Reactions of polycyclic aromatic hydrocarbon radical cations with model biological nucleophiles

The determination of gas-phase reactivity of a series of polycyclic aromatic hydrocarbons (PAHs) with nucleophiles is directed at achieving isomer differentiation through ion-molecule reactions and collisionally activated decomposition spectra. A series of PAH isomers form gas-phase [adduci — H]⁺ ions with the reagent nucleophiles pyridine and N-methylimidazole. Collisionally activated decomposition spectra of the [adduct — H]⁺ ions of the pyridine/PAH systems are dominated by products formed by losses of C₅H₄N, C₅H₅N (presumably neutral pyridine), and C₅H₆N. Collisional activation of PAH/N-methylimidazole [adduct — H]⁺ ions causes analogous losses of C₄H₅N₂, C₄H₆N₂ (presumably neutral N-methylimidazole), and C₄H₇N₂. The relative abundances of the ions that result from these losses are highly isomer specific for N-methylimidazole but less so for pyridine. Furthermore, PAH/N-methylimidazole [adduct — H]⁺ ions undergo a series of metastableion decompositions that also provide highly isomer-specific information. The C₄H₇N₂ (from PAH/N-methylimidazole product ions) and C₅H₆N (from PAH/pyridine product ions) losses tend to increase with the ΔH _f of the PAH radical cation. In addition, it is shown that the fragmentation patterns of these gas-phase PAH/nucleophile adducts are similar to fragmentation patterns of PAH/nucleoside adducts generated in solution, which suggests that the structures of products formed in gas-phase reactions are similar to those produced in solution.     

Mass spectral behavior of n-alkynes

The 70 e V-electron impact mass spectra of the C₇–C₁₀ n-alkynes have been determined as well as the metastable ion spectra of the molecular ions and the [CS₂]⁺ and [N₂O]⁺ charge exchange mass spectra of the C₇-C₉ n-alkynes. The metastable ion mass spectra provide only a limited opportunity to distinguish between isomers; however, the 70-eV EI mass spectra of isomeric compounds permit a ready distinction between isomers. The [CS₂]⁺ charge exchange mass spectra of isomeric compounds also show substantial differences. The [N₂O]⁺ charge exchange mass spectra do not show the enhancement of β-fission fragments observed in field ionization experiments, despite representing ions of similar internal energy, and it is concluded that field dissociation is responsible for the β-fission fragments in the field ionization experiments.     

Collisionally induced dissociative ionization of neutral products from ion fragmentations. 2—Collision gas effects and related phenomena

The ion retardation method (whereby an ion beam is prevented from entering a collision gas cell by means of a voltage applied thereto) for permitting the examination of the neutral products of unimolecular ion fragmentations has been extended to include observations of neutral products generated by collisions before the gas cell and their related phenomenology. Observations obtained using an ion beam deflection electrode, an alternative method of preventing the ion beam from entering the collision cell, are also reported. When low collision gas pressures are employed (<2×10^?7 Torr He), this latter method provides collisionally induced dissociative ionization (CIDI) mass spectra of unimolecularly generated neutral fragmentation products, free of complications arising from events induced by collisions occurring outside the collision cell. The CIDI mass spectra of CH₃˙, C₂H₄, CH₃?O, CH₃OH and C₂H₆ generated from positive ion precursors and CH₃˙, CH₃O˙ and C₆H₅NO₂ generated by electron loss from negative ions are described.     

A field ionization and collisionally activated dissociation/charge stripping study of some [C9H10]+˙ ions

The extent of isomerization of [C₉H₁₀]^+˙ ions, with lifetimes of approximately 10^?11 and 10^?6 s has been investigated using field ionization, collisionally activated dissociation and charge stripping techniques. The [C₉H₁₀]^+˙ ions which were investigated included the molecular ions of α-methylstyrene, β-methylstyrene, o-methylstyrene, m-methylstyrene, p-methylstyrene, indan, cyclopropylbenzene, allylbenzene and the product of water loss from 3-phenylpropanol. The field ionization spectra of all the C₉H₁₀ hydrocarbons were different indicating that isomerization to a common ion structure had not occurred to a measurable extent for ions with lifetimes of approximately 10^?11 s. Collisionally activated dissociation and charge stripping results indicated that most of the [C₉H₁₀]^+˙ ions continued to maintain unique ion structures (or mixtures of structures) at ion lifetimes of 10^?6 s. Possible exceptions are the [C₉H₁₀]^+˙ ions from allylbenzene and cyclopropylbenzene which gave indistinguishable collisionally activated dissociation and charge stripping spectra.     

Study on the reactions of fluoroalkanesulfonyl azides with pyrazine and its derivatives

The thermal reactions of fluoroalkanesulfonyl azides R_fSO₂N₃ with pyrazine and its derivatives are studied in detail. All the reactions involved the fluoroalkanesulfonyl nitrene intermediates R_fSO₃N: which was captured by pyrazine to give the pyrazinium N-fluoroalkanesulfonyl ylides C₄NH₄N⁺-⁻NSO₂R_f and hydrogen abstraction product R_fSO₂NH₂, but no corresponding N-pyrazinyl fluoroalkanesulfonyl amide derivatives R_fSO₂NHC₄N₂H₃ were isolated. Excess azides did not afford the bisN-ylide product R_fSO₂N⁻-⁺NC₄H₄N⁺-⁻NSO₂R_f.     

Characterization of N‐Boc/Fmoc/Z‐N′‐formyl‐gem‐diaminoalkyl derivatives using electrospray ionization multi‐stage mass spectrometry

N‐Boc/Fmoc/Z‐N′‐formyl‐gem‐diaminoalkyl derivatives, intermediates particularly useful in the synthesis of partially modified retro‐inverso peptides, have been characterized by both positive and negative ion electrospray ionization (ESI) ion‐trap multi‐stage mass spectrometry (MSⁿ). The MS² collision induced dissociation (CID) spectra of the sodium adduct of the formamides derived from the corresponding N‐Fmoc/Z‐amino acids, dipeptide and tripeptide acids show the [M + Na‐NH₂CHO]⁺ ion, arising from the loss of formamide, as the base peak. Differently, the MS² CID spectra of [M + Na]⁺ ion of all the N‐Boc derivatives yield the abundant [M + Na‐C₄H₈]⁺ and [M + Na‐Boc + H]⁺ ions because of the loss of isobutylene and CO₂ from the Boc protecting function. Useful information on the type of amino acids and their sequence in the N‐protected dipeptidyl and tripeptidyl‐N′‐formamides is provided by MS² and subsequent MSⁿ experiments on the respective precursor ions. The negative ion ESI mass spectra of these oligomers show, in addition to [M‐H]^?, [M + HCOO]^? and [M + Cl]^? ions, the presence of in‐source CID fragment ions deriving from the involvement of the N‐protecting group. Furthermore, MSⁿ spectra of [M + Cl]^? ion of N‐protected dipeptide and tripeptide derivatives show characteristic fragmentations that are useful for determining the nature of the C‐terminal gem‐diamino residue. The present paper represents an initial attempt to study the ESI‐MS behavior of these important intermediates and lays the groundwork for structural‐based studies on more complex partially modified retro‐inverso peptides. Copyright © 2013 John Wiley & Sons, Ltd.     

Collisionally activated dissociation of 2,4,6-triphenylpyridinium cations

Thresholds for the appearance of fragment ions allowed the estimation of threshold fragmentation energies (TFE) for the collisionally activated dissociation (CAD) in the gas phase of laser-desorbed pyridine-ring substituted N-benzylpyridinium cations to form pyridine and a carbocation. p-Methylbenzylpyridinium cation underwent an alternative CAD into pyridinium cation and the p-quinodimethane. The TFE are discussed in comparison with the energy differences (ΔΔH_f = ΔH_f(Py) + ΔH_f(R⁺) ? ΔH_f(Py ⁺R) calculated by the AM1 method to provide strong evidence for benzyl to tropylium cation rearrangement in an ion-molecule pair.     

VUV photoionisation of free azabenzenes: Pyridine, pyrazine, pyrimidine, pyridazine and s-triazine

Photoionisation mass spectrometry was used to obtain the fragmentation pathways of pyridine, pyridazine, pyrimidine, pyrazine and s-triazine molecules upon absorption of 23.0, 15.7 and 13.8 eV synchrotron photons. The ionic fragments observed vary from molecule to molecule, however C₂H₂⁺, HCN⁺and HCNH⁺ are common to all five molecules at the three photon energies. Furthermore, the presence of C₂H₂N₂⁺, C₃H₃N⁺ and C₄H₄⁺ in the spectra of some of the molecules suggests dissociation pathways via loss of HCN moieties. The respective parent cations, m/q=79, 80 and 81 have a greater yield at low photon energies when compared to the most intense fragment peak in each spectra. We recorded two of the fragment cation yields, as well as the parent photoion yield curves of pyridine, pyridazine, and pyrimidine in the 8–30 eV range. The formation of abundant cation fragments show a strong propensity of the molecules for dissociation after the absorption of VUV photons higher than 14 eV. The differences in relative fragment yields from molecule to molecule, and when changing the excitation energy, suggest significant bond rearrangements and nuclear motion during the dissociation time. Thus, bond cleavage is dependent on the photon energy deposited in the molecule and on intramolecular reactivity. With the aid of photoion yield curves and energy estimations we have assigned major peaks in the spectra and discussed their fragmentation pathways.     

Fragmentation of <Emphasis Type="Italic">α</Emphasis>-radical cations of arginine-containing peptides

Fragmentation pathways of peptide radical cations, M^+·, with well-defined initial location of the radical site were explored using collision-induced dissociation (CID) experiments. Peptide radical cations were produced by gas-phase fragmentation of Co^III(salen)-peptide complexes [salen=N,N′-ethylenebis (salicylideneiminato)]. Subsequent hydrogen abstraction from the β-carbon of the side-chain followed by C_α-C_β bond cleavage results in the loss of a neutral side chain and formation of an α-radical cation with the radical site localized on the α-carbon of the backbone. Similar CID spectra dominated by radical-driven dissociation products were obtained for a number of arginine-containing α-radicals, suggesting that for these systems radical migration precedes fragmentation. In contrast, proton-driven fragmentation dominates CID spectra of α-radicals produced via the loss of the arginine side chain. Radical-driven fragmentation of large M^+· peptide radical cations is dominated by side-chain losses, formation of even-electron a-ions and odd-electron x-ions resulting from C_α-C bond cleavages, formation of odd-electron z-ions, and loss of the N-terminal residue. In contrast, charge-driven fragmentation produces even-electron y-ions and odd-electron b-ions.     

Dissociative Photoionization of m-Xylene

The photoionization and dissociative photoionization of m-xylene (C₈H₁₀) were researched by using synchrotron radiation vacuum ultraviolet (SR-VUV) and supersonic expanding molecular beam reflectron time-of-flight mass spectrometer (RFTOF-MS) system. The photoionization efficiency spectra (PIEs) of parent ion C₈H₁₀⁺ and main fragment ions C₈H₉⁺ and C₇H₇⁺ were observed, and the ionization energy (IE) of m-xylene and appearance energies (AEs) of main fragment ions C₈H₉⁺ and C₇H₇⁺ were determined to be 8.60 ± 0.03 eV, 11.76 ± 0.04 eV and 11.85 ± 0.05 eV, respectively. Structures of reactant, transition states (TSs), intermediates (INTs), and products involved in two dominant dissociation channels were optimized at the B3LYP/6-311++G(d,p) level, and the relative energies were calculated at the G3 level. Based on the results, two major dissociative photoionization channels, C₇H₇⁺+CH₃ and C₈H₉⁺+H were calculated at the B3LYP/6-311++G(d,p) level. On the basis of theoretical and experimental results, the dissociative photoionization mechanisms of m-xylene were proposed. The C–H or C–C bond dissociation and hydrogen migration are the main processes in the dissociation channels of m-xylene cation.

     

[M + 11]+˙ and [M + 11]−˙ ions in the nitrogen positive and negative ion chemical ionization mass spectra of aromatic amines

The N₂ negative ion chemical ionization (NICI) mass spectra of aniline, aminonaphthalenes, aminobiphenyls and aminoanthracenes show an unexpected addition appearing at [M + 11]^?˙. This addition is also observed in the N₂ positive chemical ionization (PCI) mass spectra. An ion at [M – 15]^? is found in the NICI spectra of aminoaromatics such as aniline, 1- and 2-aminonaphthalene and 1- and 2-aminoanthracene. Ion formation was studied using labeled reagents, variation of ion source pressure and temperature and examination of ion chromatograms. These experiments indicate that the [M + 11]^?˙, [M – 15]^?˙ and [M + 11]^+˙ ions result from the ionization of analytes altered by surface-assisted reactions. Experiments with ¹⁵N₂, [¹⁵N] aniline, [2,3,4,5,6-²H₅] aniline and [¹³C₆] aniline show that the [M + 11]^?˙ ion corresponds to [M + N – 3H]^?˙. The added nitrogen originates from the N₂ buffer gas and the addition occurs with loss of one ring and two amino group hydrogens. Fragmentation patterns in the N₂ PCI mass spectrum of aniline suggest that the neutral product of the surface-assisted reaction is 1,4-dicyanobuta-1,3-diene. Experiments with diamino-substituted aromatics show analogous reactions resulting in the formation of [M – 4H]^?˙ ions for aromatics with ortho-amino groups. Experiments with methylsubstituted aminoaromatics indicate that unsubstituted sites ortho to the amino group facilitate nitrogen addition, and that methyl groups provide additional sites for nitrogen addition.     

Collision-induced dissociation study of cyclization of α-diazo-ω-arylsulphonylaminoalkan-2-ones

The collision-induced dissociation mass-analysed ion kinetic energy (CID MIKE) spectra (electron impact and chemical ionization) of five α-diazo-ω-arylsulphonylaminoalkan-2-ones and corresponding N-arylsulphonylazetidin-3-ones and N-arylsulphonylpyrrolidin-3-ones were studied. The [M ? N₂]⁺˙ and [MH ? N₂]⁺ ions of two types of the diazo ketones provide CID MIKE spectra similar to those of the corresponding M⁺˙ and MH⁺ of the heterocyclic compounds, i.e. a cyclization analogous to that in solution takes place. For the other three types of diazo compounds the Wolff rearrangement prevails in both the gas and liquid phases. The effect of the substituents on the cyclization process was studied. The data obtained permit the results of acid-catalysed cyclization of similar diazo ketones to be predicted on the basis of their CID MIKE spectra. Chemical ionization provides a closer similarity with reactions in solution than electron impact ionization, which can be rationalized by the protonation of the diazo ketone molecule being the driving force of the cyclization reaction either in solution or in the ion source of a mass spectrometer.     

Charge‐assisted hydrogen bonding in salts of 2‐amino‐1H‐benzimidazole with 3‐phenylpropynoic acid and oct‐2‐ynoic acid

The 100 K structures of two salts, namely 2‐amino‐1H‐benzimidazolium 3‐phenylpropynoate, C₇H₈N₃⁺·C₉H₅O₂⁻, (I), and 2‐amino‐1H‐benzimidazolium oct‐2‐ynoate, C₇H₈N₃⁺·C₈H₁₁O₂⁻, (II), both have monoclinic symmetry (space group P2₁/c) and display N—H...O hydrogen bonding. Both structures show packing with corrugated sheets of hydrogen‐bonded molecules lying parallel to the [001] direction. Two hydrogen‐bonded ring motifs can be identified and described with graph sets R²₂(8) and R⁴₄(16), respectively, in both (I) and (II). Computational chemistry calculations performed on both compounds show that the hydrogen‐bonded ion pairs are more energetically favourable in the crystal structure than their hydrogen–bonded neutral molecule counterparts.     

Fingerprinting stereoisomers by survivor-ion mass spectrometry

Survivor-ion mass spectrometry is used to distinguish stereoisomeric cis- and trans-4-methylcyclohexanol. The method involves producing ions by electron impact ionization and submitting them without mass selection to collisional neutralization and reionization, followed by selective monitoring of non-dissociating ions. The differences in the electron impact mass spectra of the stereoisomers, due to the different fragment ion elemental compositions and structures, are highlighted by collisional neutralization with Xe, NO and CH₃SSCH₃, followed by reionization with oxygen. The differences in the survivor-ion spectra are due to different neutralization efficiencies of the isobaric and isomeric ions produced by electron impact ionization, different stabilities of the intermediate neutral species, different reionization efficiencies and reionized ion stabilities. Neutralization-reionization spectra of the C₇H₁₂^+., C₆H₉⁺, C₃H₆O^+. and C₃H₅O⁺ ions from stereoisomeric 4-methylcyclohexanols are also reported.     

Use of diagnostic neutral losses for structural information on unknown aromatic metabolites: an experimental and theoretical study

This work presents the use of neutral losses (NL) for the identification of compounds related to the metabolism of tyrosine. The mass spectra of all the studied compounds, recorded at several collision energies, are compared. The fragmentation mechanism of protonated molecules, MH⁺, is explained by combining collision‐induced dissociation (CID) mass spectra and density functional theory (DFT) calculations. The results show that the first fragmentation is the elimination from MH⁺ of a neutral molecule including a functional group of the linear chain. Three primary neutral losses are observed: 17 u (NH₃), 18 u (H₂O) and 46 u (H₂O+CO) characterizing amino, hydroxyl and carboxylic functions on the linear chain. The presence and abundance of ions corresponding to these losses are dependent on (i) the position of the functional group on the linear chain, (ii) the initial localisation of the protonating hydrogen, and (iii) the substitution of the aromatic ring. For compounds including a functional group on the benzylic carbon atom, the investigation of the other functions requires the knowledge of secondary fragmentations. Among these secondary fragmentations we have retained the loss of NH₃ from [MH–18u]⁺ and the loss of ketene from [MH–17u]⁺. Experimentally these fragmentations are detected using losses of 35 u and 59/73 u. In other words, NL35 identifies hydroxy and amino compounds and NL 46 and/or NL59/73 identify carboxylic acids. The search for characteristic neutral losses is used for the analysis of compounds in a mixture and the analysis of biological fluid. We show that selective search of several neutral losses allows also the unambiguous differentiation of isomers and gives the opportunity to identify compounds in biological fluids. Copyright © 2008 John Wiley & Sons, Ltd.     

Tetra‐ and hexahydrates of bis(adeninium) zoledronate

The present paper reports the structures of bis(adeninium) zoledronate tetrahydrate {systematic name: bis(6‐amino‐7H‐purin‐1‐ium) hydrogen [1‐hydroxy‐2‐(1H‐imidazol‐3‐ium‐1‐yl)‐1‐phosphonatoethyl]phosphonate tetrahydrate}, 2C₅H₆N₅⁺·C₅H₈N₂O₇P₂²⁻·4H₂O, (I), and bis(adeninium) zoledronate hexahydrate {systematic name: a 1:1 cocrystal of bis(6‐amino‐7H‐purin‐1‐ium) hydrogen [1‐hydroxy‐2‐(1H‐imidazol‐3‐ium‐1‐yl)‐1‐phosphonatoethyl]phosphonate hexahydrate and 6‐amino‐7H‐purin‐1‐ium 6‐amino‐7H‐purine dihydrogen [1‐hydroxy‐2‐(1H‐imidazol‐3‐ium‐1‐yl)ethane‐1,1‐diyl]diphosphonate hexahydrate}, 2C₅H₆N₅⁺·C₅H₈N₂O₇P₂²⁻·6H₂O, (II). One of the adenine molecules and one of the phosphonate groups of the zoledronate anion of (II) are protonated on a 50% basis. The zoledronate group displays its usual zwitterionic character, with a protonated imidazole ring; however, the ionization state of the phosphonate groups of the anion for (I) and (II) are different. In (I), the anion has both singly and doubly deprotonated phosphonate groups, while in (II), it has one singly deprotonated phosphonate group and a partially deprotonated phosphonate group. In (I), the cations form an R₂²(10) base pair, while in (II), they form R₂²(8) and R₂²(10) base pairs. Two water molecules in (I) and five water molecules in (II) are involved in water–water interactions. The presence of an additional two water molecules in the structure of (II) might influence the different ionization state of the anion as well as the different packing mode compared to (I).     

Fluorescence of dissociating fragments from supersonic jet-electron collisions

Supersonically cooled jets of nitrogen, methane, ethane, cyclopropane, and azomethane are crossed with collimated streams of electrons. The CH (B²Σ^? → X²Π) spectra resulting from the electron-induced dissociation of CH₄, C₂H₆, and CH₂)₃ can be fit with rotation temperatures between 4000 and 6000 K for an electron energy of 100 eV. Flourescence spectra of N₂⁺ (B²Σ_w⁺ → X²Π) from the dissociative ionization of azomethane yield a rotational temperature of =8×10³ K; from ionization of molecular nitrogen the rotational temperature of B²Σ_w⁺ N₂⁺ is 45 K. Mechanisms for these various processes are discussed.     

N-phosphoryl amino acids and peptides. Part II: Fast atom bombardment mass spectrometry of N-di-isopropyloxyphosphoryl and N-dibutyloxyphosphoryl amino acids

The positive ion fast atom bombardment mass spectra of N-di-isopropyloxyphosphoryl (Dipp) and N-dibutyloxyphosphoryl (Dbp) amino acids or amino acid methyl esters are presented; and according to the observation of the metastable ions and the high-resolution accurate mass measurement their fragmentation patterns are postulated. Both types of compounds were found to undergo similar fragmentations to produce (HO)₂P(O)N?CH? R + H⁺, in most cases as the most abundant fragment ion of structural significance. An intrinsical difference between the two types of compounds is that N-Dippamino acids appear to favour the successive losses of two molecules of propylene, while the loss of HCOOH seems to be preferred by the Dbp amino acids. For those compounds containing an extra functional group on the side chain of amino acids such as serine or glutamic acid some other type of fragmentation was observed besides the normal phenomenon.     

Matrix-assisted laser desorption/ionization tandem reflectron time-of-flight mass spectrometry of fullerenes

Atandem reflectron time-of-flight mass spectrometer developed in our laboratory provides a unique opportunity to investigate the collision-induced dissociation of fullerene ions formed by matrix-assisted laser desorption/ionization (MALDI). Specifically, this opportunity arises from the ability to utilize high energy collisional activation (normally available only on tandem sector instruments by using continuous ionization techniques) for ions formed by pulsed laser desorption, whereas most MALDI time-of-flight instruments record product ion mass spectra of ions formed by metastable or postsource decay. In this study we investigate the products of mass-selected and collisionally activated C ₆₀ ⁺ and C ₇₀ ⁺ ions by using different target gases over a range of target gas pressures. In general, heavier target gases produce more extensive fragmentation and improve the mass resolution of lower mass ionic products because a greater portion of these ions are formed by single collisions. Additionally, the tandem time-of-flight instrument utilizes a nonlinear (curved-field) reflectron in the second mass analyzer that enables high energy collision-induced dissociation spectra to be recorded without scanning or stepping the reflectron voltage.     

MNDO study of fragmentations in mass spectrometry. Part I. The geometry and electron structure of [C3H6O] + ˙ systems and [C2H3O]+ ions

MNDO calculations of [C₃H₆O]^{+ ˙} predict the parallel existence of both structures of radical cations of acetone (1) and propen-2-ol (2) in electron ionization spectra. The calculated heats of formation of 1^{+ ˙} (ΔH_f^MNDO = 783.2 kj mol^?1) and of 2^{+ ˙} (ΔH_f^MNDO = 649.8 kJ mol^?1) are in very good agreement with the experimental results. A comparison with the results of ab initio calculations (3–21 G and 6–31 G) and experimental data for the individual structures of the main fragment [C₂H₃O]⁺ demonstrates a sufficient accuracy of MNDO results, suggesting the possibility of applying the method also in other cationic systems, especially in larger ones.