Characterizing the electrospray ionization mass spectral fragmentation pattern of indole derivatives synthesized from 2-keto glycosides

Four indole derivatives synthesized from 2-keto glycosides were analyzed by electrospray ionization tandem mass spectrometry (ESI-MSn) with low-energy collision-induced dissociation to establish a general structural elucidation of indole derivatives. Their fragmentation pathways are proposed on the basis of the MSn studies and deuterium-labeled experiments. Indole derivatives undergo complicated gas-phase rearrangements in addition to simple bond cleavages. A rearrangement, which involves a contraction of the six-membered ring, was observed and a mechanism was proposed. The observations may have some potential applications in the interpretation of the mass spectra of indole derivatives.     

Desorption electrospray ionization mass spectrometry of DNA nucleobases: implications for a liquid film model

Desorption electrospray ionization (DESI) mass spectrometry has been implemented on a commercial ion‐trap mass spectrometer and used to optimize mass spectrometric conditions for DNA nucleobases: adenine, cytosine, thymine, and guanine. Experimental parameters including spray voltage, distance between mass spectrometer inlet and the sampled spot, and nebulizing gas inlet pressure were optimized. Cluster ions including some magic number clusters of nucleobases were observed for the first time using DESI mass spectrometry. The formation of the cluster species was found to vary with the nucleobases, acidification of the spray solvent, and the deposited sample amount. All the experimental results can be explained well using a liquid film model based on the two‐step droplet pick‐up mechanism. It is further suggested that solubility of the analytes in the spray solvent is an important factor to consider for their studies by using DESI. Copyright © 2009 John Wiley & Sons, Ltd.     

食品中化学性有害物的质谱软电离裂解规律及筛查技术研究进展

食品中化学性有害物是导致食品安全问题的重要原因,质谱是对食品中化学性有害物进行定性定量分析的有效方法。该文按照化合物结构类别,综述了食品中重要化学性有害物的质谱软电离裂解机理,包括农药、兽药、真菌毒素,以及其他化学污染物。对于每类化合物,重点综述化合物质谱裂解产生的特征碎片、中性丢失等,以及这些质谱软电离裂解机理在食品中化学性有害物筛查及发现中的应用。研究化合物的质谱裂解机理可以帮助研究者对化合物进行结构解析和结构确证,为食品中同类结构新型化学性有害物的发掘提供理论依据。     

An experimental and computational investigation on the fragmentation behavior of enaminones in electrospray ionization mass spectrometry

The dissociation pathways of protonated enaminones with different substituents were investigated by electrospray ionization tandem mass spectrometry (ESI‐MS/MS) in positive ion mode. In mass spectrometry of the enaminones, Ar? CO? CH?CH? N(CH₃)₂, the proton transfers from the thermodynamically favored site at the carbonyl oxygen to the dissociative protonation site at ipso‐position of the phenyl ring or the double bond carbon atom adjacent to the carbonyl leading to the loss of a benzene or elimination of C₄H₉N, respectively. And the hydrogen? deuterium (H/D) exchange between the added proton and the proton of the phenyl ring via a 1,4‐H shift followed by hydrogen ring‐walk was witnessed by the D‐labeling experiments. The elemental compositions of all the ions were confirmed by ultrahigh resolution Fourier transform ion cyclotron resonance tandem mass spectrometry (FTICR‐MS/MS). The enaminones studied here were para‐monosubstituted on the phenyl ring and the electron‐donating groups were in favor of losing the benzene, whereas the electron‐attracting groups strongly favored the competing proton transfer reaction leading to the loss of C₄H₉N to form a benzoyl cation, Ar‐CO⁺. The abundance ratios of the two competitive product ions were relatively well‐correlated with the σ_p⁺ substituent constants. The mechanisms of these reactions were further investigated by density functional theory (DFT) calculations. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparison of the sensitivity of mass spectrometry atmospheric pressure ionization techniques in the analysis of porphyrinoids

The porphyrinoids chemistry is greatly dependent on the data obtained in mass spectrometry. For this reason, it is essential to determine the range of applicability of mass spectrometry ionization methods. In this study, the sensitivity of three different atmospheric pressure ionization techniques, electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization, was tested for several porphyrinods and their metallocomplexes. Electrospray ionization method was shown to be the best ionization technique because of its high sensitivity for derivatives of cyanocobalamin, free‐base corroles and porphyrins. In the case of metallocorroles and metalloporphyrins, atmospheric pressure photoionization with dopant proved to be the most sensitive ionization method. It was also shown that for relatively acidic compounds, particularly for corroles, the negative ion mode provides better sensitivity than the positive ion mode. The results supply a lot of relevant information on the methodology of porphyrinoids analysis carried out by mass spectrometry. The information can be useful in designing future MS or liquid chromatography–MS experiments. Copyright © 2013 John Wiley & Sons, Ltd.     

H NMR, C NMR and mass spectral studies of some Schiff bases derived from 3-amino-1,2,4-triazole

Heterocyclic Schiff bases derived from 3-amino-1,2,4-triazole and different substituted aromatic aldehydes are prepared and subjected to ¹H NMR, ¹³C NMR and mass spectral analyses. ¹H NMR spectra in DMSO exhibit a sharp singlet within the 9.35–8.90 ppm region which corresponds to the azomethine proton. The position of this signal is largely dependent on the nature of the substituents on the benzal moiety. It is observed that the shape, position and the integration value of the signal of the aromatic proton of the triazole ring (⁵C) are clearly affected by the rate of exchange, relaxation time, concentration of solution as well as the solvent used. ¹³C NMR is taken as substantial support for the results reached from ¹H NMR studies. The mass spectral results are taken as a tool to confirm the structure of the investigated compounds. The base peak (100%), mostly the M-1 peak, indicates the facile loss of hydrogen radical. The fragmentation pattern of the unsubstituted Schiff base is taken as the general scheme. Differences in the other schemes result from the effect of the electronegativity of the substituents attached to the aromatic ring.     

Assessment of the various ionization methods in the analysis of metal salen complexes by mass spectrometry

Metal salen complexes are one of the most frequently used catalysts in enantioselective organic synthesis. In the present work, we compare a series of ionization methods that can be used for the mass spectral analysis of two types of metalosalens: ionic complexes (abbreviated as Com⁺X^?) and neutral complexes (NCom). These methods include electron ionization and field desorption (FD) which can be applied to pure samples and atmospheric pressure ionization techniques: electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) which are suitable for solutions. We found that FD is a method of choice for recording molecular ions of the complexes containing even loosely bonded ligands. The results obtained using atmospheric pressure ionization methods show that the results depend mainly on the structure of metal salen complex and the ionization method. In ESI spectra, Com⁺ ions were observed, while in APCI and APPI spectra both Com⁺ and [Com + H]⁺ ions are observed in the ratio depending on the structure of the metal salen complex and the solvent used in the analysis. For complexes with tetrafluoroborate counterion, an elimination of BF₃ took place, and ions corresponding to complexes with fluoride counterion were observed. Experiments comparing the relative sensitivity of ESI, APCI and APPI (with and without a dopant) methods showed that for the majority of the studied complexes ESI is the most sensitive one; however, the sensitivity of APCI is usually less than two times lower and for some compounds is even higher than the sensitivity of ESI. Both methods show very high linearity of the calibration curve in a range of about 3 orders of magnitude of the sample concentration. Copyright © 2014 John Wiley & Sons, Ltd.     

The effect of electron-withdrawing properties of substituents on the hydrolysis of some Schiff bases

The dissociation kinetics of the Schiff bases investigated in the present paper [N,N-bis(X-benzylidenes)ethylenediamine], have been examined under basic and acidic conditions, in aqueous medium 25% acetone in water (wt-wt). The base hydrolysis reaction of these compounds was found to follow second-order kinetics, first-order with respect to each of the Schiff base and the hydroxide ions. The rate-determining step is suggested to be the hydroxide ions attack on the free base. The effect of acetone ratio, in hydrolysis medium, has been studied under alkaline conditions. It is deduced that both the hydrogen bonding formation and solvent-solvent interaction have a pronounced role in such hydrolysis reactions. The acid hydrolysis reaction is strictly second-order kinetics, first-order with respect to the Schiff base and also to the hydrogen ions, and the attack of water molecules on the protonated substrate becomes the rate-determining step. A slower rate of the base hydrolysis was observed through the Schiff base II (p-NO₂), on the other hand, a fast acid hydrolysis rate was detected in the case of compound III (p-COOH). Furthermore, from the effect of temperature on the reaction rate, the various thermodynamic parameters have been also calculated and discussed.     

Degrees of freedom effect on fragmentation in tandem mass spectrometry of singly charged supramolecular aggregates of sodium sulfonates

The characteristic collision energy (CCE) to obtain 50% fragmentation of positively and negatively single charged noncovalent clusters has been measured. CCE was found to increase linearly with the degrees of freedom (DoF) of the precursor ion, analogously to that observed for synthetic polymers. This suggests that fragmentation behavior (e.g. energy randomization) in covalent molecules and clusters are similar. Analysis of the slope of CCE with molecular size (DoF) indicates that activation energy of fragmentation of these clusters (loss of a monomer unit) is similar to that of the lowest energy fragmentation of protonated leucine–enkephalin. Positively and negatively charged aggregates behave similarly, but the slope of the CCE versus DoF plot is steeper for positive ions, suggesting that these are more stable than their negative counterparts. Copyright © 2013 John Wiley & Sons, Ltd.     

An unprecedented ortho effect in mass spectrometric fragmentation of even-electron negative ions from hydroxyphenyl carbaldehydes and ketones

A mass spectrometric peak for a carboxylate anion is observed in collision-induced dissociation (CID) mass spectra recorded from negative ions derived from ortho isomers of hydroxyphenyl carbaldehydes and ketones. For example, CID spectra of 2-hydroxy derivatives of benzaldehyde, acetophenone, propiophenone, isobutyrophenone, and pivalophenone show peaks at m/z 45, 59, 73, 87, and 101 for the formate, acetate, propionate, isobutyrate, and pivalate anions, respectively.     

Negative-mode MALDI mass spectrometry for the analysis of pigments using tetrathiafulvalene as a matrix

Negative-mode matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) analysis of industrial pigments was performed using tetrathiafulvalene (TTF), an electron donating compound, as a matrix. Comparing with other matrices such as tetracyanoquinodimethane (TCNQ), dithranol, 2-hydroxy-6-nitroaniline (HNA), and harmine hydrochloride, the most abundant analyte ions were produced by the TTF as radical or deprotonated anions. In addition, fragment ions in the negative mode of operation are also found to be much less abundant than those in the positive mode of operation.     

Positive chemical ionization triple‐quadrupole mass spectrometry and ab initio computational studies of the multi‐pathway fragmentation of phthalates

We report the first positive chemical ionization (PCI) fragmentation mechanisms of phthalates using triple‐quadrupole mass spectrometry and ab initio computational studies using density functional theories (DFT). Methane PCI spectra showed abundant [M + H]⁺, together with [M + C₂H₅]⁺ and [M + C₃H₅]⁺. Fragmentation of [M + H]⁺, [M + C₂H₅]⁺ and [M + C₃H₅]⁺ involved characteristic ions at m/z 149, 177 and 189, assigned as protonated phthalic anhydride and an adduct of phthalic anhydride with C₂H₅⁺ and C₃H₅⁺, respectively. Fragmentation of these ions provided more structural information from the PCI spectra. A multi‐pathway fragmentation was proposed for these ions leading to the protonated phthalic anhydride. DFT methods were used to calculate relative free energies and to determine structures of intermediate ions for these pathways. The first step of the fragmentation of [M + C₂H₅]⁺ and [M + C₃H₅]⁺ is the elimination of [R? H] from an ester group. The second ester group undergoes either a McLafferty rearrangement route or a neutral loss elimination of ROH. DFT calculations (B3LYP, B3PW91 and BPW91) using 6‐311G(d,p) basis sets showed that McLafferty rearrangement of dibutyl, di(‐n‐octyl) and di(2‐ethyl‐n‐hexyl) phthalates is an energetically more favorable pathway than loss of an alcohol moiety. Prominent ions in these pathways were confirmed with deuterium labeled phthalates. Copyright © 2010 John Wiley & Sons, Ltd.     

Improvement using chemometrics in ion mobility coupled to mass spectrometry as a tool for mass spectrometry fragmentation studies: Flavonoid aglycone cases

A chemometric method for the treatment of ion mobility coupled to mass spectrometry (IMS/MS) data is proposed as a complementary tool for obtaining experimental evidence for the study of MS fragmentations, which can provide a direct and automatable methodology for characterising ionic series and the hierarchy of all product ions of an MS spectrum.     

Electron ionization-induced fragmentation of R2N2Fe2(CO)6 complexes with distinct geometries of the tetrahedral core: investigation of mu-1,2-(1,2-diaza-3-methylcyclopentane)diylbis(tricarbonyliron) and bis(mu2-acetophenoniminato)bis(tricarbonyliron)

Two binuclear bis(tricarbonyliron) title complexes with N(2)Fe(2) tetrahedral cores, 1 and 2, respectively, which show different molecular folding resulting from the appearance (in 1), and absence (in 2) of the N-N sigma-bond, were compared in terms of mass spectral fragmentation routes. A multipath fragmentation noted for the molecule 1 revealing internal stress contrasts with the single-route fragmentation of 2. The fragmentation paths resulting from the admixtures were defined and analyzed from the fragment ion B/E and parent ion B(2)/E linked scan spectra.     

Double cation adduction in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of electron deficient anthraquinone derivatives

Six anthraquinone derivatives were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). Clear (pseudo) molecular ions were observed for all the compounds. Interestingly, for some derivatives, strong ions with double cation adduction were also recorded in the positive mode. It is remarkable that all these ions are singly charged. In this work, possible mechanisms for the double cation adduction were investigated and discussed. It appears that the double cation adduction was due to the electron deficient nature of the derivatives, and formed by taking up two singly charged cations and one electron. Substituents on the anthraquinone ring were found to have a significant effect on the double cation adduction. In contrast, no considerable influence of the acidity of MALDI matrix/solution was observed, even on the double proton adduction. Furthermore, it was demonstrated that double cation adduction might occur in the MALDI gas-phase plume. In addition to the anthraquinones, three more electron deficient compounds of different types, i.e. a perylene bisimide derivative (PB), 3,7-decanoylamino-4,8-dihydrobenzo[1,2-b:4,5-b']dithiophene-4,8-dione (TQ) and 6,6-phenyl C61-butyric acid methyl ester (PCBM), were also analyzed with MALDI TOF MS. The results indicate that the 'abnormal' double cation adduction might be a 'normal' phenomenon in the MALDI TOF MS analysis of many electron deficient compounds.     

Origin of the conformation dependence of protein charge-state distributions in electrospray ionization mass spectrometry

The influence of tertiary structure on the electrospray ionization mass spectra of proteins is a well known and broadly exploited phenomenon. However, the underlying mechanism is not well understood. This paper discusses the bases and the implications of the two current hypotheses (solvent accessibility and Coulombic repulsions), pointing out the remaining open questions. Evidence reported here supports a third hypothesis, i.e. that intramolecular interactions in folded proteins play a key role in determining the observed charge-state distributions. It is proposed that native protein structures stabilize to a large extent pre-existing charges of the opposite polarity to the net charge of the ion, preventing their neutralization during the electrospray process. Thus, the higher charge states of unfolded conformations, relative to the folded structure, would not derive from a more extensive ionization of the former, but rather from a higher content of neutralizing charges in the latter. This interpretation allows several other problematic observations to be explained, including the different shapes of the spectra of folded and unfolded proteins, the discrepancies between observed and predicted gas-phase reactivity of protein ions and the apparent inconsistency of positive- and negative-ion mode results.     

基质辅助激光解吸电离质谱和电喷雾电离质谱在辣根过氧化物酶糖肽结构分析中的应用

糖链结构的质谱解析是今后糖蛋白分析中的重要研究内容,其中完整糖肽的分析,由于可以同时获得糖基化位点和对应糖链的结构信息,更具有重要意义和研究前景。本工作对质谱软电离技术在完整糖肽分析中的应用进行了研究,其中包括了基质辅助激光解吸电离(matrix-assisted laser desorption ionization, MALDI)和电喷雾电离(electrospray ionization, ESI)技术。通过平行使用两种串联质谱(tandem mass spectrometry, MS/MS)分析策略: MALDI-MS/MS和ESI-MS/MS对目标糖蛋白——辣根过氧化物酶进行分析,并讨论了其互补性。结果表明,MALDI和ESI技术各有优劣,结合串联质谱分析,可获得糖肽的糖链结构信息;两条路线互补使用,在揭示蛋白质糖基化修饰(位点和结构)的研究中十分必要。     

Quantification and remote detection of nitro explosives by helium plasma ionization mass spectrometry (HePI‐MS) on a modified atmospheric pressure source designed for electrospray ionization

Helium Plasma Ionization (HePI) generates gaseous negative ions upon exposure of vapors emanating from organic nitro compounds. A simple adaptation converts any electrospray ionization source to a HePI source by passing helium through the sample delivery metal capillary held at a negative potential. Compared with the demands of other He‐requiring ambient pressure ionization sources, the consumption of helium by the HePI source is minimal (20–30 ml/min). Quantification experiments conducted by exposing solid deposits to a HePI source revealed that 1 ng of 2,4,6‐trinitrotoluene (TNT) on a filter paper (about 0.01 ng/mm²) could be detected by this method. When vapor emanating from a 1,3,5‐trinitroperhydro‐1,3,5‐triazine (RDX) sample was subjected to helium plasma ionization mass spectrometry (HePI‐MS), a peak was observed at m/z 268 for (RDX●NO₂)^?. This facile formation of NO₂^? adducts was noted without the need of any extra additives as dopants. Quantitative evaluations showed RDX detection by HePI‐MS to be linear over at least three orders of magnitude. TNT samples placed even 5 m away from the source were detected when the sample headspace vapor was swept by a stream of argon or nitrogen and delivered to the helium plasma ion source via a metal tube. Among the tubing materials investigated, stainless steel showed the best performance for sample delivery. A system with a copper tube, and air as the carrier gas, for example, failed to deliver any detectable amount of TNT to the source. In fact, passing over hot copper appears to be a practical way of removing TNT or other nitroaromatics from ambient air. Copyright © 2012 John Wiley & Sons, Ltd.     

Portable electrospray ionization mass spectrometry (ESI-MS) for analysis of contaminants in the field

Hitherto analysis of chemicals in the field using mass spectrometry (MS) has been limited to analysis of non-polar and thermally stabile organic compounds using either a direct gas leak or a membrane inlet as MS interface. Recently, Professor R. Graham Cooks’ group demonstrated that miniature mass spectrometers operating at elevated pressures (>0.13?Pa (1?·?10^?3??Torr)) can be combined with electrospray ionization (ESI) for analysis of polar as well as thermally labile organic compounds. We present a simple miniaturized ESI unit for analysis of small liquid samples using miniature mass spectrometry. The ESI unit operates without pumps and supplementary sheath gases, which makes it very simple to handle in the field. 20–30?µL of sample solution is simply dropped into a small cavity in the ESI unit, where after the spray is initiated by applying high voltage to it. The miniaturized ESI unit was tested in combination with a miniature mass spectrometer (the Mini 10 developed by Professor R. Graham Cooks, Purdue University, IN) and we found that common herbicides (Atrazine, Prometryne, Terbutryne and Triadimefone) could be detected with detection limits around 1?mg?L^?1 and with a quantitative reproducibility of +/?30%. These characteristics, although high for environmental samples, are comparable to detection limits obtained with other ESI units used with miniature mass spectrometers and represent an early step forward towards a future field instrument. A major advantage of the capillary spray cell is its direct compatibility with micro extraction techniques for sample pre-concentration.