An overview of the retro-Diels-Alder reaction in semiunsaturated heterocyclic rings: mass spectra of new substituted 1,4,5,6,7,8-hexahydroquinolines and their oxo-analogues 5,6,7,8-tetrahydro-4H-chromenes

Electron impact ionization (EI), chemical ionization (CI), electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) were used to investigate a number of relatively large and structurally related new heterocycles such as substituted 1,4,5,6,7,8-hexahydroquinolines and their oxa-analogues 5,6,7,8-tetrahydro-4H-chromenes. In the EI spectra the hexahydroquinolines undergo the loss of the substituent attached at the C4 position, while the 4H-chromenes undergo a retro-Diels-Alder reaction (RDA) after elimination of the C4 substituent. Under chemical ionization conditions the RDA reaction is observed only for the 4H-chromenes. The ESI-MS/MS spectra reveal results similar to the EI and CI spectra, since the 4H-chromenes undergo RDA reactions while the hexahydroquinolines form a very stable even-electron pyridium ion derived from the loss of the C4 substituent.     

有机磷化合物的质谱研究(Ⅺ)——1,3,2—二氮磷杂环戊烷衍生物的化学电离质谱

本文报道了11种1,3,2-二氮磷杂环戊烷衍生物的化学电离质谱(CIMS),对热不稳定的化合物采用了解吸化学电离技术(DCI),着重探讨了三价磷和五价磷化合物质谱的差异及均三氮苯取代基的引入对质谱行为的影响;对该类化合物的CIMS和EIMS进行了比较。     

Comparison of electron and chemical ionization modes by validation of a quantitative gas chromatographic-mass spectrometric assay of new generation antidepressants and their active metabolites in plasma

A gas chromatographic-mass spectrometric method (GC-MS) for the simultaneous determination of the 'new' antidepressants (mirtazapine, viloxazine, venlafaxine, trazodone, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine) and their active metabolites (desmethylmirtazapine, O-desmethylvenlafaxine, m-chlorophenylpiperazine, desmethylcitalopram, didesmethylcitalopram, desmethylmianserin, desmethylfluoxetine, desmethylsertraline, desmethylmaprotiline) in plasma using different ionization modes was developed and validated. Sample preparation consisted of a strong cation exchange mechanism and derivatisation with heptafluorobutyrylimidazole. The GC separation was performed in 24.8 min. Identification and quantification were based on selected ion monitoring in electron (EI) and chemical ionization (CI) modes. Calibration by linear and quadratic regression for electron and chemical ionization, respectively, utilized deuterated internal standards and a weighing factor 1/x(2). Limits of quantitation were established between 5 and 12.5 ng/ml in EI and positive ionization CI (PICI), and 1 and 6.25 ng/ml in negative ionization CI (NICI). During validation stability, sensitivity, precision, accuracy, recovery, and selectivity were evaluated for each ionization mode and were demonstrated to be acceptable for most compounds. While it is clear that not all compounds can be quantitated either due to chromatographic (trazodone) or derivatisation problems (O-desmethylvenlafaxine), this method can quantitate most new antidepressants (ADs) in the therapeutic range using EI. PICI and NICI lead to higher selectivity. Moreover, NICI is of interest for small sample volumes and high sensitivity requirements. This paper draws the attention to the pros and cons of the different ionization modes in the GC-MS analysis of these antidepressants in plasma.     

Differentiation of diastereomeric conduramine derivatives under electron ionization and chemical ionization mass spectral conditions

Diastereomeric conduramine derivatives, i.e., (1R,2S,3R/S,6S)-6-(N-carbomethoxyamino) 1,2-O-isopropylidenecyclohex-4-ene-1,2,3-triol (1 and 2) and their O-acetyl derivatives (3 and 4), were studied using gas chromatography (GC) with electron ionization (EI) and chemical ionization (CI). The EI mass spectra of diastereomeric pairs show consistent differences in the relative abundances of characteristic ions. The EI fragmentation patterns are based on precursor/product ion spectra, high-resolution mass spectrometry (HRMS) and deuterium labelling. The CI spectra show differences from the EI spectra, and the isobutane/CI spectra are much simpler than the methane/CI spectra. The differences shown in the CI spectra are similar to those shown in the product ion spectra of [M+H](+) ions generated under electrospray ionization (ESI) conditions. Theoretical calculations are performed to understand the observed differences. The differences in the relative stabilities of molecular ions, or protonated molecules at different sites, can explain the observed differences in the spectra.     

Mass spectral characteristics of okadaic acid and simple derivatives.

Electron ionization (EI), chemical ionization (CI) and fast-atom bombardment (FAB) mass spectra of the marine toxin okadaic acid and its synthetic methyl, pentafluorobenzyl, and trimethylsilyl ester and ether derivatives were generated. Several ionization conditions and ion-processing methods were used to obtain positive- and negative-ion conventional spectra and tandem (MS/MS) spectra. The EI and the positive-ion CI spectra provided fragment ions characteristic of the structure, and the negative-ion CI and FAB spectra provided molecular ions. The addition of alkali salts to the FAB matrix resulted in reduced fragmentation and the formation of intense alkali-metal-cationized molecules. Pentafluorobenzyl ester derivatives provided intense carboxylate ions under electron-capture ionization. Analytically useful MS/MS spectra were obtained by low-energy collision-induced decomposition of the carboxylate anion produced from the tetrasilylated pentafluorobenzylokadaate.     

Electron impact and chemical ionization mass spectra of 2,2-diphenyl-3-arylcyclobutanone oximes. Formation of ion m/z 167

The electron impact (EI) and chemical ionization (CI) spectra of 2,2-diphenyl-3-aryl cyclobutanone oximes (1–5) are reported. Formation of diphenylmethyl cation at m/z 167 is a major fragmentation process in both EI and CI spectra. Labelling studies established that the hydrogen involved in this rearrangement transfers from the NOH group and not from cyclobutane ring positions. The [M + 3]⁺ ions are formed under CI conditions as a result of C?N double bond reduction. An interesting secondary kinetic isotope effect is observed in the formation of ion e at m/z 183 in both EI and CI spectra. Other characteristic fragmentation pathways occurring in the EI and CI spectra of these compounds are outlined.     

Chemical ionization and electron impact mass spectra of symmetrical S-alkyl alkanesulfonothioates (thiosulfonates)

The chemical ionization (CI) and electron impact (EI) mass spectra of eight symmetrical S-alkyl alkanesulfonothioates (thiosulfonates) are reported.     

Determination of triazine herbicides in surface and drinking waters by off-line combination of liquid chromatography and gas chromatography-mass spectrometry

Summary Mass spectra of 12 triazines were obtained by electron impact (EI), positive-ion chemical ionization (PCI) and negative-ion chemical ionization (NCI) using methane and isobutane as reagent gases. EI mass spectrometry is more sensitive than PCI and NCI, although the chemical ionization modes increase selectivity markedly. A pre-column packed with polymer stationary phase was employed to preconcentrate surface and drinking water samples. After desorption of the analytes with ethyl acetate, an aliquot was injected directly into the GC-MS system. Atrazine and simizine were found in these samples at 10–80 ppt levels. The limits of detection for both herbicides were below 10 ppt in drinking water.     

The effects of electron and chemical Ionization Modes on the MS Profiling of Whole Bacteria

Free fatty acid profiling of whole bacteria [Francisella tularensis, Brucella melitensis, Yersinia pestis, Bacillus anthracis (vegetative and sporulated), and Bacillus cereus] was carried out with direct probe mass spectrometry under 70-eV electron ionization (EI) and isobutane chemical ionization in both the positive (CI+) and negative modes (CI-). Electron ionization produced spectra that contained molecular ions and fragment ions from various free fatty acids. Spectra acquired with isobutane chemical ionization in the positive mode yielded molecular ions of free fatty acids as well as ions from other bacterial compounds not observed under EI conditions. Spectra obtained with negative chemical ionization did not contain as much taxonomic information as EI or CI+; however, some taxonomically significant compounds such as dipicolinic acid and poly(3-hydroxybutyrate) did produce negative ions. All ionization modes yielded spectra that could separate the bacteria by Gram-type when observed with principle components analysis (PCA). Chemical ionization in the positive ion mode produced the greatest amount of differentiation between the four genera of bacteria when the spectra where examined by PCA.     

Electron ionization and chemical ionization mass spectra of pyridinium and isoquinolinium ylides

Electron ionization (EI) spectra and both positive and negative chemical ionization (CI) spectra have been obtained for four isoquinolinium ylides and two pyridinium ylides. Electron transfer reactions dominate the CI mass specra. The base peak in negative chemical ionization is the [M]^?· ion, formed by electron capture. In the positive methane CI spectra the molecular ion, [M]^+·, is relatively more intense than [MH]⁺ showing electron transfer to be the main positive ionization process. In the positive ammonia CI spectra, proton transfer to give [MH]⁺ is the main ionization process, but electron transfer is also observed. The EI spectra show fragmentations in which the aromatic nitrogen moiety retains the charge and fragmentation is by loss of radicals or small neutral molecules from the side-chains. Radical driven reactions are proposed to explain these spectra.     

Mass spectra of new substituted 2-amino-4H-pyrans: a retro-Diels-Alder reaction pattern

New substituted 2-amino-3-cyano-4H-pyrans have been studied by electron ionization (EI), chemical ionization (CI) and electrospray ionization (ESI) mass spectrometry. The retro-Diels-Alder reaction (RDA) is the main fragmentation pattern observed in the EI spectra forming an unsaturated ketone as the diene fragment. In contrast, a different RDA reaction takes place yielding an unsaturated amide as diene fragment together with the unsaturated ketone in the CI spectra. The MS/MS spectra obtained using an ESI source reveal that the favoured fragmentation by collision induced dissociation (CID) is the elimination of the substituent at the C4 position with formation of a stable pyrilium cation.     

Direct mass spectrometric analysis of Bacillus spores

Spores from the Bacillus species, B. cereus, B. anthracis, B. thuringensis, B. lichenformis, B. globigi, and B. subtilis, were examined by direct probe mass spectrometry using electron ionization (EI) and positive and negative chemical ionization (CI). Molecular ions from free fatty acids and nucleic acids were observed in the 70eV spectra as were fragments from glycerides. Spectra obtained with isobutane positive chemical ionization (CI(+)) were dominated by ions associated with pyranose compounds such as N-acetylglucosamine (NAG). Unlike the positive ion spectra, the negative ion spectra of the spores were very simple and contained few peaks. The M(-.) ion from dipicolinic acid (DPA) was the base peak in the negative ion spectra of all spore species except those from B. lichenformis. The negative ion of DPA produced such a strong signal that 10(8) colony forming units (CFUs) of B. cereus spores could be detected directly in 0.5 g of ground rice. Principal component analysis (PCA) of the spectra revealed that only CI(+) spectra contained differences that could be used to identify the spectra by species. Differentiation of the CI(+) spectra by PCA was attributed to variances in the peaks associated with the bacterial polymer poly(3-hydroxybutyrate) (PHB) and NAG. Similar differences in PHB and NAG peaks were detected in the CI(+) spectra of a suite of vegetative Bacillus stains grown with various media.     

Structural elucidation of disinfection by-products in treated drinking water

Two unusual disinfection by-products have been detected periodically in the gas chromatography/mass spectrometry (GC/MS) characterization analyses of semi-volatile organics in treated drinking water. The electron ionization (EI) mass spectra contained mono-chlorinated and mono-brominated ions at m/z 107/109 and 151/153, respectively. Library searching techniques suggested mono-halogenated butanol structures but no matches could be found. Positive ion chemical ionization (CI) spectra contained mono-chlorinated and mono-brominated ions at m/z 105/107 and 149/151, respectively. No [M + H]+ ions were initially observed. Accurate mass measurements confirmed the empirical formulae for the significant ions in the EI spectra and the mono-halogenated butanol structures. Further CI experiments with other reagent gases and instruments revealed possible molecular weights of 139 and 183 Da, respectively. Tandem mass spectrometry (MS/MS) experiments in EI and CI were used to elucidate the fragmentation schemes. The two compounds have been tentatively identified as 1-aminoxy-1-chlorobutan-2-ol and 1-aminoxy-1-bromobutan-2-ol, respectively.     

Gas chromatography-mass spectrometry with supersonic molecular beams

Gas chromatography-mass spectrometry (GC-MS) with supersonic molecular beams (SMBs) (also named Supersonic GC-MS) is based on GC and MS interface with SMBs and on the electron ionization (EI) of vibrationally cold analytes in the SMBs (cold EI) in a fly-through ion source. This ion source is inherently inert and further characterized by fast response and vacuum background filtration capability. The same ion source offers three modes of ionization including cold EI, classical EI and cluster chemical ionization (CI). Cold EI, as a main mode, provides enhanced molecular ions combined with an effective library sample identification, which is supplemented and complemented by a powerful isotope abundance analysis method and software. The range of low-volatility and thermally labile compounds amenable for analysis is significantly increased owing to the use of the contact-free, fly-through ion source and the ability to lower sample elution temperatures through the use of high column carrier gas flow rates. Effective, fast GC-MS is enabled particularly owing to the possible use of high column flow rates and improved system selectivity in view of the enhancement of the molecular ion. This fast GC-MS with SMB can be further improved via the added selectivity of MS-MS, which by itself benefits from the enhancement of the molecular ion, the most suitable parent ion for MS-MS. Supersonic GC-MS is characterized by low limits of detection (LOD), and its sensitivity is superior to that of standard GC-MS, particularly for samples that are hard for analysis. The GC separation of the Supersonic GC-MS can be improved with pulsed flow modulation (PFM) GC x GC-MS. Electron ionization LC-MS with SMB can also be combined with the Supersonic GC-MS, with fast and easy switching between these two modes of operation.     

Positive chemical ionization mass spectra of polycyclic chlorinated pesticides

Methane chemical ionization (CI) mass spectra for a series of ten polycyclic chlorinated insecticides and metabolites have been examined. In all cases except heptachlor epoxide the base peak corresponded to elimination of Cl, or OH from the molecule ion. In the spectrum of heptachlor epoxide the [M + H]⁺ and [M ? Cl]⁺ clusters were of approximately equal intensity. The CI spectra were remarkably simple, invariably less complex than the corresponding electron-impact (EI) mass spectra and the intensity of the ions with high information content, e.g. [M ? CI]⁺ was uniformly high. All of these features are important to the analytical potential of these studies. Retro Diels-Alder (RDA) fragments were observed for the chlordanes, aldrin, isodrin, nonachlor and heptachlor epoxide. The reported preliminary data suggest that the relative intensity of RDA ions in CI mass spectra may be useful in establishing molecular configurations.     

Cluster chemical ionization for improved confidence level in sample identification by gas chromatography/mass spectrometry

Upon the supersonic expansion of helium mixed with vapor from an organic solvent (e.g. methanol), various clusters of the solvent with the sample molecules can be formed. As a result of 70 eV electron ionization of these clusters, cluster chemical ionization (cluster CI) mass spectra are obtained. These spectra are characterized by the combination of EI mass spectra of vibrationally cold molecules in the supersonic molecular beam (cold EI) with CI-like appearance of abundant protonated molecules, together with satellite peaks corresponding to protonated or non-protonated clusters of sample compounds with 1-3 solvent molecules. Like CI, cluster CI preferably occurs for polar compounds with high proton affinity. However, in contrast to conventional CI, for non-polar compounds or those with reduced proton affinity the cluster CI mass spectrum converges to that of cold EI. The appearance of a protonated molecule and its solvent cluster peaks, plus the lack of protonation and cluster satellites for prominent EI fragments, enable the unambiguous identification of the molecular ion. In turn, the insertion of the proper molecular ion into the NIST library search of the cold EI mass spectra eliminates those candidates with incorrect molecular mass and thus significantly increases the confidence level in sample identification. Furthermore, molecular mass identification is of prime importance for the analysis of unknown compounds that are absent in the library. Examples are given with emphasis on the cluster CI analysis of carbamate pesticides, high explosives and unknown samples, to demonstrate the usefulness of Supersonic GC/MS (GC/MS with supersonic molecular beam) in the analysis of these thermally labile compounds. Cluster CI is shown to be a practical ionization method, due to its ease-of-use and fast instrumental conversion between EI and cluster CI, which involves the opening of only one valve located at the make-up gas path. The ease-of-use of cluster CI is analogous to that of liquid CI in ion traps with internal ionization, and is in marked contrast to that of CI with most other standard GC/MS systems that require a change of the ion source.     

Field desorption mass spectrometry of amino acids

The mass spectra of some amino acids have been studied using the field desorption method. All amino acids yield molecular or quasi-molecular ions, even in the case of arginine and cystine, where these ions cannot be detected with the electron-impact (EI) or chemical ionization (CI) methods. The fragmentation is reduced as compared to EI, CI and FI.     

Pyrolysis/chemical ionization mass spectrometry of polymers

Pyrolysis/mass spectrometric studies have been made on polystyrene, poly(vinyl chloride), and poly(methyl methacrylate) with electron ionization (EI) and chemical ionization (CI) mass spectrometry and a variable temperature probe for direct insertion into the source of the mass spectrometer. Similar results obtained with EI and CI mass spectrometry are in agreement with previous experiments. Advantages of the simplification of spectra in the CI made, as well as the advantages of using both techniques for identification of pyrolysis products, are discussed.     

Differentiation of diastereomeric N-aryltetrahydropyrano/tetrahydrofuranochromenylamines under electron ionization and chemical ionization conditions

A series of diastereomeric 4S,5S,6R/S-tetrahydropyrano- and 3S,4S,5R/S-tetrahydrofuranochromenylamine derivatives (a/b isomers; 1-26) has been studied under electron ionization (EI) and chemical ionization (CI) conditions. The EI mass spectra of all diastereomeric compounds show two characteristic fragment ions, of which one is formed by retro-Diels-Alder (RDA) reaction from the molecular ion, retaining the charge on the diene fragment, and the other [M-(HNAr)]+ ion by a simple radical loss. The RDA process is more favorable in all b isomers, whereas the radical loss is dominant in all a isomers; based on these two ions it is easy to differentiate the two diastereomers. The collision-induced dissociation (CID) spectra of all the molecular ions also show the same trend, which reflects the stereoselectivity in the formation of the two characteristic fragment ions. The results of theoretical calculations performed are in accordance with the experimental observations. The CI experiments (methane and isobutane) on all the diastereomeric compounds also enabled the differentiation of the isomers.     

Mass spectra of some new 3,4-dihydro-2[H]-pyridones

Electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) experiments, as well as electronic impact (EI) and chemical ionization (CI) techniques, have been applied to the title compounds 1a-h. The observation of different fragmentation pathways in the three sets of spectra is in accord with different degrees of internal excitation of the investigated precursors. In ESI (methanol as solvent) and CI (methane as reagent gas) spectra, the MH(+) ion represents the most important peak, while the fragments [M - OH](+) and [M - SO](+) are either the base peak or a very abundant peak in the EI mass spectra of these compounds. ESI-MS/MS experiments on the parent ions [MH](+) show that the loss of a fragment of 140 Da corresponding to p-toluenesulfenic acid is common from all the precursors. As well as competitive pathways, the second generation ions have also been elucidated to allow some observations to be made concerning the relationships between structure type and mass spectrometric characteristics.