Mass spectrometry of aryl substituted di- and trisiloxanes

The mass spectra of arylpentamethyldisiloxanes, sym-diaryltetramethyldisiloxanes and 1,5-diaryl-1,1,3,3,5,5-hexamethyltrisiloxanes were examined. Isotopic labeling and peak matching were used to substantiate the proposed fragmentation mechanisms. Siliconium ions dominate the spectra. Loss of neutral fragments from the [M-15]⁺ ions is important. Phenylpentamethyldisiloxane, sym-tetramethyldiphenyldisiloxane and 1,1,3,3,5,5-hexamethyl-1,5-diphenyltrisiloxane are representative examples of the three classes of compounds discussed. The [M-15]⁺ ion of phenylpentamethyldisiloxane loses methane, dimethylsilanone [(CH₃)₂Si?O] and phenylmethylsilanone [PhCH₃Si?O] to yield daughter siliconium ions. The [M-15]⁺ ion of sym-tetramethyldiphenyldisiloxane loses benzene, methane, dimethylsilanone and phenylmethylsilanone to yield daughter siliconium ions. The [M-15]⁺ ion of 1,1,3,3,5,5-hexamethyl-1,5-diphenyltrisiloxane loses benzene, tetramethylcyclodisiloxane and phenyltrimethylcyclodisiloxane to yield daughter siliconium ions. Finally, doubly charged ions are important in the mass spectra of the three series of aryl substituted di- and trisiloxanes discussed.     

Mass Spectral fragmentation patterns of heterocycles. V . Electron impact promoted mass spectral fragmentation of indolo[1,7-ab][1]benzazepine and Some of its Derivatives

The fragmentation patterns of 1,2,6,7-tetrahydroindolo[1,7-ab][l]benzazepin-1-one ( 1 ), 6,7-dihydroindolo-[1,7-ab][l]benzazepine ( 2 ) and indolo[1,7-ab][1]benzazepine ( 3 ) on electron impact have been examined. Loss of carbon monoxide to form the base peak at m/e 207 and loss of CHO radical to give m/e 206 consititute the major fragmentation pathways for 1. The moleclar ions ( M ⁺) are abundant for each of the compounds; observed as the second most intense peak for 1 (85% relative intensity) and the base peaks for 2 and 3 . The spectrum of 2 is characterized by intense M-1 and M-2 ions and by the presence of a M-15 ion (m/e 204) of moderate intensity (11.4%). In all other respects the spectra of 2 and 3 are strikingly similar. The M-15 ion from 2 , assigned the heteroaromatic pyrroloacridinium structure, is also formed in the spectrum of 1. A second heteroaromatic ion at m/e 191, common to the spectra of 1 , 2 and 3 , is believed to have the pyrrolocarbazol-ium structure. Metastable ion transitions and exact mass measurements support most of the proposed fragmentation pathways and structural assignments.     

Anion-π interactions—interactions between benzo-crown ether metal cation complexes and counter ions

The loss of X^· radical from [M + Cu + X]⁺ ions (copper reduction) has been studied by the so called in-source fragmentation at higher cone voltage (M = crown ether molecule, X⁻ = counter ion, ClO₄⁻, NO₃⁻, Cl⁻). The loss of X^· has been found to be affected by the presence/lack of aromatic ring poor/rich in electrons. Namely, the loss of X^· occurs with lower efficiency for the [NO₂-B15C5 + Cu + X]⁺ ions than for the [B15C5 + Cu + X]⁺ ions, where NO₂-B15C5 = 3-nitro-benzo-15-crown-5, B15C5 = benzo-15-crown-5. A reasonable explanation is that Anion-π interactions prevent the loss of X^· from the [NO₂-B15C5 + Cu + X]⁺ ions. The presence of the electron-withdrawing NO₂ group causes the aromatic ring to be poor in electrons and thus its enhances its interactions with anions. For the ion containing the aromatic ring enriched in electrons, namely [NH₂-B15C5 + Cu + ClO₄]⁺ where NH₂-B15C5 = 3-amino-benzo-15-crown-5, the opposite situation has been observed. Because of Anion-π repulsion the loss of X^· radical proceeds more readily for [NH₂-B15C5 + Cu + X]⁺ than for [B15C5 + Cu + X]⁺. Iron reduction has also been found to be affected by Anion-π interactions. Namely, the loss of CH₃O^· radical from the ion [B15C5 + Fe + NO₃ + CH₃O]⁺ proceeds more readily than from [NO₂⁻B15C5 + Fe + NO₃ + CH₃O]⁺.     

Mass spectra of new heterocycles: XI. Fragmentation of 5-(methylsulfanyl)-1-[2-(vinyloxy)ethyl]-1H-pyrrol-2-amines under electron impact and chemical ionization

Fragmentation patterns of the molecular ions of 5-(methylsulfanyl)-1-[2-(vinyloxy)ethyl]-1H-pyrrol- 2-amines generated by electron impact (70 eV) and chemical ionization (methane as reagent gas) were studied for the first time. The electron impact mass spectra of all the examined compounds showed abundant molecular ions whose subsequent fragmentation followed three main pathways: elimination of EtS radical, elimination of methyl radical from the MeS group, and cleavage of the C-N and/or C-C bonds which is accompanied by rearrangement processes. Further decomposition of the [M - EtS]⁺ ion is determined by the structure of the amino group. The chemical ionization mass spectra displayed strong molecular and [M + H]⁺ ion peaks together with representative series of fragment ion peaks. Unlike electron impact, the main decomposition pathway under chemical ionization is elimination of methylsulfanyl radical from the [M + H]⁺ ion to give abundant [M + H — MeS]⁺ ion.     

Mass-spectrometric study of ring-chain tautomerism in a series of substituted 4-hydroxyhexahydropyrimidine-2-thiones

In order to investigate the ring-chain tautomerism of substituted 4-hydroxyhexahydropyrimidine-2-thiones the mass spectra of a series of compounds of this group were studied. It is shown that equilibrium exists between the cyclic hydroxy form and the acyclic oxo form, which belongs to the oxoalkylthiourea class, in a series of 3-alkyl(aryl)-4,6,6-trimethyl derivatives in the gas phase. The mass spectra of these compounds contain intense peaks of [M-18]⁺ and [M-33]⁺ ions, which are formed as a result of the successive elimination of a water molecule and a methyl radical by the molecular ions. The fragmentation of 3-alkyl-4,5-dimethyl derivatives takes place from the open oxo form of the molecular ion with detachment of the terminal groups.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1273–1278, September, 1983.     

Synthesis and mass spectra of some 1-aroylamino-5-arylaminomethyl-1,2,3-triazoles

The title compounds 2 are prepared from the reaction of 1-(N, N-diaroyl)amino-5-bromomethyl-1,2,3-triazoles with aromatic amines. The fragmentation pattern upon electron impact at 70 eV of compounds 2 is studied. The molecular ion peak is present in all the spectra examined. Besides the [M-28]⁺⁺, there is also a more abundant [M-29]⁺ peak, corresponding to a N₂H loss of the molecular ion. The ion Ar²NH = CH₂ is the base or the most prominent peak.     

Mass Spectra of Furfuryl Aldoximes and Ketoximes

The mass spectra of 8 furfuryl aldoximes and ketoximes were studied under EI and CI conditions. Complicated fragmentation patterns were obtained in EI conditions, including formation of a furfuryl cation radical, furfuryl cation, and [M-17]⁺. The relatively simple patterns of cleavage resulted in few major ion peaks contributed from the adducts, protonation products, and dehydration products under CH₄-CI and NH₃-CI conditions. Comparison with the spectra of their isomeric amides indicated no evidence that the isomerization took place from oximes before fragmentation in both ionization methods.     

Mass-spectrometric investigation of isatins

It is shown that in the mass spectra of N-alkylisatins with a normal C₁-C₁₀ chain the intensity of the [M-CO]⁺- and [M-(2CO)]⁺. peaks characteristic for isatin and N-methylisatin decreases as the alkyl radical is lengthened, whereas the intensity of the peak formed as a result of successive loss by the molecular ion of a CO group and a portion of the radical as a result of cleavage of the bond at the α-carbon atom increases. Fragments due to α,β,γ... cleavages, both without migration and with migration of the hydrogen atoms, appear in the spectra of N-alkylisatins commencing with chains containing more than two C atoms.     

Mass-spectrometric behavior of isomeric nitro- and nitroaminoindolizines and indoles

Peaks of [M — NO]⁺ and [M — NO₂]⁺ ions are characteristic for the mass spectra of nitroindolizines, whereas peaks of ions of the indole type, viz., [M — HCN]⁺ and [M- H,- HCN]⁺ (for alkylindoles), are not characteristic. In the mass spectra of nitroindoles the latter ions give more intense peaks, while the loss of a nitro group or its rearrangement is a considerably less significant process. When a dialkylamino group is introduced in the nitroindolizine molecule, the primary processes in the fragmentation of such compounds are due to fragmentation of the alkylamino group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 765–768, June, 1982.     

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.     

C-C and C-H bond activation in the fragmentation of the [M + Ni]+ adducts of aliphatic amino acids

The major metal-containing species formed upon fast atom bombardment of amino acid/Ni⁺² mixtures is the [M + Ni]⁺ adduct, involving reduction of the Ni⁺² to the +1 oxidation state. By contrast, electrospray ionization of amino acid/Ni⁺² mixtures produces predominantly [Ni(M ? H)M]⁺; this species, on collisional activation, produces predominantly [M + Ni]⁺ by elimination of [M - H], presumably a carboxylate radical. The unimolecular fragmentation reactions occurring on the metastable ion time scale for the [M + Ni]⁺ adducts of a variety of α-amino acids have been recorded. The adducts with phenylalanine, α-aminoisobutyric acid and α-aminobutyric acid fragment by elimination of H₂O, H₂O + CO and, to a minor extent, by elimination of CO₂. These reactions are similar to those observed for the [M + Cu]⁺ adducts of α-amino acids. A reaction distinctive for the [M + Ni]⁺ adducts involves formation of the immonium ion RCH=NH ₂ ⁺ . By contrast, the [M + Ni]⁺ adducts with leucine, isoleucine, and norleucine show extensive metastable ion fragmentation by elimination of H₂, CH₄, C₂H₄, C₃H₆, and C₄H₈, with the relative importance of the different fragmentation channels depending on the configuration of the C₄H₉ side chain. These results are interpreted in terms of C-C and C-H bond activation of the C₄H₉ side chain by the Ni⁺. The adducts with valine and norvaline fragment in a fashion similar to the adduct with phenylalanine, except that minor elimination of C₃H₆ is observed.     

High resolution mass spectrometry—V: Cyclic esters of aliphatic α-hydroxy acids

The main fragmentation sequences of glycollide and its homologues are initiated by fission of a CO? O bond, leading to the formation of fragment ions of low, m/e, such as [R¹CO]⁺ and [CR¹R²CCO]⁺. When a hydrogen atom is present on a ring carbon atom, 1,3 hydrogen migration occurs to produce [CHR²OH]⁺. In case where a ring carbon atom carries an alkylchain ? C₂H₅, a McLafferty rearrangement occurs with the adjacent carbonyl group. When both ring carbon atoms are dimethyl substituted, a 1,4 hydrogen migration must be invoked to account for the observed fragmentation sequence.     

Mass spectrometry of stable free radicals—II: pyrrolidine nitroxides

3-Substituted-2,2,5,5-tetramethylpyrrolidine nitroxides are stable free radicals used extensively in the synthesis of ‘spin labels’. The high resolution mass spectra of these nitroxides substituted with ? CH₂OH, ? OH, ? NH₂ and ?o have been recorded on magnetic tape and the elemental compositions of the ions calculated by computer. Ionisation by electron bombardment(70eV), gives rise to an even-electron molecular ion species. [M+1]⁺. ions are observed in the spectra of all compounds examined, except in the case of the 3-carbonyl compound, 2,2,5,5-tetramethylpyrrolid-3-one-1-oxyl. Loss of a methyl radical from these ions leads to the appearance of ions at [M -14]⁺. The predominant fragmentation for those compounds in which the substituents can supply electrons to the ring, is the sequential elimination of isobutene, nitric oxide and a hydrogen radical. In the case of the 3-hydroxy compound, these ions account for 23 percent of the total ion current. 2,2,5,5-Tetramethylpyrrolid-3-one-1-oxyl, which bears an electron-withdrawing substituent gives rise to a fragmentation pattern somewhat different from those of the other compounds. The main features are the absence of a peak at [M + 1]⁺˙ and the general phenomenon of fewer peaks but with higher intensities.     

Mobile Proton Triggered Radical Fragmentation of Nitroarginine Containing Peptides

Protonated nitroarginine, [R^NO2 + H]⁺, which contains the nitroguanidine ‘explosophore,’ undergoes homolytic N – N nitro-imine bond cleavage to expel NO₂ ^? and form a radical cation of arginine in high yield (100 % relative abundance) upon low-energy collision-induced dissociation (CID). Other ionization states of nitroarginine, including [R^NO2 - H]^–, and a fixed-charge derivative of nitroarginine do not expel NO₂ ^? (<1 %), but instead dissociate via heterolytic bond cleavage with abundant losses of small molecules (N₂O and H₂N₂O₂) from the nitroguanidine group. The effects of proton mobility on the CID reactions of nitroarginine containing peptides was investigated for peptide derivatives of leucine enkephalin, including XYGGFLR^NO2, X = D, G, K, and R, by examining the different protonation states: [M – H]^–; [M + H]⁺; and [M + 2H]²⁺. For [M + H]⁺ containing the less basic N-terminal residues (X = D, G) and all [M + 2H]²⁺, mobile proton fragmentation reactions that result in peptide sequence ions dominate. In contrast, for peptides containing the basic N-terminal residues (R and K), the CID spectra of both the [M – H]^– and [M + H]⁺ are dominated by the losses of small even-electron neutrals from the nitroarginine side-chain. The fraction of nitroguanidine directed fragmentation of the nitroarginine side chain that results in bond homolysis to form [XYGGFLR]^+? by expulsion of NO₂ ^? increases by more than 10 times as the protonation state changes from [M – H]^– (<10 %) to [M + 2H]²⁺ (ca. 90 %) and by about four times as the acidity of the [M + H]⁺ N-terminal residue increases from R (19.0 %) to D (76.5 %). These results indicate that protonated peptides containing nitroarginine can undergo non-canonical mobile proton triggered radical fragmentation.

Mass Spectra of New Heterocycles. XVII. Main Fragmentation Routes of Molecular Ions of 4-Alkoxy-5-amino-3-methylthiophene-2-carbonitriles under Electron and Chemical Ionization

For the first time decomposition was investigated of 4-alkoxy-5-amino-3-methylthiophene-2-carbonitriles under the conditions of electronic (70 eV) and chemical (reagent gas methane) ionization. At the electronic ionization the compounds under study [except for 4-(1-ethoxyethoxy) and 4-(ferrocenylmethoxy) derivatives] form stable molecular ions that decompose mainly by the cleavage of an alkyl radical from the alkoxy-substituent. Further fragmentation of the arising ion [M–Alk]⁺ depends on the substituent nature in the amino group. In the mass spectrum of 4-(ferrocenylmethoxy)-substituted thiophene peaks of the ion [FcCH₂]⁺ and its fragmentation products prevail. In the mass spectra of chemical ionization predominant peaks belong to ions M^+·, [M + H]⁺ and [M + C₂H₅]⁺, and fragment ions are absent.     

One and two hydrogen atom migrations in the retro-diels-alder fragmentation of norbornene and bicyclo [2.2.2] octene derivatives under electron impact

Norbornene derivatives with one or two carbonyl-containing substituents at positions 5 and 6 (anhydrides, esters, amides, cyclic ketones) undergo an electron impact induced rerro-Diels-Alder fragmentation accompanied by the migration of one hydrogen atom (RDA + H) giving rise to the [dienophile + H]⁺ ions. Bicyclo[2.2.2]octene derivatives substituted at C(5) and C(6) by a ring with two carbonyl groups (anhydrides, imides, diketones) undergo an RDA fragmentation accompanied by the transfer of two hydrogen atoms (RDA + 2H). Bicyclo[2.2.2]octene 5,6-diesters undergo both the RDA + H and RDA + 2H fragmentations, and the relative abundance of the resulting [dienophile + H]⁺ and [dienophile + 2H]⁺˙ ions is strongly affected by configuration.     

Mobile protons versus mobile radicals: Gas-phase unimolecular chemistry of radical cations of cysteine-containing peptides

A combination of electrospray ionization (ESI), multistage, and high-resolution mass spectrometry experiments are used to examine the gas-phase fragmentation reactions of radical cations of cysteine containing di- and tripeptides. Two different chemical methods were used to form initial populations of radical cations in which the radical sites were located at different positions: (1) sulfur-centered cysteinyl radicals via bond homolysis of protonated S-nitrosocysteine containing peptides; and (2) α-carbon backbone-centered radicals via Siu’s sequence of reactions (J. Am. Chem. Soc. 2008, 130, 7862). Comparison of the fragmentation reactions of these regiospecifically generated radicals suggests that hydrogen atom transfer (HAT) between the α C-H of adjacent residues and the cysteinyl radical can occur. In addition, using accurate mass measurements, deuterium labeling, and comparison with an authentic sample, a novel loss of part of the N-terminal cysteine residue was shown to give rise to the protonated, truncated N-formyl peptide (an even-electron x_n ion). DFT calculations were performed on the radical cation [GCG]^.+ to examine: the relative stabilities of isomers with different radical and protonation sites; the barriers associated with radical migration between four possible radical sites, [G.CG]⁺, [GC.G]⁺, [GCG.]⁺, and [GC(S.)G]⁺; and for dissociation from these sites to yield b₂-type ions.     

Mass spectroscopic study of 2,5-dimethyl-4-benzoyl- and 2,5-dimethyl-4-benzylpyridine derivatives

The dissociative ionization of sixteen 4-benzoyl- and 4-benzylpyridine derivatives and their deuteroanalogs has been studied. An ortho effect, due to the benzoyl and benzyl radicals in the methyl group in the 5-position of the pyridine ring, has been detected. It has also been established that fragmentation of 4-benzoylpyridines substituted with a nitro group in the benzene ring leads to [M-OH]⁺ ions, due to the ortho effect, whereas fragmentation of 4-benzylpyridines leads to [M-C₆H₅R]⁺ ions. The probability of a given process depends on the position and nature of any substituent in the benzene ring; this makes it possible to identify different isomers in a given series of compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 810–816, June, 1987.     

Characterisation of selected hypnotic drugs and their metabolites using electrospray ionisation with ion trap mass spectrometry and with quadrupole time-of-flight mass spectrometry and their determination by liquid chromatography-electrospray ionisation-ion trap mass spectrometry

The electrospray ionisation-ion trap mass spectrometry (ESI-MSⁿ) of selected hypnotic drugs, i.e. zopiclone, zolpidem, flunitrazepam and their metabolites have been investigated. Sequential product ion fragmentation experiments (MSⁿ) have been performed in order to elucidate the degradation pathways for the [M+H]⁺ ions and their predominant fragment ions. These MSⁿ experiments show certain characteristic fragmentations in that functional groups are generally cleaved from the ring systems as neutral molecules such as H₂O, CO, CO₂, NO₂, amines and HF. When an aromatic entity is present in a drug molecule together with a nitrogen-containing saturated ring structure as with zopiclone and its N-desmethyl metabolite fragmentation initially occurs at the latter ring with the former being resistant to fragmentation. The structures of fragment ions proposed for ESI-MSⁿ can be supported by electrospray ionisation-quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS).These molecules can be identified and determined in mixtures at low ng/ml concentrations by the application of liquid chromatography (LC)-ESI-MSⁿ which can be used for their analysis in saliva samples.This paper includes a tabulation of mass losses/signals at low m/z values for these hypnotic drugs and many others in recent publications which will be of value in the characterisation of drug metabolites of unknown structure and also natural product pharmaceuticals isolated from plants, etc.