradation of arginine on the basis of a few Curie-point pyrolysis experiments.     

Structural determination of modified fatty acids by collisional activation of cationized molecules

The nature and location of a variety of modifications of fatty acids are determined by collisional activation (CA) of [M + 2Li ? H]⁺ ions. The sample molecules are cationized in situ on the probe tip, desorbed by fast atom bombardment and, upon CA, undergo charge-remote decompositions. This approach is a direct, totally instrumental method for structure elucidation. Advantages of CA of [M + 2Li ? H]⁺ ions are that fatty acids with substituents in close proximity to the carboxylate terminus and modified short-chain acids are readily determined: decompositions of carboxylate anions of these fatty acids result in collision-activated dissociation (CAD) spectra that give incomplete structural information. However, the CAD spectra of some [M ? H]^? ions, such as those from epoxy acids, are simpler to interpret than those of the [M + 2Li ? H]⁺ ions. Thus, CA of fatty acid [M + 2Li ? H]⁺ ions is a complementary approach to CA of [M ? H]^? ions for determining the fatty acid structures investigated here. The use of this approach for analyzing complex mixtures of modified fatty acids is also evaluated.     

Relationships between structure,ionization profile and sensitivity of exogenous anabolic steroids under electrospray ionization and analysis in human urine using liquid chromatography–tandem mass spectrometry

The relationships between the ionization profile, sensitivity, and structures of 64 exogenous anabolic steroids (groups I–IV) was investigated under electrospray ionization (ESI) conditions. The target analytes were ionized as [M + H]⁺ or [M + H–nH₂O]⁺ in the positive mode, and these ions were used as precursor ions for selected reaction monitoring analysis. The collision energy and Q3 ions were optimized based on the sensitivity and selectivity. The limits of detection (LODs) were 0.05–20 ng/mL for the 64 steroids. The LODs for 38 compounds, 14 compounds and 12 compounds were in the range of 0.05–1, 2–5 and 10–20 ng/mL, respectively. Steroids including the conjugated keto‐functional group at C3 showed good proton affinity and stability, and generated the [M + H]⁺ ion as the most abundant precursor ion. In addition, the LODs of steroids using the [M + H]⁺ ion as the precursor ion were mostly distributed at low concentrations. In contrast, steroids containing conjugated/unconjugated hydroxyl functional groups at C3 generated [M + H ? H₂O]⁺ or [M + H ? 2H₂O]⁺ ions, and these steroids showed relatively high LODs owing to poor stability and multiple ion formation. An LC‐MS/MS method based on the present ionization profile was developed and validated for the determination of 78 steroids (groups I–V) in human urine. Copyright © 2015 John Wiley & Sons, Ltd.     

Mass spectra of sulfinamide derivatives and identification of their thermal decomposition products

The mass spectra of 30 sulfinamide derivatives (RSONHR', R' alkyl or p-XC₆H₄) are reported. Most of the spectra had peaks attributable to thermal decomposition products. For some compounds these were identified by pyrolysis under similar conditions to be: RSO₂NHR', RSO₂SR, RSSR and NH₂R' (in all kinds of sulfinyl amides); RSNHR' (in the case of arylsulfinyl arylamides); RSO₂C₆H₄NH₂, RSOC₆H₄NH₂ and RSC₆H₄NH₂ (in the case of arylsulfinyl arylamides of the type of X = H) The mass spectra of the three thermally stable compounds showed that there are several kinds of common fragment ions. The mass spectra of the thermally labile compounds had two groups of ions; (i) characteristic fragment ions of the intact molecules and (ii) the molecular ions of the thermal decomposition products. It was concluded that the sulfinamides give the following ions after electron impact: [M]⁺, [M ? R]⁺, [M ? R + H]⁺, [M ? SO]⁺, [RS]⁺, [NHR']⁺, [NHR' + H]⁺, [RSO]⁺, [RSO + H]⁺, [R]⁺, [R + H]⁺, [R']⁺ and [M ? OH]⁺, and that the thermal decomposition products give the following ions: [RSO₂SR]⁺, [RSSR]⁺, [M ? O]⁺, [M + O]⁺ and [RSOC₆H₄NH₂]⁺.     

Laser desorption mass spectrometry of squaric acid and its salts

The laser desorption mass spectrometry of the oxocarbon squaric acid (3,4-dihydroxy-3-cyclobutene-1,2-dione) and its salts of the form A₂C₄O₄ (A = cation) is described. Both positive and negative ion spectra were obtained. The positive ion spectrum of the acid is characterized by an ion corresponding to loss of CO from [M + H]⁺. The negative ion spectrum shows an intense [M ? H]^? peak in addition to a dimer species. The alkali salt spectra contain [M + A]⁺ in the positive mode and [M ? A]^? and an intense [C₄HO₄]^? in the negative mode. The smaller alkali salts also have an [M + H]⁺ adduct ion. Unlike the alkali squarates, the ammonium salt shows ions corresponding to losses of neutrals from the molecular adduct in the positive ion spectrum and a dimer species in the negative ion spectrum. Molecular weight information was obtained in all cases. A (bis) dicyanomethylene derivative of potassium squarate was also studied. Some field desorption mass spectrometry results are presented for comparison.     

HPLC‐DAD and HPLC‐ESI‐MS separation,determination and identification of the spin‐labeled diastereoisomers of podophyllotoxin

Spin‐labeled nitroxide derivatives of podophyllotoxin had better antitumor activity and less toxicity than that of the parent compounds. However, the 2‐H configurations of these spin‐labeled derivatives cannot be determined by nuclear magnetic resonance (NMR) methods. In the present paper, a high‐performance liquid chromatography‐diode array detection (HPLC‐DAD) and a high‐performance liquid chromatography‐electrospray ionization tandem mass spectrometry (HPLC‐ESI/MS/MS) method were developed and validated for the separation, identification of four pairs of diastereoisomers of spin‐labeled derivatives of podophyllotoxin at C‐2 position. In the HPLC‐ESI/MS spectra, each pair of diastereoisomers of the spin‐labeled derivatives in the mixture was directly confirmed and identified by [M+H]⁺ ions and ion ratios of relative abundance of [M‐ROH+H]⁺ (ion 397) to [M+H]⁺. When the [M‐ROH+H]⁺ ions (at m/z 397) were selected as the precursor ions to perform the MS/MS product ion scan. The product ions at m/z 313, 282, and 229 were the common diagnostic ions. The ion ratios of relative abundance of the [M‐ROH+H]⁺ (ion 397) to [M+H]⁺, [A+H]⁺ (ion 313) to [M‐ROH+H]⁺, [A+H‐OCH₃]⁺ (ion 282) to [M‐ROH+H]⁺ and [M‐ROH‐ArH+H]⁺ (ion 229) to [M‐ROH+H]⁺ of each pair of diastereoisomers of the derivatives specifically exhibited a stereochemical effect. Thus, by using identical chromatographic conditions, the combination of DAD and MS/MS data permitted the separation and identification of the four pairs of diastereoisomers of spin‐labeled derivatives of podophyllotoxin at C‐2 in the mixture.     

Hydrogen transfer in the retro diels–alder fragmentation of oxygen-containing heterocyclic compounds. II—Chromones

Mass Spectra of unsubstituted, 2-methyl-, 3-methyl and 2,3-dimethylchromones were examined. These compounds showed [RDA]⁺˙ and [RDA + H]⁺ ions as characteristc ions, together with [M? H]⁺,[M? CO]⁺˙,[M? CHO]⁺ and [RDA? CO]⁺˙ ions. Based on deuterium labelling experiments and measurement of metastable peaks by the ion kinetic energy defocusing technique, the origin of transferred hydrogen in the [RDA + H]⁺ ion was clarified. The mechanism of the [RDA + H]⁺ ion formation is discussed.     

Structural characterization of isomeric triazolocoumarins by high- and low-energy collision spectrometry of M+˙, [M + H]+ and [M − H]− species

Two monometayl- and four dimethyl-triazolocoumarin isomers were characterized by their electron impact mass spectra and by low-energy collision experiments performed on molecular ions M⁺˙ and other fragment ions with an ion-trap mass spectrometer. High-energy collision-activated dissociation measurements were performed on the protonated [M + H]⁺ and deprotonated [M ? H]^? molecular ion obtained by fast atom bombardment and M⁺˙ species produced by electron impact ionization on a double-focusing, reverse-geometry instrument. The data obtained allowed unequivocal structural identification of all the compounds investigated.     

Dimer formation in methane chemical ionization mass spectrometry of organic functionalities,including 2-azaadamantane derivatives

The methane chemical ionization mass spectra of 1-hydroxy-2-azaadamantane, its lactolactam, and 1-chloro-2-azaadamantanes exhibit high intensity dimeric species. These correspond to [2M+H]⁺ or stable fragments formed via gas phase chemical reactions, such as dehydration (aminol case) or dehydrohalogenation (chloroazaadamantanes). The tert-amino chloroazaadamantane forms a stable [2M+C₂H₅]⁺ ion with much higher intensity than the [2M+H]⁺ ion. Similar dimeric species were observed with simple functionalities, including amide, amine, alcohol and alkene. Pressure, temperature and, apparently, steric effects play important roles. Structures are proposed for the various dimeric ions.     

Fast atom bombardment (FAB) mass spectrometry of piperidine N-oxide derivatives and free radical quenching under FAB conditions

Mechanisms are proposed for the formation of M⁺, [M + 2H]⁺ and [M + 3H]⁺ ions in the fast atom bombardment (FAB) mass spectra of 4-(2,2,6,6-tetramethyl-1-oxyl)-piperidol and its carboxylates. Free radical quenching induced by the fast atom beam has been observed. The effects of temperature on the radical quenching and of acid on the FAB mass spectra are discussed. The experiment showed that the volatile liquid samples with vapour pressures higher than that for glycerol produced M⁺ even-electron molecular ions, and the FAB mass spectra were similar to the corresponding electron ionization mass spectra. For the solid samples, it was found that the free radicals were quenched during the FAB process so that the mononitroxide and dinitroxide compounds produced [M + 2H]⁺ and [M + 3H]⁺ ions, respectively. Further experiments showed that the intensities and stabilities of [M + 2H]⁺ and [M + 3H]⁺ ions could be improved by addition of acids.     

Fast atom bombardment mass and tandem mass spectra of protonated and alkali cationized aldobiouronic and pseudoaldobiouronic acid per-O-methyl derivatives

The positive-ion fast atom bombardment mass spectra of permethylated aldo- and pseudoaldobiouronic acids can be used to distinguish these classes of compounds. The collisional-induced dissociation spectra of the [M + H]⁺ ions show fragment ions resulting from glycosidic bond cleavage and successive losses of methanol molecules. These spectra together with those of the [M + H ? MeOH]⁺ oxonium ions allow the identification of the type of interglycosidic linkage. Collisional activation of the relatively stable [M + Na]⁺ ions show many fragmentations which are common to alkali cationized permethylated saccharides. Moreover, fragment ions resulting from two-bond ring cleavage processes yield additional information with respect to the linkage between the hexose and uronic acid units.