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.     

Nitrogen incorporation in saturated aliphatic C6–C8 hydrocarbons and ethanol in low‐pressure nitrogen plasma generated by a hollow cathode discharge ion source

Ion/molecule reactions of saturated hydrocarbons (n‐hexane, cyclohexane, n‐heptane, n‐octane and isooctane) in 28‐Torr N₂ plasma generated by a hollow cathode discharge ion source were investigated using an Orbitrap mass spectrometer. It was found that the ions with [M+14]⁺ were observed as the major ions (M: sample molecule). The exact mass analysis revealed that the ions are nitrogenated molecules, [M+N]⁺ formed by the reactions of N₃⁺ with M. The reaction, N₃⁺ + M → [M+N]⁺ + N₂, were examined by the density functional theory calculations. It was found that N₃⁺ abstracts the H atom from hydrocarbon molecules leading to the formation of protonated imines in the forms of R′R″C?NH₂⁺ (i.e. C–H bond nitrogenation). This result is in accord with the fact that elimination of NH₃ is the major channel for MS/MS of [M+N]⁺. That is, nitrogen is incorporated in the C–H bonds of saturated hydrocarbons. No nitrogenation was observed for benzene and acetone, which was ascribed to the formation of stable charge‐transfer complexes benzene????N₃⁺ and acetone????N₃⁺ revealed by density functional theory calculations. Copyright © 2016 John Wiley & Sons, Ltd.     

Anomalies in the molecular ion region in the electron impact mass spectra of α- and β-hydroxyesters

In the electron impact mass spectra of some alkyl α- and β-hydroxyesters (introduced using the gas chromatography/mass spectrometry (GC/MS) technique), the absence of the molecular ion M^+· and the presence of the [M + 1]⁺ ion instead is observed. This phenomenon is especially characteristic of C₃? C₆ glycolates and diethyl malate, and is due to chemical auto-ionization—ion-molecule reactions in the high concentration gradient at the top of the GC peak. The existence of the [M ? 2]^+·, [M ?1]⁺ and M^+· ions in the mass spectra of other β- and α-hydroxyesters is discussed.     

Mass spectrometry of hydroxyammoniocarboxylates: Lactonization of thermally rearranged molecules during field desorption

The field desorption mass spectral behavior of several hydroxyammoniocarboxylates was studied at both low and high emitter heating currents. The molecular weights of these thermally unstable compounds can be determined directly from the low emitter current (<10 mA) field desorption mass spectra, which are dominated by [xM+H]⁺ and [xM+H? CO₂]⁺ ions (1?x?4). At higher emitter currents (～20 mA), pyrolytic processes become important. These include intermolecular transfer of a single alkyl group yielding [M+alkyl]⁺ ions, intermolecular isomerization producing a hydroxyaminoester as the rearranged form of the molecule, and elimination of alcohol from the rearranged molecule, producing γ or δ lactones. The distribution of pyrolysis products does not depend significantly on the length of the carboxylate chain, but does appear to depend upon the chain length of the alkyl substituent on nitrogen. The spectra of molecules containing a long alkyl substituent (e.g. C₁₄H₂₉, C₂₂H₄₅) exhibit relatively high levels of [M+alkyl]⁺ ions, unlike the spectra of compounds which contain only methyl or ethyl substituents on the quaternary nitrogen. These latter compounds exhibit a relatively greater tendency toward lactone formation.     

Ion-molecule reactions of oxygenated chemical ionization reagents with vincamine

The ion-molecule reactions of ions from acetone, dimethyl ether, 2-methoxyethanol, and vinyl methyl ether with vincamine were investigated. Reactions with dimethyl ether result in [M+13]⁺ and [M+45]⁺ products, reactions with 2-methoxyethanol produce [M+13]⁺ and [M+89]⁺ ions, and reactions with acetone or vinyl methyl ether ions generate predominantly [M+43]⁺ ions. Collision-activated dissociation and deuterium labeling experiments allowed speculation about the product structures and mechanisms of dissociation. The methylene substitution process was shown to occur at the hydroxyl oxygen and the phenyl ring of vincamine for dimethyl ether reactions, but the methylene substitution process was not favored at the hydroxyl oxygen for the 2-methoxyethanol reactions, instead favored at the 12 phenyl position. The reaction site is likely different for the 2-methoxyethanol ion due to its capability for secondary hydrogen-bonding interactions. For the [M+45]⁺ and [M+89]⁺ ions, evidence suggests that charge-remote fragmentation processes occur from these products. In general, the use of dimethyl ether ions or 2-methoxyethanol ions for ionmolecule reactions prove highly diagnostic for the characterization of vincamine; both molecular weight and structural information are obtained. Limits of detection for vincamine with dimethyl ether chemical ionization via this technique on a benchtop ion trap gas chromatography-tandem mass spectrometer are in the upper parts per trillion range.     

Repeller-Induced dissociation of alkyl alcohols in thermospray mass spectrometry

Six alkyl alcohols were studied using thermospray mass Spectrometry. Whereas the dominant ion in the spectrum up to a repeller potential of 120 V was [M + NH₄]⁺, above that potential [M + H]⁺ and fragment ions appeared. The fragments observed were largely due to hydrogen release from alkyl ions ([C_nH_2n+1]⁺ – H2 → [C_nH_2n-1]⁺) and loss of water or some other stable molecule from the same species. The results are compared with those from ionization of the same alcohols under electron impact and photoionization conditions and with results obtained for methanol under thermospray conditions.     

Unique thermospray mass spectrometry of 1,4-benzoquinone and analogs in ammonium acetate solutions

In general, ions corresponding to [M + H]⁺ and/or [M + NH₄]⁺ are observed in thermospray mass spectrometry (TSMS) when using ammonium acetate in the liquid carrier. For several quinones investigated, unique thermospray mass spectra were detected with a mass spectral peak corresponding to an [M + 16]⁺ ion being observed in aqueous ammonium acetate solutions. Investigation of l,4-benzoquinone (BQU) and structurally analogous quinones indicated that amine conjugate formation with BQU and similar quinones was the origin of the unique [M + 16]⁺ ion in TSMS. When methanol was added to the liquid carrier, ions corresponding to methoxy conjugation were detected. High-performance liquid chromatography followed by TSMS or electrochemical detection gave evidence that this amine and methoxy conjugate formation was occurring in the thermospray source area.     

Isobutane chemical ionization mass spectra of unsaturated alcohols

Analysis of the isobutane chemical ionization mass spectra of hexenols, cyclohexenols and various syn/anti pairs of bicyclic and tricyclic homoallylic alcohols shows that: (i) the spectra of the allylic alcohols are dominated by [M + H – H₂O]⁺ and [M + C₄H₉–H₂O]⁺ ions and contain traces of [M + H]⁺ ions; (ii) [M + H]⁺ ions are prominent in the spectra of acyclic and certain cyclic homoallylic alcohols; and (iii) [M + H]⁺ ions dominate the spectra of other acyclic unsaturated alcohols. The [M + H]⁺ ions may result from either: (a) protonation of the hydroxyl group, followed by a very rapid intramolecular proton transfer from the protonated hydroxyl group to the carbon–carbon double bond or internal solvation of the protonated hydroxyl group by the carbon–carbon double bond; and/or (b) direct protonation of the carbon–carbon double bond with significant internal solvation of the resulting carbocation by the hydroxyl group, which may lead to carbon–oxygen bond formation to give a protonated cyclic ether. The consequences of placing various geometric constraints on the possible intramolecular interactions between the hydroxyl group and the carbon–carbon double bond in unsaturated alcohols are explored.     

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]⁺.     

A mechanistic study of the H/D exchange reactions of protonated arginine and arginine-containing Di- and tripeptides

The gas-phase H/D exchange reactions of arginine (R) and arginine-containing di- and tri-peptide (gly-arg (GR), arg-gly (RG), gly-gly-arg (GGR), gly-arg-gly (GRG) and arg-gly-gly (RGG)) [M+H]⁺ ions with deuterated ammonia (ND₃) were investigated by using Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR), ion mobility-mass spectrometry (IM-MS), ab initio and density functional theory-based molecular orbital calculations and molecular modeling. Three exchanges are observed for arginine and arginine-containing tri-peptide [M+H]⁺ ions, whereas the di-peptide [M+H]⁺ ions undergo a single H/D exchange. In addition, C-terminal methylation blocks H/D exchange of arginine and the arginine-containing peptide [M+H]⁺ ions, and a single H/D exchange is observed for N-terminal acetylated arginine [M+H]⁺ ions. A general mechanism for H/D exchange involving a collision complex that is best described as a “solvated salt-bridge” structure is proposed.     

Effect of alkali metal cationization on the collision-induced decomposition of alkyl per-O-acetyl-2-deoxy-2-halo-α-O-mannopyranosides

The effect of alkali metal cationization on the collision-induced decomposition of alkyl per-O-acetyl-2-deoxy-2-bromo-and-iodo-α-O-mannopyranosides was studied. The bromo sugars gave fairly abundant MH⁺, whereas for the iodo sugars the MH⁺ ions were insignificant. However, both the bromo and the iodo derivatives gave abundant M + alkali metal ion complexes. In contrast to the behaviour of the MH⁺ ion, the [M + Li]⁺, [M + Na]⁺ and [M + K]⁺ ions of these compounds do not decompose by loss of the C(1) substituent. Elimination of AcOH is the preferred fragmentation pathway of [M + Cat]⁺. Elimination of HX occurs only after loss of AcOH and CH₂CO from MH⁺, whereas [M + Cat]⁺ directly loses HX. The elimination of HX is more pronounced from [M + Na]⁺ and [M + K]⁺ than from [M + Li]⁺. Loss of AcOLi is an additional fragmentation route observed in the case of the decomposition of [M + Li]⁺ ion.     

Selective ion-molecule reactions of lactams with dimethyl ether ions

The ion-molecule reactions of dimethyl ether ions CH₃OCH₃ ⁺ and (CH₃OCH₃)H⁺, and four- to seven-membered ring lactams with methyl substituents in various positions were characterized by using a quadrupole ion trap mass spectrometer and a triple-quadrupole mass spectrometer. In both instruments, the lactams were protonated by dimethyl ether ions and formed various combinations of [M + 13] ⁺, [M + 15] ⁺, and [M + 45] ⁺ adduct ions, as well as unusual [M + 3] ⁺ and [M + 16] ⁺ adduct ions. An additional [M + 47] ⁺ adduct ion was formed in the conventional chemical ionization source of the triple-quadrupole mass spectrometer. The product ions were isolated and collisionally activated in the quadrupole ion trap to understand formation pathways, structures, and characteristic dissociation pathways. Sequential activation experiments were performed to elucidate fragment ion structures and stepwise dissociation sequences. Protonated lactams dissociate by loss of water, ammonia, or methylamine; ammonia and carbon monoxide; and water and ammonia or methylamine. The [M + 16] ⁺ products, which are identified as protonated lactone structures, are only formed by those lactams that do not have an N-methyl substituent. The ion-molecule reactions of dimethyl ether ions with lactams were compared with those of analogous amides and lactones.     

Mass spectrometric behaviour of 1-imino-substituted pyrazolo[1,2-a]-[1,2,4]triazoles under electron and chemical ionization

The spectra of five pharmacologically interesting substituted pyrazolo[1,2-a][1,2,4]triazole hydroiodides were measured under electron and chemical ionization. In the electron ionization spectra, in addition to the intense molecular ion peak of the free base (M⁺*), there was also a relatively intense molecular ion peak of the hydroiodide form, which is unusual since the hydroiodides are rarely so stable. The phenylimino and phenylamino substituents of the triazole ring affected the fragmentation behaviour of the compounds very much. The chemical ionization reagent gases used in this work were methane, isobutane, deuterated ammonia and acetone. In all the cases practically only [M+H]⁺ ions were observed, the only exception being acetone which also gave rise to intense [M+C₂H₃O]⁺ and [M⁺C₃H₇O]⁺ adduct ions. None of the reagent gases used was able to cause any fragmentation.     

In-beam electron impact mass spectrometry of aliphatic alcohols

The characteristics of the in-beam electron impact mass spectra of six isomers of undecanol as well as several 1-alkanols have been examined. In addition to the characteristic ions observed in the conventional electron impact spectra, the [2M+1]⁺, [2M+1-H₂O]⁺, [2M+1-2H₂O]⁺, [2M-R or R′]⁺, [2M-H₂O? R or R′]⁺, [2M? 2H₂O? R or R′]⁺ and [M+1? H₂O]⁺ peaks are common in the in-beam electron impact mass spectra of the undecanol isomers of structure RCH(OH)R′. Deuterium labelling experiments have shown that the extra proton in the protonated dimer ions, [2M+1]⁺, originates from the hydroxy group. The processes which produce the important peaks in the high m/e regions are discussed.     

Mass spectrometric monitoring of oxidation of aliphatic C6–C8 hydrocarbons and ethanol in low pressure oxygen and air plasmas

Experimental and theoretical studies on the oxidation of saturated hydrocarbons (n‐hexane, cyclohexane, n‐heptane, n‐octane and isooctane) and ethanol in 28 Torr O₂ or air plasma generated by a hollow cathode discharge ion source were made. Ions corresponding to [M + 15]⁺ and [M + 13]⁺ in addition to [M ? H]⁺ and [M ? 3H]⁺ were detected as major ions where M is the sample molecule. The ions [M + 15]⁺ and [M + 13]⁺ were assigned as oxidation products, [M ? H + O]⁺ and [M ? 3H + O]⁺, respectively. By the tandem mass spectrometry analysis of [M ? H + O]⁺ and [M ? 3H + O]⁺, H₂O, olefins (and/or cycloalkanes) and oxygen‐containing compounds were eliminated from these ions. Ozone as one of the terminal products in the O₂ plasma was postulated as the oxidizing reagent. As an example, the reactions of C₆H₁₄^+? with O₂ and of C₆H₁₃⁺ (CH₃CH₂CH⁺CH₂CH₂CH₃) with ozone were examined by density functional theory calculations. Nucleophilic interaction of ozone with C₆H₁₃⁺ leads to the formation of protonated ketone, CH₃CH₂C(=OH⁺)CH₂CH₂CH₃. In air plasma, [M ? H + O]⁺ became predominant over carbocations, [M ? H]⁺ and [M ? 3H]⁺. For ethanol, the protonated acetic acid CH₃C(OH)₂⁺ (m/z 61.03) was formed as the oxidation product. The peaks at m/z 75.04 and 75.08 are assigned as protonated ethyl formate and protonated diethyl ether, respectively, and that at m/z 89.06 as protonated ethyl acetate. Copyright © 2016 John Wiley & Sons, Ltd.     

Reduction of cationic free-base <Emphasis Type="Italic">meso</Emphasis>-tris-<Emphasis Type="Italic">N</Emphasis>-methylpyridinium-4-yl porphyrins in positive mode electrospray ionization mass spectrometry

Reductions involving more than one electron with formation of the M⁺ and [M+2H]⁺ ions were observed for electrosprayed meso-tris(N-methylpyridinium-4-yl)porphyrin iodides, MI₃. These reductions were studied by using different solvents and flow rates. Formation of the [M+2H]⁺ ions occurred only for protic solvents and to a larger extent at lower flow rates. The type of the fourth substituent does not seem to affect the reduction processes. Formation of the two reduced species, M⁺ and [M+2H]⁺ ions, may occur through the participation of counter ion/solvent clusters. Reduction of multiply charged, non-metallated species with formation of [M+nH]⁺ ions (n>1) was not observed before in positive mode electrospray mass spectrometry.     

Direct analysis of Salvia divinorum leaves for salvinorin A by thin layer chromatography and desorption electrospray ionization multi‐stage tandem mass spectrometry

Salvia divinorum is widely cultivated in the US, Mexico, Central and South America and Europe and is consumed for its ability to produce hallucinogenic effects similar to those of other scheduled hallucinogenic drugs, such as LSD. Salvinorin A (SA), a kappa opiod receptor agonist and psychoactive constituent, is found primarily in the leaves and to a lesser extent in the stems of the plant. Herein, the analysis of intact S. divinorum leaves for SA and of acetone extracts separated using thin layer chromatography (TLC) is demonstrated using desorption electrospray ionization (DESI) mass spectrometry. The detection of SA using DESI in the positive ion mode is characterized by several ions associated with the compound – [M+H]⁺, [M+NH₄]⁺, [M+Na]⁺, [2M+NH₄]⁺, and [2M+Na]⁺. Confirmation of the identity of these ions is provided through exact mass measurements using a time‐of‐flight (ToF) mass spectrometer. The presence of SA in the leaves was confirmed by multi‐stage tandem mass spectrometry (MSⁿ) of the [M+H]⁺ ion using a linear ion trap mass spectrometer. Direct analysis of the leaves revealed several species of salvinorin in addition to SA as confirmed by MSⁿ, including salvinorin B, C, D/E, and divinatorin B. Further, the results from DESI imaging of a TLC separation of a commercial leaf extract and an acetone extract of S. divinorum leaves were in concordance with the TLC/DESI‐MS results of an authentic salvinorin A standard. The present study provides an example of both the direct analysis of intact plant materials for screening illicit substances and the coupling of TLC and DESI‐MS as a simple method for the examination of natural products. Copyright © 2010 John Wiley & Sons, Ltd.     

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.     

Acetone chemical ionization studies: Olefins

Acyclic, cyclic and bicyclic olefins have been found to undergo acetylation in the gas phase under acetone chemical ionization, giving rise to diagnostic ions. Terminal olefins show enhanced loss of water from the [M + 43]⁺ adduct. The [M + 43]⁺ ion of Δ³? Δ⁴? and Δ⁵-olefins give characteristic collision-induced dissociation spectra.     

Ion–molecule reactions in the gas phase. XVIII.—nucleophilic substitution of diastereomeric norborneols,norbornyl acetates and benzoates under ammonia chemical ionization

The comparative behaviour of the endo- and exo-norborneols and diastereomeric derivatives (acetates and benzoates) towards the NH₃/NH₄⁺ system was investigated. It appears that the proton affinity (PA) of the substrate relative to Pa(NH₃) strongly influences competition between the protonation and nucleophilic substitution processes yielding the MH⁺ and [M + NH₄ ? H₂O]⁺ ions, respectively. Tandem mass spectrometry was used to compare collision-activated dissociation spectra of [M + NH₄ ? H₂O]⁺ with those of analogous endo- and exo-norbornylamines protonated in the source. This demonstrates that an S_Nimechanism occurs specifically for the isomeric norborneols; in contrast, for acetates and benzoates, stereospecific S_Ni and S_N2 pathways take place for exo and endo derivatives, respectively. This particular behaviour is explained by considering the steric effect induced by the endo-H at C(6). In addition, the competitive decompositions of [M + NH₄ – H₂O]⁺ into NH₄⁺ and [C₇H₁₁]⁺ daughter ions are consistent with the formation of a proton-bound complex intermediate. The observed stereochemical effects for these dauther ions are rationalized by means of arguments based on the estimated heats of formation of the transition states, which is lower for the exo-norbonyl protonated amine, consistent with anchimeric assistance, rather than a stepwise pathway which is proposed for the endoisomer.