Identification of position isomers by energy‐resolved mass spectrometry

This study reports an energy‐resolved mass spectrometric (ERMS) strategy for the characterization of position isomers derived from the reaction of hydroxyl radicals (^●OH) with diphenhydramine (DPH) that are usually hard to differentiate by other methods. The isomer analogues formed by ^●OH attack on the side chain of DPH are identified with the help of a specific fragment ion peak (m/z 88) in the collision‐induced dissociation (CID) spectrum of the protonated molecule. In the negative ion mode, the breakdown curves of the deprotonated molecules show an order of stability (supported by density functional theory (DFT) calculations) ortho > meta > para of the positional isomers formed by the hydroxylation of the aromatic ring. The gas phase stability of the deprotonated molecules [M ? H]^? towards the benzylic cleavage depends mainly on the formation of intramolecular hydrogen bonds and of the mesomeric effect of the phenol hydroxyl. The [M ? H]^? molecules of ortho and meta isomers result a peak at m/z 183 with notably different intensities because of the presence/absence of an intramolecular hydrogen bonding between the OH group and C9 protons. The ERMS approach discussed in this report might be an effective replacement for the conventional methods that requires very costly and time‐consuming separation/purification methods along with the use of multi‐spectroscopic methods. Copyright © 2015 John Wiley & Sons, Ltd.     

Anomeric information obtained from a series of synthetic trisaccharides using energy resolved mass spectra

The majority of structural investigations of oligosaccharides based on mass spectrometry use naturally occurring oligosaccharides, which do not allow extracting any common feature associated with anomeric structures and linkage positions. In order to address the issue to find such characteristics possibly contained in oligosaccharide structure, a synthetic combinatorial trisaccharide library was analyzed. The trisaccharides used in the analysis consisted of L-fucose, D-galactose and D-glucose, in which individual glycosidic linkages existed in either alpha- or beta-anomers. The analysis of energy-resolved mass spectra (ERMS) and the scattered plot analysis of some parameters obtained from ERMS for a series of trisaccharides revealed that lower activation energy was required for the dissociation of alpha-glycosides of these sugars compared to those of the corresponding beta-anomers. It is suggested that this finding may be useful in structural analysis of natural oligosaccharides.     

Peak width‐mass correlation in CID MS/MS of isomeric oligosaccharides using traveling‐wave ion mobility mass spectrometry

Isomeric oligosaccharides γ‐cyclodextrin (γ‐CD), glucosyl‐βCD (Glc₁‐βCD) and maltosyl‐αCD (Glc₂‐αCD) were analyzed by traveling‐wave ion mobility (twIM) mass spectrometry (MS). Their formation of multicharged multimers differed from each other. The ion mobility‐mass spectrometry was useful in the self‐assembling and complex formation analyses of CD isomers. The drift times of the isomers and their product ions with the same mass were almost the same in collision‐induced dissociation (CID) MS/MS. In contrast, the ion mobility peak widths were sensitive to structural differences of the isomeric product ions. The twIM peak width (ms ‐ µs) of the product ions [M ? Glc_n + H]⁺ (n = 0 ～ 6) of γ‐CD correlated linearly with their masses (Da); the large and/or long chain product ions had wider peak widths, which were much wider than those from the general diffusion effect. This was a novel and useful ‘trend line’ to discriminate between the three isomers. Plots of [M ? Glc_{2 ～ 6} + H]⁺ of Glc₁‐βCD and [M ? Glc_{3 ～ 6} + H]⁺ of Glc₂‐αCD product ions' plots were on the same trend line as γ‐CD. The plots of [M ? Glc₁ + H]⁺ of Glc₁‐βCD and [M ? Glc_{1, 2} + H]⁺ of Glc₂‐αCD strayed from the γ‐CD line; their peak widths were narrower than those of γ‐CD. These results indicated that product ions from the chemical species of Glc₁‐β CD and Glc₂‐αCD retained their CD structure. Analyses of the IM peak widths enable us to elucidate the structures of the product ions. Copyright © 2009 John Wiley & Sons, Ltd.     

Identification of isomeric 5‐hydroxytryptophan‐ and oxindolylalanine‐containing peptides by mass spectrometry

Cells continuously produce reactive oxidative species that can modify all cellular components. In proteins, for example, cysteine, methionine, tryptophan (Trp), and tyrosine residues are particularly prone to oxidation. Here, we report two new approaches to distinguish two isomeric oxidation products of Trp residues, i.e. 5‐hydroxytryptophan (5‐HTP) and oxindolylalanine (Oia) residues, in peptides. First, 2‐nitrobenzenesulfenyl chloride, known to derivatize Trp residues in position 2 of the indole ring, was used to label 5‐HTP residues. The mass shift of 152.98 m/z units allowed identifying 5‐HTP‐ besides Trp‐containing peptides by mass spectrometry, whereas Oia residues were not labeled. Second, fragmentation of the Oia‐ and 5‐HTP‐derived immonium ions at m/z 175.08 produced ions characteristic for each residue that allowed their identification even in the presence of y₁ ions at m/z 175.12 derived from peptides with C‐terminal arginine residues. The pseudo MS³ spectra acquired on a quadrupole time‐of‐flight hybrid mass spectrometer displayed two signals at m/z 130.05 and m/z 132.05 characteristic for Oia‐containing peptides and a group of six signals (m/z 103.04, 120.04, 130.04, 133.03, 146.04, and 148.04) for 5‐HTP‐cointaining peptides. In both cases, the relative signal intensities appeared to be independent of the sequence providing a specific fingerprint of each oxidative modification. Copyright © 2012 John Wiley & Sons, Ltd.     

Time‐of‐flight mass spectrometry for time‐resolved measurements: Some developments and applications

In this paper, the time resolution for kinetic studies of reactions with mass spectrometric detection is characterized in detail, and it is shown how this allows faster kinetic processes to be determined. The time‐resolved technique used pulsed laser photolysis to initiate reaction and a time‐of‐flight mass spectrometer (TOFMS) to monitor progress, where the reactant gas was sampled by a sampling orifice and photoionized using pulsed, laser vacuum ultraviolet light before being analyzed by the TOFMS. Characterization of this setup has been carried out to identify the parameters that affect the time for “sampling,” which limits the fastest reactions that can be measured. A simple mathematical equation has been developed to correct for “sampling” delays (k_sampling～25, 000 s^?1), which extends the range of rate coefficients to be measured in a kinetic mass spectrometry reactor to k′ < 7000 s^?1. This method could be applied to any other kinetic mass spectrometry system where k_sampling can be measured; an important advantage since it allows the study of reactions over a wider range of conditions (e.g., larger concentrations of reagents/products can be used to minimize the contribution from wall losses). The system can produce reliable kinetic data whether monitoring reactant decay or product growth even when the reaction and sampling processes are occurring on a similar timescale (k′ < 7000 s^?1). Reproducible and reliable kinetic data have been obtained for the following reactions: SO + NO₂ → products (R1), ClSO + NO₂ → products (R2), where SO and ClSO were monitored under pseudo‐first‐order conditions, and HCO + O₂ → CO + HO₂ (R3), where CO was monitored by a [1+1] resonance enhanced ionization multiphoton ionization (REMPI) scheme with HCO reacting under pseudo–first‐order conditions. The limitations and potential developments of this setup are described. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 44: 532–545, 2012     

Arrival time distributions of product ions reveal isomeric ratio of deprotonated molecules in ion mobility–mass spectrometry of hyaluronan‐derived oligosaccharides

Hyaluronic acid is a naturally occurring linear polysaccharide with substantial medical potential. In this work, discrimination of tyramine‐based hyaluronan derivatives was accessed by ion mobility–mass spectrometry of deprotonated molecules and nuclear magnetic resonance spectroscopy. As the product ion mass spectra did not allow for direct isomer discrimination in mixture, the reductive labeling of oligosaccharides as well as stable isotope labeling was performed. The ion mobility separation of parent ions together with the characteristic fragmentation for reduced isomers providing unique product ions allowed us to identify isomers present in a mixture and determine their mutual isomeric ratio. The determination used simple recalculation of arrival time distribution areas of unique ions to areas of deprotonated molecules. Mass spectrometry data were confirmed by nuclear magnetic resonance spectroscopy. Copyright © 2015 John Wiley & Sons, Ltd.     

Gas‐phase dissociation of ionic liquid aggregates studied by electrospray ionisation mass spectrometry and energy‐variable collision induced dissociation

Positive singly charged ionic liquid aggregates [(C_nmim)_m+1(BF₄)_m]⁺ (mim = 3‐methylimidazolium; n = 2, 4, 8 and 10) and [(C₄mim)_m+1(A)_m]⁺ (A = Cl⁻, BF₄⁻, PF₆⁻, CF₃SO₃⁻ and (CF₃SO₂)₂N⁻) were investigated by electrospray ionisation mass spectrometry and energy‐variable collision induced dissociation. The electrospray ionisation mass spectra (ESI‐MS) showed the formation of an aggregate with extra stability for m = 4 for all the ionic liquids with the exception of [C₄mim][CF₃SO₃]. ESI‐MS‐MS and breakdown curves of aggregate ions showed that their dissociation occurred by loss of neutral species ([C_nmim][A])_a with a ≥ 1. Variable‐energy collision induced dissociation of each aggregate from m = 1 to m = 8 for all the ionic liquids studied enabled the determination of E_{cm, 1/2} values, whose variation with m showed that the monomers were always kinetically much more stable than the larger aggregates, independently of the nature of cation and anion. The centre‐of‐mass energy values correlate well with literature data on ionic volumes and interaction and hydrogen bond energies. Copyright © 2008 John Wiley & Sons, Ltd.     

Ion trap MS using high trapping gas pressure enables unequivocal structural analysis of three isobaric compounds in a mixture by using energy‐resolved mass spectrometry and the survival yield technique

Recently, it has been shown that energy‐resolved mass spectrometry (MS) can provide quantitative information from two isomeric or isobaric compounds in mixtures by using the survival yield (SY) technique together with “gas‐phase collisional purification” (GPCP) strategy (Anal. Chem., 2016, 88, p.10821). Herein, we present an improvement and an extension of this concept to the structural analysis of a model mixture of three isobaric compounds (two peptides and a polyether). By using default collision‐induced dissociation (CID) tandem MS parameters on an ion trap instrument, the previous approach did not show any signs of isobaric contamination. However, by modifying CID conditions and using a threefold increase of the He trapping gas pressure (to reach 3.00·10^?5 mbar), the SY curve was unexpectedly and strongly shifted to higher excitation voltages with two plateaus appearing. Those plateaus, indicating clearly the presence of three isobaric compounds, were taken as reliable indicators to perform GPCP at carefully selected excitation voltages in order to selectively fragment one compound after the other. In this way, CID mass spectra of each compound were correctly recovered, both in terms of fragment ion peaks and in terms of relative intensities, from energy‐resolved MSⁿ spectra of the three compounds mixture. This feature enables their unequivocal structural analysis as if samples were free from isobaric interferences. In this paper, we also discuss the possibility for recovering SY curves for pure compounds directly from the mixture. Clearly, in this case, the higher He trapping gas pressure made it possible to use the SY technique, for the first time, for the structural analysis in the case of mixtures of three isobaric compounds. This observation, quite unexpected, demonstrates that the trapping gas pressure is of paramount importance although it is usually not considered in energy‐resolved MS for structural and/or quantitative analysis.     

How does the molecular velocity distribution affect kinetics measurements by time‐resolved mass spectrometry?

The equations governing the time fidelity in molecular‐beam mass sampling are derived for supersonic‐beam sampling, where the velocity distribution is well‐fitted by a displaced Maxwell–Boltzmann distribution. Supersonic sampling is shown to offer much higher fidelity than the corresponding effusive‐beam sampling, and rules of thumb are derived for the validity of kinetic measurements for supersonic‐beam sampling. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 565–570, 2007     

T‐Jump/time‐of‐flight mass spectrometry for time‐resolved analysis of energetic materials

We describe a new T‐Jump/time‐of‐flight (TOF) mass spectrometer for the time‐resolved analysis of rapid pyrolysis chemistry of solids and liquids, with a focus on energetic materials. The instrument employs a thin wire substrate which can be coated with the material of interest, and can be rapidly heated (10⁵ K/s). The T‐Jump probe is inserted within the extraction region of a linear TOF mass spectrometer, which enables multiple spectra to be obtained during a single reaction event. By monitoring the electrical characteristics of the heated wire, the temperature could also be obtained and correlated to the mass spectra. As examples, we present time‐resolved spectra for the ignition of nitrocellulose and RDX. The fidelity of the instrument is demonstrated in the spectra presented which show the temporal formation and decay of several species in both systems. The simultaneous measurement of temperature enables us to extract the ignition temperature and the characteristic reaction time. The time‐resolved mass spectra obtained show that these solid energetic material reactions, under a rapid heating rate, can occur on a time scale of milliseconds or less. While the data sampling rate of 10 000 Hz was used in the present experiments, the instrument is capable of a maximum scanning rate of up to ～30 kHz. The capability of high‐speed time‐resolved measurements offers an additional analytical tool for the characterization of the decomposition, ignition, and combustion of energetic materials. Copyright © 2008 John Wiley & Sons, Ltd.     

Recognition and resolution of isomeric alkyl anilines by mass spectrometry

Two MS techniques have been used to recognize and resolve a representative isomeric pair of N-alkyl and ring-alkyl substituted anilines. The first technique (1) uses MS/MS to perform ion/molecule reactions of structurally-diagnostic fragment ions (SDFI) whereas the second (2) uses traveling wave ion mobility spectrometry (TWIMS) of the pair of protonated molecules followed by on-line collision-induced dissociation (CID), that is, MS/TWIMS-CID/MS. Isomeric C₇H₇N⁺ ions of m/z 106 (1′ from 4-butylaniline and 2 from N-butylaniline) are formed as abundant fragments by 70 eV EI of the anilines, and found to function as suitable SDFI. Ions 1′ and 2 display nearly identical unimolecular dissociation chemistry, but contrasting bimolecular reactivity with ethyl vinyl ether, isoprene, acrolein, and 2-methyl-1,3-dioxolane. Ion 2 forms adducts to a large extent whereas 1′ is nearly inert towards all reactants tested. The intact protonated anilines are readily resolved and recognized by MS/TWIMS-CID/MS in a SYNAPT mass spectrometer (Waters Corporation, Manchester, UK). The protonated N-butyl aniline (the more compact isomer) displays shorter drift time and higher lability towards CID than its 4-butyl isomer. The general application of SDFI 1′ and 2 and other homologous and analogous ions and MS/TWIMS-CID/MS for absolute recognition and resolution of isomeric families of N-alkyl and ring-alkyl mono-substituted anilines and analogues is discussed.