Proposed Fragmentation Pathways Research Articles

Effect of the location of hydrogen abstraction on the fragmentation of diuretics in negative electrospray ionization mass spectrometry

The diuretic agents bumetanide, xipamide, indapamide, and related compounds were investigated in order to determine the effect of different ionization sites on their collisionally activated dissociation and the corresponding fragmentation pathways. Therefore, analytes were selectively alkylated, and structural analogues as well as deuterium labeled compounds synthesized, which contain a reduced number of ionizable hydrogen atoms. Thus, specific hydrogen abstractions and their correlated dissociation routes of the negatively charged molecules were eliminated, providing evidence for the influence of the location of ionization on product ion spectra. Fragment ions such as m/ z 78 indicate ionization at the commonly present sulfamoyl residue of diuretics but does not exclude additional ionization sites. Product ion spectra of the investigated diuretic agents proved to be composed by fragmentations initiated from different hydrogen abstractions. Moreover, the generation of radical anions by collision-activated dissociation of even-electron precursor ions was observed, the generation of which is discussed by proposed fragmentation pathways.

Structural characterization and isomer differentiation of chalcones by electrospray ionization tandem mass spectrometry.

A series of chalcones were characterized by electrospray ionization tandem mass spectrometry (MS(n)). Several ionization modes were evaluated, including protonation, deprotonation and metal complexation, with metal complexation being the most efficient. Collision-activated dissociation (CAD) was used to characterize the structures, and losses commonly observed include H(2), H(2)O, CO and CO(2), in addition to methyl radicals for the methoxy-containing chalcones. CAD of the metal complexes, especially [Co(II) (chalcone-H) 2,2'-bipyridine](+), allowed the most effective differentiation of the isomeric chalcones with several diagnostic fragment ions appearing upon activation of the metal complexes. MS(n) experiments were performed to support identification of some fragment ions and to verify the proposed fragmentation pathways. In several cases, MS(n) indicated that specific neutral losses occurred by stepwise pathways, such as the neutral loss of 44 u as CH3* and HCO*, or CH(4) and CO, in addition to CO(2).

Structural studies on ceramides as lithiated adducts by low energy collisional-activated dissociation tandem mass spectrometry with electrospray ionization

We applied electrospray ionization (ESI) tandem quadrupole mass spectrometry to establish the fragmentation pathways of ceramides under low energy collisional-activated dissociation (CAD) by studying more than thirty compounds in nine subclasses. The product-ion spectra of the [M + Li] + ions of ceramides contain abundant fragment ions that identify the fatty acyl substituent and the long-chain base (LCB) of the molecules, and thus, the structure of ceramides can be easily determined. Fragment ions specific to each ceramide subclasses are also observed. These feature ions permit differentiation among different ceramide subclasses. The ion series arising from the classical CC bond cleavages that were reported in the fast-atom bombardment (FAB)-high energy tandem mass spectrometry is not observable; however, the product-ion spectra contain multiple fragment ions informative for structural characterization and isomer identification. We also investigated the tandem mass spectra of the fragment ions generated by in-source CAD (pseudo-MS 3) and of the deuterium-labeling molecular species obtained by H/D exchange to support the ion structure assignments and the proposed fragmentation pathways that lead to the ion formation.

Studies on phosphatidylglycerol with triple quadrupole tandem mass spectrometry with electrospray ionization: fragmentation processes and structural characterization

Negative-ion low-energy collisionally activated dissociation (CAD) tandem mass spectrometry of electrospray-produced ions permits structural characterization of phosphatidylglycerol (PG). The major ions that identify the structures arise from neutral loss of free fatty acid substituents ([M − H − R x CO 2H] −) and neutral loss of the fatty acids as ketenes ([M − H − R x CH = C = O] −), followed by consecutive loss of the glycerol head group. The abundances of the ions arising from neutral loss of the sn-2 substutient as a free fatty acid ([M − H − R 2CO 2H] −) or as a ketene ([M − H − R 2CH = C = O] −) are greater than those of the product ions from the analogous losses at sn-1. Nucleophilic attack of the anionic phosphate site on the C-1 or the C-2 of the glycerol to which the carboxylates attached expels the sn-1 (R 1CO 2 −) or the sn-2 (R 2CO 2 −) carboxylate anion, resulting in a greater abundance of R 2COO − than R 1COO −. These features permit assignments of fatty acid substituents and their position in the glycerol backbone. The results are also consistent with our earlier findings that pathways leading to those losses at sn-2 are sterically more favorable than those at sn-1. Fragment ions at m/ z 227, 209 and 171 reflect the glycerol polar head group and identify the various PG molecules. Both charge-remote fragmentation (CRF) and charge-drive fragmentation (CDF) processes are the major pathways for the formation of [M − H − R x COOH] − ions. The CRF process involves participation of the hydrogen atoms on the glycerol backbone, whereas the CDF process involves participation of the exchangeable hydrogen atoms of the glycerol head group. The proposed fragmentation pathways are supported by CAD tandem mass spectrometry of the analogous precursor ions arising from the H–D exchange experiment, and further confirmed by source CAD in combination with tandem mass spectrometry.

Analysis of diacyl peroxides by Ag + coordination ionspray tandem mass spectrometry: free radical pathways of complex decomposition

Organic peroxides have significance in organic synthesis and biological processes. Characterization of these compounds with weak O–O bonds is sometimes difficult due to their thermal instability and sensitivity to acid or base. Coordination of diacyl peroxides with AgBF 4 provides a means for analysis of these compounds by coordination ionspray tandem mass spectrometry (CIS-MS/MS). Precursor ion (Q 1) scans of acetyl benzoyl peroxide give two Ag + adducts, [M + Ag + solvent] + and [M + Ag + M] +. These silver ion adducts can be selectively dissociated (CID) to give unique structural information about the analyte. Decomposition of the [M + Ag + solvent] + adduct generates fragmentation products due to apparent homolytic cleavage of the O–O bond followed by decarboxylation of the resultant radicals. The bis-diacylperoxide complex, [M + Ag + M] + gives CID pathways that involve homolysis of the O–O bond and free radical cross-coupling of the two diacyl peroxides coordinated to the silver ion, i.e. formation of dibenzoyl peroxide, phenyl benzoate, and biphenyl from acetyl benzoyl peroxide. The observation of free radical CID modes is uncommon in mass spectrometry but these pathways are consistent with well-known solution and gas phase processes for peroxide compounds. The proposed fragmentation pathways have been supported by experiments with 18O and deuterated substrates. This technique can be applied to analyze diacyl peroxides with different substituents as well.

Mass spectrometric analysis of pentafluorobenzyl oxime derivatives of reactive biological aldehydes

We recently demonstrated that a battery of reactive aldehydes can be generated by human neutrophils through the action of myeloperoxidase on α-amino acids. To determine the aldehydes, we formed the pentafluorobenzyloxime (PFBO) derivatives by reacting them with pentafluorobenzylhydroxylamine (PFBHA) and submitting the derivatives to gas chromatography electron-capture mass spectrometry (GC/EC/MS). Two geometric isomers are formed for each of the aldehydes, and they are separable by gas chromatography (GC) and exhibit distinguishable electron-capture (EC) mass spectra. Major fragment ions include [M − HF] · −, which probably has a six-membered ring formed via HF loss from the molecular radical anion. Subsequent decomposition of this intermediate yields other characteristic ions (e.g. those formed by elimination of NO and the anion of m/ z 178). We proposed fragmentation pathways and mechanisms that are consistent with the data derived from collisionally-activated dissociations (CAD) coupled with tandem mass spectrometry, exact-mass measurements, studies of deuterium-labeled analogs, and calculations by PM3 semiemperical and ab initio methods. The generality of the structurally informative fragmentation pattern together with GC separation is the basis of a powerful means for the identification of reactive aldehydes in biological processes and the pathogenesis of disease.

Electron impact fragmentation of carbofuran and its major photolytic transformation metabolites

Mass spectra of carbofuran and its major photo-induced metabolites, 3-hydroxycarbo-furan, ­3-oxocarbofuran and their corresponding phenols, were investigated using electron impact mass spectrometry. Interpretation of the fragmentation pathways, based on the mass spectra, enables structural elucidation and chemical identification of these compounds. The proposed fragmentation pathways and ion structures were verified by exact mass measurements and collision-induced dissociation, wing B/E-linked scanning. The presence of the m/z 137 ion and its B/E-linked scan mass spectrum is unique for 3-hydroxycarbofuran, 3-oxocarbofuran and their corresponding phenols. Thus, this ion can be used to detect the oxidation products at the C3 position of carbofuran. Copyright © 1999 John Wiley & Sons, Ltd.

The Mass Spectral Fragmentation of Perezone and Related Compounds

Electron impact mass spectra of six isomeric compounds, namely perezone, isoperezone, α-pipitzol, β-pipitzol, β-isopipitzol and dihydroisoperezinone have been recorded. The proposed fragmentation pathways leading to the formation of a number of important daughter ions have been confirmed from the corresponding parent ion spectra by collision-induced dissociation (CID) experiments. The elemental composition of the principal fragment ions was determined by accurate mass measurements. © 1997 John Wiley & Sons, Ltd.

Intramolecular aromatic substitution and amino‐Claisen rearrangement in substituted N‐(2‐propynyl)anilines on electron impact

AbstractN‐(2‐Propynyl)anilines undergo amino‐Claisen rearrangement to a minor extent in the ion source, losing a molecule of HCN under electron impact conditions. However, metastable molecular ions with energies closer to threshold undergo Claisen rearrangement giving rise to more abundant [M − HCN]+· ions in the first field‐free region. Loss of a hydrogen from the molecular ion gives rise to the base peak in the mass spectrum of N‐(2‐propynyl)aniline. The hydrogen that is expelled for the formation of the [M − H]+ ion is observed to be from the amino nitrogen, propargylic carbon and the ortho‐carbon of the ring. The last process leads to a cyclic fragment involving intramolecular aromatic substitution. Double oxygen migration from the nitro group to the triple bond, due to the ortho effect, yields an abundant ion at m/z 105 in N‐(2‐propynyl)‐o‐nitroaniline. The proposed fragmentation pathways and ion structures are substantiated by high‐resolution data, B/E and B2/E linked‐scan spectra, collisionally activated dissociation–B/E linked‐scan spectra and deuterium isotopic labelling.

Mass spectra of piperidide and trimethylsilyl ester derivatives of the major metabolite of prostaglandin F

The electron ionization mass spectra of three piperidides and four trimethylsilyl ester derivatives of the major urinary metabolite of prostaglandins F 1α and F 2α (PGF-M) are presented and discussed. The proposed fragmentation pathways are based on substituent shifts, on data from deuterium-labeled methyloxime analogs, and those from pyrrolidide homologs.

The mass spectral fragmentation of copper(II) complexes of cyclic ?-diketones

Electron impact mass spectra of several bis(2-trifluoroacetylcycloalkanonato) copper(II) and bis(2-acetylcycloalkanonato) copper(II) chelates, in which the cyclic β-diketonate moiety comprises five-, six-, seven-, and eight-membered ring systems, have been recorded. Compared with other copper(II) chelates of acyclic β-diketonates, the present series of copper(II) cyclic β-diketonates exhibited more pronounced intramolecular reduction reactions accompanied by a remarkably facile hydrogen migration resulting in the formation of the [LCu(I)-H]+ ion as the base peak in all complexes investigated. The proposed fragmentation pathways leading to the formation of a number of important copper-containing daughter ions have been confirmed by metastable scanning of the corresponding parent ion spectra using the defocusing technique.

Daughter ion mass spectra of 11-pentafluorobenzyl ester derivatives of 11-dehydiothromboxane B2 and B3

Collisionally activated decomposition (CAD) mass spectra of the [M – C6F5CH2⋅]− ions of 1-methyl cster-11-pentafluorobenzyl ester-9,12,15-tris(trimethylsilyl) and 9,12,15-tris(ethyldimethylsilyl) ether derivatives of 11-dehydrothromboxane B2 are presented and discussed. The spectra are interpreted with the aid of those of a corresponding 3,3,4,4-tetradeutero compound and of an analogous derivative of 11-dehydrothromboxane B3. Proposed fragmentation pathways are based on internal consistency of data from all four compounds. The migration of a trimethylsilyl or an ethyldimethylsilyl group is the salient feature of all the CAD spectra.

Claisen rearrangement in phenyl allenyl ethers on electron impact

AbstractPhenyl allenyl ethers undergo Claisen rearrangement under electron impact conditions producing intense [M  CO] ions. Another competing fragmentation pathway in these compounds is an intramolecular aromatic substitution followed by the loss of H˙ or the substituent to give rise to fragments corresponding to benzopyrilium cations. Electron‐withdrawing substituents on the phenyl ring favour the cyclization reaction. An interesting ortho interaction of the nitro group with the allenic moiety leads to the expulsion of CO2 from the molecular ion. The proposed fragmentation pathways and the ion structures are established with the help of linked‐scan spectra (B/E, B2/E), collision activation decomposition spectra and high‐resolution data.

Electron‐impact induced fragmentation of spiro‐1‐pyrazolines

AbstractThe positive‐ion electron impact mass spectra of twelve spiro‐1‐pyrazolines have been recorded as 70 eV electron energy and the dat analyzed to elucidate their fragmentation pathways. None of these compounds gave abundant molecular ions (M+) due to the instability of the pyrazoline ring. The first step in the decomposition of M+ ions is the elimination of a nitrogen molecule followed by a rearrangement resulting in the formation of the cation radical [M–28]+, the decomposition of which is discussed in detail. The proposed fragmentation pathways and their mechanisms are supported by high‐resolution data, linked‐scan measurements at constant B/E and collision‐induced dissociation‐mass‐analyzed ion kinetic energy spectra.

High energy collision‐induced dissociation of alkali‐metal ion adducts of crown ehters and acyclic analogs

High energy collision-induced dissociation (CID) techniques were applied for structural elucidation of alkali-metal ion adducts of crown ethers. The CID of alkali-metal adducts of tetraglyme and hexaethylene glycol were also evaluated to contrast the fragmentation pathways of the cyclic ethers with those of acyclic analogs. A common fragmentation channel for alkali-metal ion adducts of all the ethers, which results in distonic radical cations, is the homolytic cleavage of carbon-carbon bonds. Additionally, dissociation by carbon-oxygen bond cleavages occurs, and these processes are analogous to the fragmentation pathways observed for simple protonated ethers. The proposed fragmentation pathways for alkali-metal ion adducts of crown ethers result mostly in odd-electron, acyclic product ions. Dissociation of the alkali-metal ion adducts of the acyclic ethers is dominated by losses of various neutral species after an initial hydride or proton transfer. The CID processes for all ethers are independent of the alkali-metal ion sizes; however, the extent of dissociation of the complexes to bare alkali-metal ions increases with the size of the metal.

Competing oxygen transfers from nitro group to sulphur and allenic double bonds in allenyl o‐nitrophenyl sulphides on electron impact

AbstractInteresting oxygen transfers from the o‐nitro group to allenic carbons were observed in allenyl o‐nitrophenyl sulphides under electron impact conditions giving rise to abundant fragment ions at m/z 151, 138 and 136. However, a similar oxygen transfer to the sulphur leads to another intense ion at m/z 145. The proposed fragmentation pathways and the ion structures were established through high‐resolution data, collision‐activated dissociation mass‐analysed ion kinetic energy and B/E linked‐scan spectra.

Unusual neutral and radical losses in 2′‐substituted N‐phenylanthranilic acids on electron impact

AbstractUnusual expulsions of [H2O + CO2] from the M+˙ of N‐(o‐carboxyphenyl)anthranilic acid, [H2O + CH2O] from the M+˙ of N‐(o‐methoxyphenyl)anthranilic acid and [H2O + ˙NO2] from the M+˙ of N‐(o‐nitrophenyl) anthranilic acid were observed under electron impact conditions. These processes are stepwise in the corresponding para‐substituted N‐phenylanthranilic acids. The proposed fragmentation pathways and their mechanisms are supported by B/E linked‐scan spectra, collision‐activated decomposition (CAD)–mass‐analysed ion kinetic energy (MIKE) spectra, high‐resolution data, deuterium labelling and chemical substitution.

Ortho Effects in Organic Molecules on Electron Impact. 20. Parallel Oxygen Transfers from Nitro Group to Sulfur and Acetylenic Triple Bond in 3-(o-Nitrophenylthio)-1-propynes

Abstract Oxygen transfers from nitro group to both the sulfur and acetylenic triple bond are noticed in parallel fragmentation pathways during the electron impact induced decompositions of 3-(o-nitrophenylthio)-1-propynes. Single oxygen transfer from nitro group to sulfur leads to abundant ions corresponding to o-nitrosobenzenesulfinyl cation and [M–SO]+· while a concerted double oxygen transfer to sulfur followed by ejection of SO2 from the rearranged molecular ion affords intense quinoline radical cation. Further, a single oxygen transfer to acetylenic triple bond, followed by a simple cleavage produces intense fragments corresponding to o-nitrosobenzenethiol radical cation at m/z 139 and o-nitrosophenylthio cation at m/z 138. The proposed fragmentation pathways and ion structures are established through high-resolution data, collisioninduced dissociation (CID) mass-analyzed ion kinetic energy (MIKE) spectra, B/E linked scan spectra and chemical substitution.

Ortho effects in organic molecules on electron impact: 19—Competing oxygen transfers from nitro group to sulphur and acetylinic carbons in 2‐nitrophenylphenylethynylsulphides

AbstractOxygen transfers to both the acetylenic carbons and sulphur are noticed in parallel fragmentation pathways during the electron‐impact induced decompositions of 2‐nitrophenylphenylethynylsulphides. Single oxygen transfer to acetylinic carbons leads to the most abundant ion corresponding to the benzoyl cation whilst double oxygen transfers to both the acetylenic carbons followed by the ejection of two CO units from the M+˙ ion afford another abundant fragment corresponding to the phenothiazine radical cation. However, the oxygen transfers to sulphur yield a less abundant [M  SO2H]+ ion. The proposed fragmentation pathways and the ion structures are sup ported by high‐resolution data, collision‐induced dissociation Linked‐scan spectra and chemical substitution.

Isomerization of proton‐bound alcohol dimers

AbstractProton‐bound dimers [ROH… \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm H}\limits^ + $\end{document}… HOR] have been studied under chemical ionization conditions. The structures of the fragment ions and the behaviour of variously deuterated ions when R = iC3H7 lead to a proposed fragmentation pathway.