Ammonia chemical ionization mass spectrometry of alcohols: Structural,stereochemical, molecular-size and temperature effects

Ammonia chemical ionization (CI) mass spectra of various open-chain, cyclic and unsaturated C₅- to C₁₀-alcohols were obtained at source temperatures ranging from 60° to 250°C. The reactivity of the ammonia adduct ion MNH and its fragmentation channels are characteristic for substrate structure. Although strongly temperature-dependent, the spectra give nevertheless information on the OH-group environment as well as on the C-skeleton at any source temperature. Primary, secondary and tertiary alcohols as well as allylic and simple olefinic alcohols can be distinguished by their spectra, which show ammonium adduct ions [MNH₄]⁺, adduct dehydrogenation ions [MNH₄-H₂], ammonium substitution ions [MNH₄-H₂O]⁺ and [M-OH]⁺-ions as the main characteristic peaks. Moreover, konfigurational assignments of stereoisomeric alcohols are possible for larger substrate-size and source-temperature ranges than with isobutane CI mass spectrometry. Homologous M NH-ions show molecular-size control of fragmentation and linear MNH-ions are less stable than branched isomers due to incomplete energy randomization.     

Control of the regiospecific synthesis of dialkylpyrrolizidinones and their stereochemical behaviour using gas chromatography/mass spectrometry with chemical ionization

Pyrrolizidine alkaloids were synthesized via the cyclization of an epoxide prepared from a lactam. The regiospecific control of this reaction is demonstrated using gas chromatography/mass spectrometry. Ammonia chemical ionization mass spectrometry permits the determination of the cis–trans stereochemistry of the final products.     

Electron and chemical ionization mass spectrometry in stereochemical differentiation of some 1,3-amino alcohols

Mass spectral fragmentations of two cyclopentane, eight cyclohexane and four norbornane/one 1,3-amino alcohols were studied under electron ionization (EI) by low-resolution, high-resolution, metastable ion analysis and collision-induced dissociation (CID) techniques. All stereoisomeric compounds gave rise to identical 70 eV EI mass spectra. However, the spectra of positional isomers clearly differed. The main fragmentation pathway for the saturated compounds began as an α-cleavage reaction with respect to the nitrogen atom. For the norbornene compounds a retro-Diels—Alder reaction was favoured. Relative to the aminomethyl-substituted compounds the fragmentation patterns for the compounds having the amino group connected directly to the ring were more complicated. The chemical ionization (CI) mass spectra were recorded using ammonia, isobutane, methane, dichloromethane and acetone as reagent gas. From the norbornane/One compounds the di-exo isomers decomposed more easily than the di-endo isomers with most of the reagent gases used. Differences between stereoisomers were observed directly only under methane CI. The decomposition products of the [M + H]⁺ ions generated under ammonia and isobutane CI were studies by recording their CID mass spectra. These spectra allowed the differentiation of the stereoisomers, at least to some extent.     

Atmospheric pressure chemical ionization negative mass spectra of the dinitrotoluene isomers

The atmospheric pressure chemical ionization of the dinitrotoluene isomers in ambient air was studied with a quadrupole mass spectrometer operating in the negative mode. The isomers can be grouped on the basis of the product ions: 2,5-, and 2,6- and 3,5-dinitrotoluene give the molecular anion with little fragmentation; 2,3- and the 3,4-dinitrotoluene behave similarly but with more extensive fragmentation; 2,4-dinitrotoluene gives the quasimolecular [DNT ? H]^? ion with little fragmentation. The results are discussed in terms of the molecular structure of the isomers.     

Analysis of 7-methylguanine using isotope dilution and gas chromatography/electron-capture negative chemical ionization mass spectrometry

This paper presents results obtained for in vivo endogenous and exogenous 7-methylguanine (7-MG) analyzed using a method incorporating gas chromatography with electron-capture negative chemical ionization mass spectrometry and isotope dilution (GC/EC-ID-MS). 13C4-Labeled 7-MG was synthesized to serve as an internal standard to improve accuracy of quantitation, and was used to analyze 7-MG in livers of control mice and dacarbazine-treated mice. The results confirm that 7-MG in tissue DNA can be measured using this GC/EC-ID-MS method with excellent sensitivity and specificity. Administration of 0, 30, and 60 mg/kg dacarbazine to mice led to dose-dependent increases in the formation of 7-MG. The results indicate that this method could be applied to the analysis of endogenous and exogenous 7-MG in human tissues for future molecular epidemiology studies on potential health effects caused by methylating agents.     

Pyrolysis mass spectrometry of terephthalate polyesters using negative ionization

The usual method of studying thermal degradation mechanisms of polymers in vacuo is to use electron ionization pyrolysis mass spectrometry. This can lead to mass spectral fragmentation from the 70 eV electrons used. Low energy electrons (10–15 eV) produce a low abundance of positive ions. However, if a molecule is prone to capture a thermal energy electron, then negative ions are produced in high abundance. This report describes the negative ion pyrolysis mass spectrometry of polyethylene terephthalate and polybutylene terephthalate.     

Stereochemical effects in the chemical ionization mass spectra of cyclic diols

The chemical ionization mass spectra of configurational isomers of many cyclic diols give substantial differences which are characteristic of their stereochemistry. For the cis-isomer of 1,3- and 1,4-cyclohexanediols, formation of a stable intramolecular proton bridge involving the OH groups gives rise to dominant MH⁺ peaks, suppressing the (M-H)⁺ peaks found in the spectra of the trans-isomers and monoalcohols. The stability of the proton bridge in cis-1,3-cyclohexanediol structures is decreased by a sterically interfering cis-5-methyl substituent, but increased by a cis-5-OH group due to additional proton solvation. cis-Stereochemistry also gives increased formation of the dimeric M₂H⁺ ions, but decreased formation of trimers, at higher diol concentrations, for the 1,3- and 1,4-diols. The similarity of the CI spectra of cis- and trans-1,2-cyclohexanediol are explicable in terms of the similarities of the most stable proton-bridged conformers; the reduced ring flexibility in cis- and trans-1,2-cyclopentanediols makes such similar structures unfavorable, as shown by the substantial differences between their CI spectra. The substantial, but expected, variations in behavior with temperature and reagent gas are useful for maximizing stereochemical effects on CI spectra; conditions of lowest energy are usually, but not always, the most useful.     

Interlaboratory comparison of limits of detectic in negative chemical ionization mass spectrometry

Data are presented on the limits of detection for a series of nine compounds in negative chemical ionization (NCI) mass spectra obtained in five different mass spectrometers: Finnigan 4000 with a 4500 ion source, Kratos MS-80, Hewlett-Packard 5985 and two Finnigan 4500s. The nine compounds undergo either resonance capture or dissociative capture of an electron at optimum energies ranging from 0.0 to 1.1 eV. The limits of detection generally increased with increasing optimum electron energy. The limit of detection as a function of optimum electron capture energy is expected to provide information about the electron energy distribution in the ion sources. The data showed scatter within and between instruments. The scatter is believed to be due primarily to reactions with low levels of adventitious gases such as oxygen in the ion source. The data also suggested wide variations in electron energies between the instruments. The variation in the electron energy distribution is thought to have been caused by variations in the ion optical fields within the instruments. These results suggest that the requirements for reproducibility in NCI mass spectra at the limit of detection are rigorous control of trace gases in the ion source, control of the electric fields within the source including ion optical fields that penetrate the source aperture control of pressure, temperature and other factors that influence NCI mass spectra.     

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.     

Stereochemical effects in mass spectrometry. 3—Detection of chirality by chemical ionization mass spectrometry

It was found that the chemical ionization mass spectra of the enantiomers of some α-amino acids and α-hydroxy acids could be definitely distinguished when a chiral compound, l-amyl alcohol, was used as a component of the reagent gases. The relative abundances of some characteristic ions produced through ion-molecule reactions in the gas phase were much higher in the D isomers than in the L isomers. The results were highly reproducible. This approach proved to be a convenient way for the detection of the chirality of these compounds by chemical ionization mass spectrometry.     

Inverse stereochemical effects in the mass spectra of carboalkoxycyclopropylsilanes

The electron impact induced decomposition of the cis and trans isomeric pairs of five 1-trialkylsilyl-2-alkoxy-carbonylcyclopropanes were investigated. Compared with carbon analogues, the silicon atom inhibited ring opening and dramatically altered the fragmentation. The main primary decomposition routes were alkyl loss from silicon, and trialkylsilyl ion formation as well as trialkylalkoxysilane elimination. An unexpected inverse stereochemical effect was found for this latter reaction which was far less significant for the cis isomers, where the interacting SiQ₃ and OR groups are close to each other, than for the trans isomers. This is explained by assuming a hidden silicon-oxygen bond formation, which is possible only in the cis isomers for geometric reasons. This interaction favours alkyl elimination over other fragmentations, and has a marked effect on the further decomposition of the [M—alkyl]⁺ ions, where observed differences in abundance as great as three orders of magnitude are accounted for.     

Positive desorption chemical ionization/tandem mass spectrometry of natural isomeric morphinans: Regioselectivity of protonation,positional and stereochemical effects upon decomposition

Fragmentations of naturally occurring morphinan isomers have been studied using a triple quadrupole mass spectrometer. Protonated molecules were generated via desorption chemical ionization using ammonia and methane as reagent gases. Mechanistic analysis of conformationally specific and stereospecific decomposition pathways has been performed and corroborated using deuterium labelling. Strong evidence of regioselective protonation has been offered, suggesting significant differences in the distribution of protonation sites as a function of reagent gas proton affinity.     

A derivatization assay using gaschromatography/negative chemical ionization tandem mass spectrometry to quantify 3-nitrotyrosine in human plasma

Endogenous free or protein-associated 3-nitrotyrosine (3-NT) has been proposed as a biomarker of in vivo oxidative damage caused by nitrating agents. Isotopic dilution assay gaschromatographic/mass spectrometric (GC/MS) techniques have been employed to measure endogenous 3-NT levels. However, the quantitative normal plasma values reported so far are inconsistent. The results vary between the assays; they may have been influenced by in vitro artifactual nitration of tyrosine to 3-NT. In this study, a simple and artifact-free derivatization method for quantifying the endogenous 3-NT content of biological samples by GC/negative chemical ionization MS/MS is presented. The method is based on reduction of the nitro group of the molecule by dithionite, heptafluorobutyric acylation and subsequent methyl derivatization, di-O-methyldi-N-heptafluorobutyryl being the major derivative. The results showed excellent GC and MS properties, such as low background and a favorable fragmentation pattern. Endogenous 3-NT was unequivocally quantified using collision-induced dissociation in the selected reaction monitoring mode, whereas co-elution of unknown compounds interfered in the selected-ion monitoring mode. We found that tyrosine was nitrated in the presence of nitrate anions and heptafluorobutyric anhydride, but the product appeared as a di-O-methylmono-N-heptafluorobutyryl derivative. Therefore, artifactually formed 3-NT did not contribute to the measured endogenous 3-NT level owing to its different derivative structure. The method was applied to determine endogenous 3-NT in human plasma and plasma proteins. A detection limit of 0.03 nM for (13)C(6)-labeled 3-NT in plasma samples was established and the response was linear over a concentration range of 0-50 nM (R(2) > 0.999). The endogenous free 3-NT level (mean +/- SD) in ultrafiltered plasma samples from 12 healthy adults was 0.74 +/- 0.30 nM. The mean concentration of 3-NT in their plasma total proteins was 0.60 +/- 0.40 pmol mg(-1). Hence, the described method is selective, eliminates the problem of artifactual nitration and is feasible for the quantification of free and protein-associated 3-NT in biological samples such as plasma.     

Hydrogen migrations in mass spectrometry. VI—the chemical ionization mass spectra of substituted benzoic acids and benzyl alcohols

The H₂ and CH₄ chemical ionization mass spectra of a series of series of substituted benzoic acids and substituted benzyl alcohols have been determined. For the benzoic acids the major fragmentation reactions of the protonated molecule involve elimination of H₂O or elimination of CO₂, the latter reaction involving migration of the carboxylic hydrogen to the aromatic ring. For the benzyl alcohols the major fragmentation reactions of [MH]⁺ involve loss of H₂O or CH₂O, analogous to the CO₂ elimination reaction for the benzoic acids. It is shown that the CO₂ and CH₂O elimination reactions occur only when a conjugated aromatic ring system is present, and that for the carboxylic acid systems, methyl groups and, to a lesser extent, phenyl groups are capable of migrating. The only discernible effect of substituents on the fragmentation of [MH]⁺ is an enhancement of the H₂O loss reaction in the benzoic acid system when an amino, hydroxyl, or halogen substituent is ortho to the carboxyl function. This ‘ortho’ effect, which differs in scope from that observed in electron impact mass spectra, is attributed to an intramolecular catalysis by the ortho substituent of the 1,3 hydrogen migration in the carbonyl protonated acid followed by H₂O elimination. Apparently, this route is favoured over the direct elimination of H₂O from the carbonyl protonated acid, since the latter has a high activation energy barrier because of unfavourable orbital symmetry restrictions.