Ionization and fragmentation of monochloro-isomers of 3-hydroxy-2-phenyl-4(1H)-quinolinone

Electron ionization (EI), methane chemical ionization (CI), and collision-induced dissociation (CID) mass spectra of complete series of positional monochloro-isomers of 3-hydroxy-2-phenyl-4(1H)-quinolinone are evaluated and discussed. It is shown that in the CI experiments, in addition to the protonated precursor molecules, odd-electron molecular ions are formed and this affects the appearance of the CID spectra. The influence of different direct probes and other experimental parameters such as the pressure of the reagent gas, isolation width, or collision energy was studied. EI, CI and CID spectra of the positional isomers show essentially the same fragmentation pathways but comparisons of the relative signal intensities of various product ions reveal some positional effects. Different isomers are also distinguished. The compounds can be divided into two groups using diagnostic ions (chloro substitution of the quinolinone moiety or the phenyl ring) or identified using a created spectral database. It was demonstrated that the reproducibility of the CID spectra is fully satisfactory for isomer identification, and that the created database can be applied for comparison of spectra measured over an extended time period (1 month) or spectra obtained during the direct analysis of a reaction mixture extract. Explanation of the fragmentation of the isomers is supported by exploratory density functional theory (DFT) calculations, e.g. rationalization of the relatively higher importance of the M(+.)-H(.)-Cl(.)-CO fragmentation pathway during EI than during CID, and vice versa for the pathway M(+.)-Cl(.)-CO. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Electron and chemical ionization mass spectrometry in stereochemical differentiation of some 1,3-amino alcohols

Mass spectral fragmentations of two cyclopentane, eight cyclohexane and four norbornane/one 1,3-amino alcohols were studied under electron ionization (EI) by low-resolution, high-resolution, metastable ion analysis and collision-induced dissociation (CID) techniques. All stereoisomeric compounds gave rise to identical 70 eV EI mass spectra. However, the spectra of positional isomers clearly differed. The main fragmentation pathway for the saturated compounds began as an α-cleavage reaction with respect to the nitrogen atom. For the norbornene compounds a retro-Diels—Alder reaction was favoured. Relative to the aminomethyl-substituted compounds the fragmentation patterns for the compounds having the amino group connected directly to the ring were more complicated. The chemical ionization (CI) mass spectra were recorded using ammonia, isobutane, methane, dichloromethane and acetone as reagent gas. From the norbornane/One compounds the di-exo isomers decomposed more easily than the di-endo isomers with most of the reagent gases used. Differences between stereoisomers were observed directly only under methane CI. The decomposition products of the [M + H]⁺ ions generated under ammonia and isobutane CI were studies by recording their CID mass spectra. These spectra allowed the differentiation of the stereoisomers, at least to some extent.     

Ultrasonication extraction and gel permeation chromatography clean-up for the determination of polycyclic aromatic hydrocarbons in edible oil by an isotope dilution gas chromatography–mass spectrometry

An analytical method for the determination of US EPA priority pollutant 16 polycyclic aromatic hydrocarbons (PAHs) in edible oil was developed by an isotope dilution gas chromatography–mass spectrometry (GC–MS). Extraction was performed with ultrasonication mode using acetonitrile as solvent, and subsequent clean-up was applied using narrow gel permeation chromatographic column. Three deuterated PAHs surrogate standards were used as internal standards for quantification and analytical quality control. The limits of quantification (LOQs) were globally below 0.5 ng/g, the recoveries were in the range of 81–96%, and the relative standard deviations (RSDs) were lower than 20%. Further trueness assessment of the method was also verified through participation in international cocoa butter proficiency test (T0638) organised by the FAPAS with excellent results in 2008. The results obtained with the described method were satisfying (z ≤ 2). The method has been applied to determine PAH in real edible oil samples.     

Regioisomeric differentiation of 2,3- and 3,4-methylenedioxy ring-substituted phenylalkylamines by gas chromatography/tandem mass spectrometry

Numerous abused drugs of the 3,4-methylenedioxymetamphetamine (MDMA; Ecstasy; N-methyl-1-(3,4-methylenedioxyphenyl)-2-propaneamine) type and various alkyl chain- and aromatic ring-substituted isomers give very similar electron ionization (EI) mass spectra. This seriously affects the analysis of especially ring regioisomeric drug variants. Using collision-induced dissociation (CID) (argon) under EI and chemical ionization, the mass spectra of 18 2,3- and 3, 4-methylenedioxy ring-substituted phenylethylamines were recorded. These techniques permitted an unequivocal differentiation of all studied ring regioisomeric methylenedioxyphenylethylamines. CID mass spectrometry therefore appear to be a reliable tool to establish the kind of ring substitution pattern in regioisomeric methylenedioxyphenalkylamines. Copyright 2000 John Wiley & Sons, Ltd.     

Mass spectral fragmentation pathways in cyclic difluoramino and nitro compounds

The recently synthesized compounds 4, 4-bis(difluoramino)-1-nitropiperidine (I), 1,4,4-trinitropiperidine (II), 1,1,4,4-tetranitrocyclohexane (III), 1,1,4, 4-tetrakis(difluoramino)cyclohexane (IV) and 3,3,7, 7-tetrakis(difluora-mino)octahydro-1,5-dinitro-1,5-diazocine (HNFX, V) are being considered as potential energetic materials. The mass spectra of these compounds were studied using electron ionization (EI) mass spectrometry. A collision-induced dissociation (CID) study of the major EI peaks was carried out using a Finnigan TSQ 700 tandem mass spectrometer. The mass fragmentation pathways are constructed and discussed. The decomposition of HNFX (V), under EI, appeared to parallel the thermal decomposition of nitramines where N-NO(2) cleavage is often the first step. However, the two nitramines with a six-membered ring structure (I and II) underwent initial loss of a geminal substituent; loss of a nitramine nitro group was the secondary step. The two cyclohexane structures (III and IV) showed similar initial fragmentation pathways, featuring successive losses of nitro or difluoramino groups. Copyright 2000 John Wiley & Sons, Ltd.     

Energetics of retro-Diels–Alder fragmentation in limonene as characterized by surface-induced dissociation,and energy- and angle-resolved mass spectrometry

Ionized limonene and related isomeric compounds have been examined by collisional activation at both gaseous and solid targets. The gas-phase collision-induced dissociation (CID) experiments were performed as a function of collision energy and scattering angle and the surface-induced dissociation (SID) experiments as a function of collision energy, in order to vary systematically the internal energy deposited in the molecular ion. The virtual absence of retro-Diels–Alder (RDA) fragmentation upon conventional CID, as compared to its importance in the electron impact (EI) mass spectrum, the subject of a study by Boyd and coworkers, was confirmed. However, as the ion internal energy was increased by raising the collision energy or the scattering angle, RDA fragmentation was observed and it became a dominant mode of fragmentation for SID at collision energies in the range of 25–50 eV. The energy deposited into the colliding ion in the SID technique is compared with that deposited upon CID in the eV and keV energy ranges and upon EI. The order obtained is: SID > EI > low-energy, multiple-collision CID > high-energy, single-collision CID > low-energy, single-collision CID. The distribution of energies in SID is narrower than in the other techniques. High internal energies are accessible by increasing the scattering angle in CID; however, this is accompanied by an increase in the width of the internal energy distribution, and it is therefore not possible to channel fragmentation predominantly into RDA by this method. It is concluded that RDA fragmentation of limonene is a high-energy process and that this is the explanation for its behavior. Isomerization, occurring through 1,3-hydrogen migrations of the molecular ions of limonene, isolimonene, terpinolene and α-terpinene, was investigated and long-lived molecular ions of the first three compounds were found to maintain distinct structures.     

Structure-specific fragmentations of 2,2,4-trisubstituted 1,2-dihydroquinazolines

Fragmentations of a series of 2,2,4-trisubstituted 1,2-dihydroquinazolines were studied by electron impact (EI) ionization and positive- and negative-ion fast atom bombardment (FAB) coupled with collision-induced decomposition (CID). The EI mass spectra give information that directly indicates the specific location of each substituent. The FAB–CID spectra provide data regarding the masses of each substituent, but no definitive information regarding location.     

Stereospecific fragmentations in the mass spectra of stereoisomeric isoindoloquinazolines

The mass spectrometric behavior of stereo- and regioisomeric, partially saturated isoindoloquinazolines was studied by positive-ion electron ionization (EI) and fast-atom bombardment (FAB/LSIMS) mass spectrometry combined with collision-induced dissociation (CID). A highly stereospecific retro-Diels-Alder process was observed in the cyclohexene-fused isomers under the EI conditions, and a corresponding (although less specific) fragmentation was observed in their FAB spectra. In the absence of RDA fragmentations, regio- and stereoisomers of the cyclohexane-fused heterocycles could be distinguished based on their FAB/CID spectra.     

Elucidation of urinary metabolites of fluoxymesterone by liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry

The suitability of liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) for the elucidation of fluoxymesterone metabolism has been evaluated. Electrospray ionization (ESI) and collision induced dissociation (CID) fragmentation in LC-MS/MS and electron impact spectra (EI) in GC-MS have been studied for fluoxymesterone and two commercially available metabolites. MS(n) experiments and accurate mass measurements performed by an ion-trap analyser and a QTOF instrument respectively have been used for the elucidation of the fragmentation pathway. The neutral loss scan of 20 Da (loss of HF) in LC-MS/MS has been applied for the selective detection of fluoxymesterone metabolites. In a positive fluoxymesterone doping control sample, 9 different analytes have been detected including the parent compound. Seven of these metabolites were also confirmed by GC-MS including 5 previously unreported metabolites. On the basis of the ionization, the CID fragmentation, the accurate mass of the product ions and the EI spectra of these analytes, a tentative elucidation as well as a proposal for the metabolic pathway of fluoxymesterone has been suggested. The presence of these compounds has also been confirmed by the analysis of five other positive fluoxymesterone urine samples.     

Mass spectrometry of coordination compounds of transition metals with tetradentate ligands. 11. isomeric quasi-macrocyclic Ni(II) complexes based on S-substituted isothiocarbohydrazides and the structure of “small” ions derived from them

Two series of bonding isomers of Ni(II) coordination compounds with tetradentate quasimacrocyclic ligands based on S-substituted isothiocarbohydrazides were characterized by electron impact (EI) mass spectrometry and by tandem mass spectrometry methods. Conventional EI mass spectra were more isomer specific than metastable ion (MI) and collision induced dissociation (CID) mass spectra of the molecular ions. The MI (and CID) mass spectra of the isomers were very similar. This effect resulted from a facile randomization of Ni–N bonds in the ions possessing low internal energies, prior to their dissociation. The compounds were found to be convenient precursors for coordinatively unsaturated metal-containing ions, [NiL_n]⁺ and [RNiL_n]⁺ (n = 1, 2; L = NCCH₃, NCSCH₃; R = OH, NO). Most of these species had a structure of mono- or disolvated nickel ion. The dissociation of [HONiNCCH₃]⁺ ions was consistent with the formation of two isomers: one corresponding to the [HONi]⁺ ion solvated by acetonitrile and the other is a complex of H₂O with [NiNCCH₂]⁺. A structure of [HO,Ni,(NCCH₃)₂]⁺ ions was best represented by a five-membered cycle formed by two acetonitrile units and the metal atom with the OH group attached to one of the nitrogen atoms.     

Liquid chromatography-mass spectrometry with collision-induced dissociation of conjugated metabolites of benzol[a]pyrene

Benzo[a]pyrene (BP) metabolites conjugated with glutathione, cysteine-glycine, cysteine, N-acetylcysteine, and sulfuric and glucuronic acids have been studied by microcolumn liquid chromatography-electrospray mass spectrometry with collision-induced dissociation (CID) on a hybrid double focusing magnetic sector-orthogonal time-of-flight tandem mass spectrometer equipped with a focal plane array detector. Negative-ion electrospray mass spectra of the conjugated BP metabolites showed strong [M – H]^? ions. When the array detector was used, spectra were obtained from femtomoles of sample infused at mass resolutions of 5000 (full width at half maximum). Cone voltage fragmentation spectra show [M-H]^? ions and fragment ions indicative of the BP moiety and/or the conjugating group. Linked scan CID spectra at constant B/E were found to contain structurally informative product ions from infusion of as little as 1 pmol of sample. CID spectra were also recorded by using the double focusing sectors for precursor ion selection and the orthogonal time-of-flight analyzer for product ion mass separation. The method was applied to the analysis of conjugated BP metabolites in the urine of germ-free rats given a single intraperitoneal dose of BP.     

Analysis of 7 Dinitroaniline Residues in Complex Food Matrices by GC–NCI/MS

A modified quick, easy, cheap, effective, rugged, and safe sample preparation method combined with gas chromatography–negative chemical ionization–mass spectrometry (GC–NCI/MS) has been developed for the determination of 7 dinitroaniline herbicide residues in complex matrices (garlic, olive oil, scallion, leek and chili). Dinitroaniline residues were extracted with hexane-saturated acetonitrile. After the cleanup with the dispersive solid-phase extraction, the extract was analyzed by GC–NCI/MS in selected ion monitoring mode. Two isotope internal standards (trifluralin-d ₁₄ and pendimethalin-d ₅) were employed for quantification. Compared with electron ionization (EI) mode, the superiorities of NCI in sensitivity and selectivity were investigated. Limits of the detection of 7 dinitroanilines were in the range of 0.014–0.096 μg kg^?1, and there were no interfering peaks (unlike in EI) in the complex matrices. Recoveries of 7 dinitroanilines in five matrices at three spiked levels (10, 20 and 40 μg kg^?1) ranged from 61 to 126 % and the relative standard deviations were all below 12 %.     

The even-electron rule in electrospray mass spectra of pesticides

A study of the fragmentation and ion formation of three major families of pesticides (including herbicides, insecticides, and fungicides) by liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS) and liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF-MS) was carried out using positive electrospray ionization (ESI) and the results compared with those by gas chromatography (GC)/TOF-MS with electron ionization (EI) in order to test the validity of the even-electron rule in electrospray ionization. First, the majority of the fragmentations by positive ion ESI were even electron (EE) ions (93% of the fragment ions). Secondly, the formation of odd-electron (OE) fragment ions was greater with EI, where the fragment ions were present in a ratio of approximately 1:2 (35% OE ions and 65% EE ions). Thirdly, in-source collision-induced dissociation (CID) fragmentation by LC/TOF-MS and CID fragmentation in the collision cell by LC/Q-TOF-MS/MS resulted in 95% of the fragment ions being identical between the two types of fragmentation. As ESI in the positive ion mode yields an EE precursor ion (normally a protonated molecule), this commonly leads to EE fragment ions by elimination of molecules - a process called the even-electron rule. Neutral radical losses were less common in ESI but were common in the EI spectra of the same compounds. The structures that did lead to OE ions in ESI (exceptions to the even-electron rule approximately 7% of all ESI ions) favored electronegative radical losses in approximately the following order: .SO(2)CH(3), .NO(2), .CH(3), .Cl, .SCH(3), .CH(2)CH, and .OH.     

Simultaneous multidetermination of residues of pesticides and polycyclic aromatic hydrocarbons in olive and olive-pomace oils by gas chromatography/tandem mass spectrometry

A multiresidue method for determining major pesticides and polycyclic aromatic hydrocarbons (PAHs) in olive oils in a single injection by use of gas chromatography/tandem mass spectrometry (GC-MS/MS) is proposed. Samples are previously extracted with an acetonitrile/n-hexane mixture and cleaned up by gel permeation chromatography. Electron ionization and chemical ionization allow pesticides and PAHs to be determined in a single analysis. The precision obtained was quite satisfactory (relative standard deviations ranged from 3 to 7.8%), and so were recoveries (84-110%). The linear relation was observed from 1 to 500 microg/kg for pesticides and 0.3 to 200 microg/kg for PAHs; also, the determination coefficient, R(2), was better than 0.995 in all instances. The proposed method was applied to the routine analysis of PAH and pesticide residues in virgin and refined olive oil and olive-pomace oil samples.     

In situ reversible tuning of chemical interface damping in single gold nanorod-based recyclable platforms through manipulation of supramolecular host–guest interactions

Recently, chemical interface damping (CID) has been proposed as a new plasmon damping pathway based on interfacial hot-electron transfer from metal to adsorbate molecules. It has been considered essential, owing to its potential implications in efficient photochemical processes and sensing experiments. However, thus far, studies focusing on controlling CID in single gold nanoparticles have been very limited, and in situ reversible tuning has remained a considerable challenge. In these scanning electron microscopy-correlated dark-field spectroscopic measurements and density functional theory calculations, cucurbit[7]uril (CB[7])-based host–guest supramolecular interactions were employed to examine and control the CID process using monoamine-functionalized CB[7] (CB[7]-NH₂) attached to single gold nanorods (AuNRs). In situ tuning of CID through the CB[7]–oxaliplatin complexation, which can result in the variation of the chemical nature and electronic properties of adsorbates, was presented. In addition, in situ tuning of CID was demonstrated through the competitive release of the oxaliplatin guest from the oxaliplatin@CB[7] complex, which was then replaced by a competitor guest of spermine in sufficient amounts. Furthermore, nuclear magnetic resonance experiments confirmed that the release of the guest is the consequence of adding salt (NaCl). Thus, in situ reversible tuning of CID in single AuNRs was achieved through successive steps of encapsulation and release of the guest on the same AuNR in a flow cell. Finally, single CB[7]-NH₂@AuNRs were presented as a recyclable platform for CID investigations after the complete release of guest molecules from their host–guest inclusion complexes. Therefore, this study has paved a new route to achieve in situ reversible tuning of CID in the same AuNR and to investigate the CID process using CB-based host–guest chemistry with various guest molecules in single AuNRs for efficient hot-electron photochemistry and biosensing applications.

This study has paved a new route to achieve in situ reversible tuning of chemical interface damping (CID) in the same gold nanorod (AuNR) and to investigate the CID process using cucurbituril (CB)-based host–guest chemistry with various guest molecules in single AuNRs.     

Tandem mass spectrometry investigation of ADP-ribosylated kemptide

Bacterial adenosine diphosphate-ribosyltransferases (ADPRTs) are toxins that play a significant role in pathogenicity by inactivating host proteins through covalent addition of ADP-ribose. In this study we used ADP-ribosylated Kemptide (LRRASLG) as a standard to examine the effectiveness of three common tandem mass spectrometry fragmentation methods for assignment of amino acid sequence and site of modification. Fragmentation mechanisms investigated include low-energy collision-induced dissociation (CID), infrared multiphoton dissociation (IRMPD), and electron-capture dissociation (ECD); all were performed on a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer. We show that ECD, but neither CID nor IRMPD, of ADP-ribosylated Kemptide produces tandem mass spectra that are interpretable with regard to amino acid sequence assignment and site of modification. Examination of CID and IRMPD tandem mass spectra of ADP-ribosylated Kemptide revealed that fragmentation was primarily focused to the ADP-ribose region, generating several potential diagnostic ions for use in discovery of ADP-ribosylated proteins. Because of the lower relative sensitivity of ECD during data-dependent acquisition to CID, we suggest a 2-fold strategy where CID and IRMPD are first used to detect ADP-ribosylated peptides, followed by sequence assignment and location of modification by ECD analysis.     

The structure of ionized 1,5 hexadiene in the gas phase

The structure of ionized 1,5-hexadiene, prepared by charge transfer between 1,5-hexadiene and CS2+*, is examined using energy-resolved collision-induced dissociation (CID). By comparing the product distributions and product appearance curves with those of authentic low-energy C6H10+* ions, it is determined that 1,5-hexadiene cation spontaneously rearranges to cyclohexene cation in the gas-phase. The proposed mechanism for formation of cyclohexene cation in the gas phase is analogous to that determined for this process under matrix isolation conditions, where it proceeds via a Cope rearrangement to the cyclohexane-1,4-diyl cation, followed by isomerization to cyclohexene cation. It is shown that electron ionization (EI) of 1,5-hexadiene gives a different molecular ion than is obtained upon chemical ionization (CI). The energy-resolved CID mass spectrum for the EI product is consistent with what would be obtained for a mixture of low energy ion isomers.     

Quantitation of isomeric ethyl pyridine mixtures by multivariate calibration applied to ion-molecule reaction/collision-induced dissociation triple-stage mass spectra

In reactions of the distonic ion ⁺CH₂OCH₂ with the three isomeric ethyl pyridines, ionized methylene transfer occurs readily yielding distonic N-methylene-ethylpyridinium ions. On-line mass selection and 10 eV collision-induced dissociation (CID) of the CH₂⁺ transfer products yields characteristic fragment ions, which are formed via processes greatly influenced by the ortho, meta or para location of the ethyl substituent in the pyridine ring. Quantitation of mixtures of isomeric 2-, 3-, and 4-ethyl pyridines of varying compositions was then performed by multivariate calibration in the form of the partial least square (PLS) model applied to both single-stage (MS) 70 eV electron ionization (EI) and pentaquadrupole triple-stage sequential ion-molecule reaction/CID product ion mass spectra. The results exemplify the superior ability of combined chemometric analysis and sequential mass spectrometric techniques, which benefits from both characteristic ion chemical reactivity and dissociation behavior, for rapid and accurate quantitation of complex isomeric mixtures.     

Mass spectral study of meso-alkyl and meso-cycloalkyl calix(4)pyrroles under electron impact conditions

A series of meso-cycloalkyl calix(4)pyrroles (I) and meso-dialkyl calix(4)pyrroles (II) has been studied under electron ionization (EI) mass spectral conditions. All the calix(4)pyrroles showed prominent molecular ions. The cleavage of the C--C bond linked at position 2 of the pyrrole ring (beta-cleavage) is the foremost and dominant fragmentation process. The beta-cleavage process, either through ring opening or directly, results in the loss of an alkyl radical from the molecular ion. The collision-induced dissociation (CID) spectra of I showed specific sequential expulsion of pyrrole and/or cycloalkyl rings from the molecular ion with or without hydrogen migrations, revealing more information on the structure of individual compounds than was available from the EI spectra. The isomeric cycloalkyl calix(4)pyrroles showed distinguishable CID spectra, indicating structure specificity in initial ring opening whereas, in the case of II, the EI mass spectrum contains all the structure-indicative fragment ions. The CID spectra of II resulted in a dominant [M-R]+ ion, with other characteristic ions being less abundant.