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.     

Ion–molecule reactions and dissociation of glycols in a quadrupole ion trap mass spectrometer: Evidence of intramolecular interactions

Polyethylene glycols react with CH₃OCH₂⁺ ions from dimethyl ether to form [M + 13]⁺ products. The [M + 13]⁺ ions are stabilized by intramolecular interactions involving the internal ether oxygen atoms and the terminal methylene group. Collisionally activated dissociation (CAD), including MSⁿ and deuterium labeling experiments show that fragmentation reactions involving intramolecular cyclization are predominant. Scrambling of hydrogen and deuterium atoms in the ion-molecule reaction products is not indicated. The CAD spectra of the [M + 13]⁺ ions provide unambiguous assignment of the glycol size.     

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.     

Effects of functional group interactions on the gas-phase methylation and dissociation of acids and esters

Functional group interactions have been observed to affect gas-phase ion-molecule chemistry in a quadrupole ion trap mass spectrometer. Gas-phase methylation and collisionactivated dissociation reactions of a series of related acids and esters allows an evaluation of the structural factors that influence reactivity and functional group interactions of these compounds. Examination of the [M+H]⁺ or [M+15]⁺ product ions by collision-activated dissociation has provided insight into the conformations from which diacids and diesters undergo electrophilic addition. Collision-activated dissociation has provided not only more detailed information on the structures of the ions, but also the data necessary for confident mechanistic interpretation. Labeling studies were done to probe fragmentation pathways. Upon activation of the [M+CD₃]⁺ products of dimethyl maleate and dimethyl succinate, formed from reaction of the neutrals with CD₃OCD ₂ ⁺ ions, a rapid interfunctional group methyl transfer causes scrambling of the methyls prior to elimination of dimethyl ether or methanol. The [M+15]⁺ ions of dimethyl maleate are believed to lose dimethyl ether through a rate-determining 1,6-methyl transfer, whereas the [M+15]⁺ ions of dimethyl succinate eliminate methanol through a rate-determining 1,5-proton transfer.     

An investigation of site-selective gas-phase reactions of amino alcohols with dimethyl ether ions

The reactions of dimethyl ether ions with neutral amino alcohols were examined in both a quadrupole ion trap mass spectrometer and a triple quadrupole mass spectrometer. These ion-molecule reactions produced two types of ions: the protonated species [M+l]⁺ and a more complex product at [M+13]⁺. The abundance of the [M+13]⁺ ions relative to that of the [M+1]⁺ ions decreases with increasing formal interfunctional distance. Multistage collision-activated dissociation techniques were used to characterize the [M+13]⁺ product ions, their reactivities, and the mechanisms for their formation and dissociation. In addition, molecular semiempirical calculation methods were used to probe the thermochemistry of these reactions. Reaction at the amino alcohol nitrogen site is favored, and the resulting [M+13]⁺ addition products may cyclize for additional stabilization. Comparisons were made among the behavior of related compounds, such as alcohols, diols, amines, and diamines. The alcohols reacted only to form the protonated species, but the diols, amines, and diamines all formed significant amounts of [M+13]⁺ ions or related dissociation products.     

Examination of Ortho effects in the collisionally activated dissociation of closed-shell aromatic ions

The collisionally activated dissociation of a variety of isomeric disubstituted aromatic ions formed by ion–molecule reactions were examined in order to characterize ortho effects in closed-shell systems. Closed-shell ions of methoxyacetophenone, hydroxyacetophenone, methoxyphenol, anisaldehyde and hydroxybenzaldehyde were formed by proton transfer, methyl addition or methyne addition by using dimethyl ether or ethylene oxide as chemical ionization reagents, and then the structures of these adducts were studied by deuterium-labelling methods and by collisionally activated dissociation techniques in a triple quadrupole mass spectrometer or a quadrupole ion trap. Typically, the meta and para isomers have qualitatively similar dissociation spectra which reflect the types of dissociation reactions observed for the corresponding monosubstituted aromatic ions. The predominant dissociation pathways of the [M + H]⁺ and [M + 15]⁺ ions are directed by the electron-withdrawing substituents, whereas the major dissociation pathways of the [M + 13]⁺ ions are related to the electron-releasing substituent. In contrast, the dissociation routes of the corresponding ortho isomers are dramatically different. This is attributed to the opportunity for functional group interactions of the ortho isomers which facilitate alternative pathways.     

Methylene substitution reactions in a quadrupole ion trap selectivity of ethylene,ethylene oxide,and dimethyl ether reactive ions

To elucidate the selectivity of methylene substitution reactions of monosubstituted and disubstituted oxyaromatic compounds in a low pressure quadrupole ion trap environment, the relative abundances of covalently bound and loosely bound adducts formed by ion/molecule reactions with ethylene (ET), ethylene oxide (ETOX), and dimethyl ether (DME) were compared. Adduct ions of all three reagent gases were formed in both a conventional ion source and a quadrupole ion trap and characterized by collisionally activated dissociation. For DME and ET, the covalently bound adducts formed at (M + 45)⁺ and (M + 41)⁺, respectively, are direct precursors to the methylene substitution product ions at (M + 13)⁺. ETOX and ET do not demonstrate the same functional group selectivity for methylene substitution as previously observed for DME. This is attributed to differences in reaction exothermicities and competing reactions.     

Gas-phase complexation of polyethers with halide ions

Gas-phase complexes of halide anions with a variety of crown ethers and acyclic analogs are formed by ion-molecule reactions in the chemical ionization source of a triple-quadrupole mass spectrometer. The ether complexes of iodide, bromide, and chloride dissociate on collisional activation by cleavage of the halide-ether electrostatic hydrogen bonds, resulting in the formation of bare halide anions. By contrast, the fluoride complexes dissociate by loss of HF, which may occur in conjunction or sequentially with losses of ethylene oxide units. This dissociation behavior is similar to that observed for collisionally activated dissociation of [M ? H]^? ions of the crown ethers and suggests that the fluoride ion is capable of promoting an intramolecular proton abstraction within the [M+F]^? complex. This type of dissociation chemistry is only observed for the fluoride ion complexes, and the fluoride ion is the most basic of all the halides. The kinetic method was used to establish orders of relative halide binding strengths, and the trends for the chloride and bromide affinities were 12-crown-4 < triethylene glycol dimethyl ether < 15-crown-5 < tetraethylene glycol dimethyl ether < 18-crown-6 < 21-crown-7 < tetraethylene glycol < pentaethylene glycol < 1,4,7,10,13-pentathiacyclopentadecane.     

Tandem mass spectrometry of lithium-attachment ions from polyglycols

A detailed study has been carried out of the fast atom bombardment tandem mass spectrometry (MS/MS) behavior of lithium-attachment ions from three glycol polymers: linear poly(ethylene glycol), linear poly(propylene glycol), and an ethoxylated fatty alcohol. Collisional activation was carried out in the “collision octapole” of a BEoQ hybrid mass spectrometer at a translational energy of 50 eV, with collision gas air. It was found that [M + Li]⁺ ions provide a number of advantages as precursors for practical MS/MS analysis as compared to the use of [M + H]⁺ or [M + Na]⁺ ions. First, [M + Li]⁺ ions are much more intense than the corresponding [M + H]⁺ ions. Second, [M + Li]⁺ ions dissociate to lithiated organic fragments with reasonable efficiency, which is not the case with [M + Na]⁺ precursors. Third, product ions are generally formed over the entire mass range for low molecular weight polyglycols. The most intense product ions are lithiated, linear polyglycol oligomers. These ions are formed via internal hydrogen transfer reactions which are facilitated by lithium (charge-induced). Two series of less intense product ions are formed via charge-remote fragmentations involving l,4-hydrogen elimination. A fourth product ion series consists of lithiated radical cations; these form via homolytic bond cleavages near chain ends. Overall, MS/MS analysis of [M + Li]⁺ polyglycol ions proved to be quite useful for chemical structure elucidation.     

Ion formation in fast atom bombardment mass spectrometry: a divided probe investigation of gas-phase reactions

Some ion-formation processes during fast atom bombardment (FAB) are discussed, especially the possibility of reactions in the gas phase. Divided (two halves) FAB probe tips were used for introducing two different samples into the source at the same time. Our results showed [M + A]⁺ ions (where M = crown ethers and A = alkali metal ions), can be produced, at least in part, in the gas phase when crown ethers and sources of alkali metal ion are placed on two halves of the FAB probe tip. The extent of this ion formation depends on the volatility of the crown ether and on steric factors. Cluster ions such as (M + LiCl)Li⁺, (2M + LiCl)Li⁺, [2M + K]⁺ and [2M + Na]⁺ are also observed to form in the gas phase. Unimolecular decompositions contribute to some ions detected in FAB. When the alkali ion salt and the crown ether are mixed together the probability of [M + A]⁺ ion formation increases significantly, regardless of the volatility of the crown ether.     

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.     

Effects of functional group interactions on the bimolecular and dissociation reactions of diols

The influence of functional group interactions on the bimolecular and dissociation reactions of diols were examined in a quadrupole ion trap mass spectrometer. Reactions of dimethyl ether ions with diols resulted in formation of (M + H)⁺ ions and (M + 13)⁺ ions (by net methyne addition). The product distribution depended on the relative separation of the hydroxyl groups within each diol, with the more proximate diols producing the greatest abundance of (M + 13)⁺ ions compared to (M + H)⁺ ions. The enhancement of the formation of (M + 13)⁺ ions is attributed to the capability for electrostatic interactions between the hydroxyl groups and the electropositive methylene group of the methoxymethylene reagent ion. The enhancement is most significant for diols that can adopt five- or to a lesser extent six-membered ring transition states (i.e, any 1,2 or 1,3 diol). Collision-activated dissociation (CAD) techniques, including both sequential activation experiments (MS ⁿ ) and comparison of CAD spectra for model compounds, suggest that the (M + 13)⁺ ions are protonated cyclic diethers.     

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.     

Ion-molecule reactions in the gas phase. part XXII. Reactivity of the cis- and trans-indanediols with dimethyl ether ions

Specific reactivity of cis- and trans-indanediols has been investigated under dimethyl ether (DME) chemical ionization conditions. Several unusual species, such as [M + 29]⁺ and [M + 27]⁺ ions, are produced in high yield. From DME pressure variations and tandem mass spectrometry experiments (low-energy collisions with Ar and NH₃) including some labeled compounds, it appears that [M + 29]⁺ ions are generated by nucleophilic substitution according to a S_Ni pathway from the proton bound[M + DMEH]⁺ adduct ion. On the other hand, [M + 27]⁺ ions are produced from the covalent [M + DME ? H]⁺ adduct ions via a stepwise process inducing a water loss. This latter dehydration occurs from the adducts prepared by [DME ? H]⁺ attachment to the homobenzylic hydroxy site, which allows internal proton transfer from the charged position to the benzylic hydroxy group, promotingthe loss of water. In addition, trans indanediol labeled with ¹⁸O has been used to obtain evidence for the regioselectivity of both water-loss mechanisms from the benzylic site.     

Collision-induced decompositions of metal-cationized methyl-6-deoxy-6-bromo-α-D-glucopyranoside derivatives

Collision-induced decompositions (CIDs) of the [M + H]⁺, [M + Li]⁺, [M + Na]⁺, [M + K]⁺ and [M + Ag]⁺ ions of some methyl-6-deoxy-6-bromo-α-D-glucopyranoside derivatives are discussed. Elimination of MeOH resulting in the glycosidyl cation is the predominant reaction of the [M + H]⁺ ion. This process is completely suppressed during CID of the metal-cationized species, which, surprisingly, show elimination of the added metal in the form of RCOO-metal and metal bromide in the case of the ester derivatives. These reactions appear to be assisted by neighbouring group participation. Because of the proximity of the C(3)-oxygen with C(6), the benzyl ether derivative is characterized by the loss of PhCH₂Br from the [M + metal]⁺ ion.     

Electrospray mass analysis of chemical oxidation of 1,2-diarylcyclopropanes by Cu(II) salt

Electrospray ionization mass spectrometry was used to study chemical electron-transfer reactions of 1,2-diarylcyclopropanes by Cu(II) salt in acetonitrile. The ion [M ? H]⁺ with a hydrogen atom loss and the solvent adduct ions, [M+42]⁺, etc., were detected as the initial reaction products, where [M+42]⁺ represents the ion whose mass is 42 u greater than the parent molecule M. From the study of deuterated derivatives, the hydrogen abstraction was revealed to occur at the 3 position of the cyclopropanes, and the mechanism of the hydrogen abstraction reaction and of the solvent addition were discussed.     

Use of a hand-portable gas chromatograph-toroidal ion trap mass spectrometer for self-chemical ionization identification of degradation products related to O-ethyl S-(2-diisopropylaminoethyl) methyl phosphonothiolate (VX)

The chemical warfare agent O-ethyl S-(2-diisopropylaminoethyl) methyl phosphonothiolate (VX) and many related degradation products produce poorly diagnostic electron ionization (EI) mass spectra by transmission quadrupole mass spectrometry. Thus, chemical ionization (CI) is often used for these analytes. In this work, pseudomolecular ([M+H]⁺) ion formation from self-chemical ionization (self-CI) was examined for four VX degradation products containing the diisopropylamine functional group. A person-portable toroidal ion trap mass spectrometer with a gas chromatographic inlet was used with EI, and both fixed-duration and feedback-controlled ionization time. With feedback-controlled ionization, ion cooling (reaction) times and ion formation target values were varied. Evidence for protonation of analytes was observed under all conditions, except for the largest analyte, bis(diisopropylaminoethyl)disulfide which yielded [M+H]⁺ ions only with increased fixed ionization or ion cooling times. Analysis of triethylamine-d₁₅ provided evidence that [M+H]⁺ production was likely due to self-CI. Analysis of a degraded VX sample where lengthened ion storage and feedback-controlled ionization time were used resulted in detection of [M+H]⁺ ions for VX and several relevant degradation products. Dimer ions were also observed for two phosphonate compounds detected in this sample.     

Negative ions generated by reactions with oxygen in the chemical ionization source. I. Characterization of gas-phase and wall-catalyzed reactions of fluorene,anthracene and fluoranthene

The methane negative ion chemical ionization (NICI) mass spectra of polycyclic aromatic hydrocarbons are usually dominated by molecular, M^{? ˙} or M ? H^? ions; however, ions resulting from additions to M have also been reported. Some of these ions have been observed at [M + 14]^{? ˙}, [M + 15]^?, [M + 30]^? and [M + 32]^?˙ and have been attributed to reactions with either oxygen-containing impurities in the buffer gas or alkyl radical species generated by ionization of a hydrocarbon buffer gas. In this study, the NICI spectra of fluorene, anthracene and fluoranthene were studied in detail using quadrupole and Fourier transform mass spectrometers. Spectra were acquired when reactive species such as oxygen, water, nitrous oxide and carbon dioxide were added to the nitrogen buffer gas. Experiments with deuterated methane were also carried out. These studies indicated that buffer gas impurities affect the NICI spectra; however, gas-phase ion-molecule reactions were not responsible for all of the observed products. In addition to electron- and ion-molecule reactions, ions were observed that resulted from wall-catalyzed oxidation reactions followed by electron capture. These reactions were enhanced by the addition of oxygen and elevated ion source temperatures. Depending upon the parent PAH structure, oxidation products such as ketones, quinones and anhydrides were formed.     

Diastereochemical differentiation of bicyclic diols using metal complexation and collision‐induced dissociation mass spectrometry

Metal complex formation was investigated for di‐exo‐, di‐endo‐ and trans‐2,3‐ and 2,5‐disubstituted trinorbornanediols, and di‐exo‐ and di‐endo‐ 2,3‐disubstituted camphanediols using different divalent transition metals (Co²⁺, Ni²⁺, Cu²⁺) and electrospray ionization quadrupole ion trap mass spectrometry. Many metal‐coordinated complex ions were formed for cobalt and nickel: [2M+Met]²⁺, [3M+Met]²⁺, [M–H+Met]⁺, [2M–H+Met]⁺, [M+MetX]⁺, [2M+MetX]⁺ and [3M–H+Co]⁺, where M is the diol, Met is the metal used and X is the counter ion (acetate, chloride, nitrate). Copper showed the weakest formation of metal complexes with di‐exo‐2,3‐disubstituted trinorbornanediol yielding only the minor singly charged ions [M–H+Cu]⁺, [2M–H+Cu]⁺ and [2M+CuX]⁺. No clear differences were noted for cobalt complex formation, especially for cis‐2,3‐disubstituted isomers. However, 2,5‐disubstituted trinorbornanediols showed moderate diastereomeric differentiation because of the unidentate nature of the sterically more hindered exo‐isomer. trans‐Isomers gave rise to abundant [3M–H+Co]⁺ ion products, which may be considered a characteristic ion for bicyclo[221]heptane trans‐2,3‐ and trans‐2,5‐diols. To differentiate cis‐2,3‐isomers, the collision‐induced dissociation (CID) products for [3M+Co]²⁺, [M+CoOAc]⁺, [2M–H+Co]⁺ and [2M+CoOAc]⁺ cobalt complexes were investigated. The results of the CID of the monomeric and dimeric metal adduct complexes [M+CoOAc]⁺ and [2M–H+Co]⁺ were stereochemically controlled and could be used for stereochemical differentiation of the compounds investigated. In addition, the structures and relative energies of some complex ions were studied using hybrid density functional theory calculations. Copyright © 2009 John Wiley & Sons, Ltd.