Electron impact mass spectrometry of nuphar alkaloids. II—Thiohemiaminals

The appearance of m/e 228 and 176 ions, useful in ascertaining the presence of the hemiaminal hydroxyl, are discussed for six thiaspirane-type hemiaminals isolated from Nuphar luteum and three epimeric pairs of α-thiohemiaminals derived from (–)-deoxynupharidine. Other groups of ions useful in ascertaining stereochemical differences of the sulfur moiety in α-thiohemiaminals are discussed for the same compounds. One such group of ions is comprised of 248, 246 and 231; a second is 192 and 191.     

Stereochemical applications of mass spectrometry. II—Chemical ionization mass spectra of isomeric dicarboxylic acids and derivatives

The H₂ and CH₄, chemical ionization mass spectra of the cis dicarboxylic acids, maleic and citraconic acid, show much more extensive loss of H₂O from [MH]⁺ than the trans isomers, fumaric acid and mesaconic acid. Similarly, esters of maleic acid show a much more facile loss of ROH (R=alkyl or phenyl) from [MH]⁺ than do esters of fumaric acid. Similar differences are observed in the chemical ionization mass spectra of the isomeric phthalic and isophthalic acids and derivatives, where the ortho isomers show more extensive fragmentation of [MH]⁺ than the meta isomers. The facile fragmentation of [MH]⁺ for the cis and ortho isomers is attributed to ROH elimination involving interaction between the two carboxylate functions and forming the stable cyclic anhydride structure for the fragment ion. By contrast ROH elimination from [MH]⁺ for the trans and metu isomers requires a symmetry-forbidden [1,3]-H migration in the carboxyl protonated species and cannot lead to the cyclic anhydride structure. The chemical ionization mass spectra of cis and trans cyclohexane-1,2-dicarboxylic acids are essentially identical and show extensive fragmentation of the [IMH]⁺ ion. Experiments using deuterium labelling show extensive carboxyl group interactions for both isomers. The chemical ionization mass spectra of maleanilic and phthalanilic acids and of the related anhydrides and imides also are reported, as are the electron impact mass spectra of diphenyl maleate, diphenyl fumarate, diphenyl phthalate, maleanilic acid and phthalanilic acid.     

Tandem mass spectrometry of peptides: Mechanistic aspects and structural information based on neutral losses. II—Tri- and larger peptides

The neutral products arising during the collisionally activated dissociation of protonated oligopeptides (MH⁺) are post-ionized by collision and detected in neutral fragment-reionization (⁺N_fR⁺) mass spectra. For the isomeric tripeptides Ala-Gly-Gly, Gly-Ala-Gly and Gly-Gly-Ala, the amino acid and dipeptide losses from the C-terminus and the diketopiperazine losses from the N-terminus allow for differentiation. These neutral fragments are identified in the corresponding ⁺N_fR⁺ spectra by comparison to reference collision-induced dissociative ionization (CIDI) mass spectra of individual amino acids, dipeptides and diketopiperazines. Peptides with distinct C-termini but otherwise identical sequences are found to yield ⁺N_fR⁺ products that are characteristic of the respective C-terminal amino acid. This is demonstrated for several peptide pairs, including leucine- and methionine-enkephalin. In general, ⁺N_fR⁺ spectra are dominated by the heavier neutral losses; further, ⁺N_fR⁺ and CIDI cause extensive dissociation, indicating that the collisional ionization process imparts high average internal energies.     

Negative ions in organic mass spectrometry. II—Negative ion mass spectra of simple thio and dithio esters.

The 70 eV negative ion mass spectra of some simple aromatic and aliphatic thio and dithio esters are discussed. A characteristic fragmentation process, a rearrangement analogous to the nitro-nitrite conversion of aromatic nitro compounds, is observed for aromatic thio esters.     

Studies in mass spectrometry. II—A common intermediate in the primary fragmentation process of α-phenylmethylenecylopropane

The variation of Z = [(F)⁺]/[(M)^+·] vs electron energy for the loss of H^· and CH₃^· from the molecular ion of 2-phenylmethylenecyclopropane (I) and α-phenylmethylenecyclopropane (II) suggests that they both rearrange to a common intermediate before fragmentation occurs. The structure of the intermediate is discussed with regard to the xperimental values found for the Z ratios and to the mass spectra of deuterium labelled compounds.     

Application of mass spectrometry in silkworm research—Review

In this first mass spectrometry‐focused review paper, we will review current applications of mass spectrometry in the area of silkworm research. We will focus our review on the following two most important areas as they are currently being researched by scientists. Firstly, the proteomics of proteins in the process of silkworm lifecycle has generated knowledge about previous undetected proteins, some of which might possess therapeutic effects. Secondly, fatty acids, which are the other major components in silkworm, have several potential medical applications. We will also highlight potential areas warranting further investigation.     

Hydrogen migrations in mass spectrometry. II—single and double hydrogen migrations in the electron impact fragmentation of n-propyl benzoate

The sources of the migrant hydrogen atom(s) in reactions (a) and (b) in the electron impact mass spectrum of n-propyl benzoate have been investigated: (a) [C₆H₅CO₂C₃H₇]⁺ →[C₆H₅CO₂H]⁺ + C₃H₆; (b) [C₆H₅CO₂C₃H₇]⁺ → [C₆H₅CO₂H₂]⁺ + C₃H₅^sdot;. Deuterium labelling of the propyl group showed that, for reaction (a) at 70 eV ionizing energy 3 ± 1% of the hydrogen originates from C-1 of the propyl group, 86 ± 4% from C-2 and 11 ± 3% from C-3. The specificity of the transfer from C-2 increases as the internal energy of the fragmenting ions decreases, indicating that the results cannot be rationalized in terms of H/D interchanges between positions in the propyl group, but rather that the reaction involves specific, competing, H transfer reactions from each propyl position, in contrast to the high site specificity characteristic of the McLafferty rearrangement. Reaction (b) involves, almost exclusively, transfer of one hydrogen from C-2 and one from C-3 with only very minor participation of C-1 hydrogens. The [C₆H₅COOH]⁺ ion produced in reaction (a) fragments further to [C₆H₅CO]⁺ + OH. and the labelling results indicate some interchange of the carboxylic hydrogen with (ortho) ring hydrogens for those ions fragmenting in the first drift region. The extent of interchange is less than that observed for fragmentation of the same ion produced by direct ionization of benzoic acid or by reaction (a) in ethyl benzoate.     

Heuristic programming as an ion generator in mass spectrometry. II—Generation of primary ions from simple cyclic structures

The Ion Generator computer program has now the ability to fragment cyclic structures Examples of mechanisms which are proposed by the program for the fragmentation of simple ring compounds are presented.     

High resolution mass spectrometry. Bufadienolides—II.

Complete low resolution mass spectra and high resolution data for selected important peaks are presented and discussed for a series of naturally occurring 14β, 15β-epoxybufadienolides (toad poisons) and their derivatives. The compounds examined were resibufogenin, marinobufagin, cinobufagin, desacetylcinobufagin, cinobufotalin, desacetylcinobufotalin and resibufagin, and the derivatives were 11α-hydroxyresibufogenin, 3β-acetoxymarinobufagin, 3-ketocinobufagin, 3β-acetoxy-16β-desacetylcinobufagin, 3β-acetoxy-16-ketocinobufagin, resibufaginol, 14α-artebufogenin and 3β-suberyloxyresibufogenin methyl ester. The relatively unsaturated 2-pyrone group of C-17β has been used as an integral label to distinguish (from elemental composition data) ions containing it from those arising in other parts of the molecule that do not, and the spectra are interpreted in terms of structural ‘ion types’.     

Heterocyclic studies—XXX: Application of mass spectrometry to the study of covalent hydration

Comparison of the mass spectra of 3,4-hydrated 4-trifluoromethylpteridine derivatives with those of corresponding anhydrous compounds shows that this technique can be used to deduce the position of covalent hydration in heterocyclic compounds. It is less easy to demonstrate the presence of added water molecules in 5,6,7,8-dihydrated derivatives of ethyl pteridine-4-carboxylates, but spectra run at low ionising voltages give the required information. Two hydrates (3,4-hydrates of 4-ethoxycarbonyl- and 4-trifluoromethyl-pteridine-2(1H)-thione) which are very much more thermally stable than usual are also discussed. Metastable peaks and accurate mass measurements support many of the postulated fragmentation pathways.     

Reaction gas chromatography/mass spectrometry. 2—the use of catalytic on-line dehydrogenation for the investigation of alcohols by gas chromatography/mass spectrometry

A method for structure determination of aliphatic alcohols within mixtures is described. It involves the use of a vapour phase dehydrogenation micro-reactor (Cu, 300°C) located between the chromatographic column and the mass spectrometer or between the injection port and the column. Since primary and secondary alcohols are converted into corresponding carbonyl compounds, they can be readily differentiated from tertiary alcohols and dialkyl ethers. An examination of the mass spectra of alcohols and carbonyl compounds permits the determination of molecular mass, the location of hydroxyl group and the determination of branching at the β-carbon atom.     

Etude conformationnelle de la dimethyl-3,4 cyclopentanone trans: II—Spectres de RMN

The NMR spectra of trans-3,4-dimethylcyclopentanone and trans-3,4-dimethyl-2,2,5,5-tetradeuteriocyclopentanone are analysed. The coupling constants, calculated for the deuterated compound, are in good agreement with a diequatorial conformation of the methyl groups.     

Contributions of mass spectrometry to structural immunology

Mass spectrometry has made important contributions to the field of immunology in the past decade. A variety of mass spectrometric-based techniques have been applied to study the structures of macromolecules that play a vital role in the immune response. These include traditional molecular mass measurements to identify post-translational modifications and structural heterogeneity, mass mapping of proteolysis products, sequencing by tandem mass spectrometry and conformational analysis. Antigen-antibody and other immune complexes have been detected by mass spectrometry, providing an avenue to study macromolecular assemblies that are important to immune function. By virtue of the ability of mass spectrometry based techniques to analyze complex biological mixtures, mass spectrometry has also been employed to identify and sequence protein epitopes important in both the humoral and cellular immune responses. This has been achieved through a combination of immunoaffinity and mass spectrometric techniques, and the coupling of high-performance chromatographs to mass spectrometers. These approaches are important for the identification of pathogens and show promise for the early diagnosis of disease associated with viral and bacterial infection and malignancy. These investigations will enable the mechanisms associated with normal and impaired immune function to be elucidated. Mass spectrometry has been utilized to characterize the structure of peptide mimics, multiple antigenic peptides and other constructs in the design of synthetic immunogens. Information derived from these studies will aid in the development of novel therapeutics and vaccines.     

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.     

Application of mass spectrometry in structural and stereochemical investigations

The mass spectra of 3-acetoxy- and 3-benzoxy-substituted quinuclidines and benzo(b)quinuclidines were investigated. The fragmentation of the investigated compounds is realized from the open form of the molecular ion that is produced after cleavage of the bridge bond containing the substituents. Subsequent elimination of an acyl group leads to the formation of characteristic fragments, the peaks of which are the maximum-intensity peaks in the spectra.See [2] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1411–1417, October, 1972.     

Mass spectrometry in structural and Stereochemical problems—XXXVI Alkaloids of periwinkles—27; the mass spectra of stereo-isomers of the sarpagine-akuammidine group

Mass spectra have been measured of members of the sarpagine-akuammidine group differing in stereochemistry at C-16. Attention is called to possible fallacies in expecting analogous fragmentation behavior of closely related compounds (N_(a)—H vs. N_(a)—Me) if the mechanism of a specific fragmentation is not known. Attention is drawn to the structural information which can be gained from thermal decomposition processes prior to electron impact. The mutual advantages of an all-glass and a direct inlet system are discussed.     

Application of mass spectrometry in structural and stereochemical investigations

The mechanism of the process M⁺→(M-CO)⁺ during fragmentation, under the influence of electron impact, of some bicyclic amines with a nodal nitrogen atom and containing an oxo group in various positions of the bridged system is discussed. Data on the ionization potentials and low-voltage mass spectra and from high-resolution mass spectrometry are used.     

2,3,5,6-Tetramethylmorpholine: II—1H n.m.r. structural studies of the isomers of 2,3,5,6-tetramethylmorpholine

The structures of the six isomers of 2,3,5,6-tetramethyl-morpholine have been determined by means of proton nuclear magnetic resonance studies at 100 MHz. The spectra have been analysed in terms of spin–spin coupling constants and population distributions of the possible conformers at low temperatures. Also included in this paper are results from n.m.r. studies on the six 4-benzyl-2,3,5,6-tetramethylmorpholine derivatives, which give information about the stereochemistry of the methyl groups α to the amine group.     

Mass spectral studies of cycloheptatrienes. II—The monochlorocycloheptatrienes

The mass spectra of isomeric chlorocycloheptatrienes have been studied at high and low electron beam energies. Ion kinetic energy spectrometry was utilized to examine the major decomposition pathways. The extreme similarity found in the spectral characteristics of these compounds provides information about the structure of the decomposing molecular ion.