Low-energy collision-induced fragmentation of negative ions derived from diesters of aliphatic dicarboxylic acids made with hydroxybenzoic acids

Diesters of ortho-hydroxybenzoic acid (salicylic acid) made with glutaric, adipic, and pimelic acids are the monomers of some potential drug candidates for aspirin patches. Collision-induced dissociation (CID) spectra of negative ion derived from these compounds show a 120-Da 'neutral loss' specific to the ortho isomers. In contrast, the anions derived from diesters of meta- and para-hydroxybenzoic acids show a 138-Da loss for an elimination of elements of hydroxybenzoic acid by a charge-remote mechanism. Deuterium labeling studies confirmed that the hydrogen atom transferred for hydroxybenzoic acid loss originates specifically from the alpha position of the dicarboxylic acid moiety. Although all spectra showed a peak at m/z 137, a charge-mediated process specific for the ortho compounds renders it the most prominent peak in the spectra of ortho compounds. Appropriate deuterium labeling experiments demonstrated that the hydrogen atom transferred for the formation of the m/z 137 ion in ortho compounds is specifically derived from the alpha position of the dicarboxylic acid moiety.     

Competing gas-phase fragmentation pathways of asparagine-, glutamine-, and lysine-containing protonated dipeptides

The fragmentation chemistry of protonated H–Val–Asn–OH, H–Val–Gln–OH and H–Val–Lys–OH is investigated in this work by means of modeling and density functional theory calculations. Former experimental studies indicate that the ratio of a ₁ and y ₁ ions cannot be explained by considering the proton affinities of the corresponding dissociating species on the a ₁–y ₁ pathway, while the fragmentation of other dipeptides can be understood in this way. We demonstrate that considering the correct PA value for H–Asn–OH eliminates the deviation observed for H–Val–Asn–OH. The larger than expected a ₁/y ₁ ratio of H–Val–Gln–OH is explained by considering the dissociation kinetics of the proton-bound dimers formed on the a ₁–y ₁ pathway and competition of the deamidation and a ₁–y ₁ channels. For H–Val–Lys–OH, it is proposed that a ₁ ions are indeed formed from one of the primary products, protonated H–Val–Cap–OH.     

Reaction competition in the fragmentation of protonated dipeptides

A major low-energy fragmentation reaction of many protonated dipeptides involves cleavage of the amide bond resulting in formation of either the y(1)" ion or the a(1) ion. For a series of protonated dipeptides H-Val-Xxx-OH it is observed that log(y(1)"/a(1)) is a linear function of the proton affinity of the variable C-terminal amino acid. For the series of protonated dipeptides H-Xxx-Phe-OH log(a(1)/y(1)") gives a poor correlation with the proton affinity or gas-phase basicity of H-Xxx-OH. However, a good limited correlation of log(a(1)/y(1)") with the Taft-Topsom sigma(alpha) for the alkyl group is observed when Xxx is an aliphatic amino acid. It is proposed that fragmentation occurs by initial formation of a proton-bound complex of an aziridinone and an amino acid which may fragment to form either a protonated amino acid (y(1)") or an N-protonated aziridinone with the corresponding neutrals being an aziridinone and an amino acid. Ab initio calculations show that the N-protonated aziridinone is unstable and fragments by loss of CO to form the a(1) immonium ion. However, the proton-bound complex of an aziridinone and an amine base is a stable species which exists in a potential well. Copyright 2000 John Wiley & Sons, Ltd.     

Mass spectra of negative ions of aliphatic ω-oxocarboxylic acid derivatives

Conclusions Fragmentation of the molecules of methyl esters of aliphatic -oxocarboxylic acids upon dissociative capture of electrons includes processes of fragmentation that are characteristic for each functional group individually. It has been established that terminal functional groups separated by a saturated chain of four carbon atoms will interact, thus demonstrating that this molecule can exist in the folded conformation.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2238–2246, October, 1984.     

Towards A qualitative rationalisation of the fragmentation reactions of organic negative molecular ions

A set of axioms is formulated which provides a means for the qualitative rationalization and prediction of the fragmentation modes of organic molecular anions.     

Investigations of the fragmentation pathways of benzylpyridinium ions under ESI/MS conditions

Benzylpyridinium ions are often used as ‘thermometer ions’ in order to evaluate the internal energy distribution of the ions formed in sources of mass spectrometers. However, the detailed fragmentation pathways of these parent ions were not well established. In particular, fragmentation involving a rearrangement (RR) process may be influencing the simulated distribution curves. In a previous study, we suggested that such RR actually occurred under electrospray ionization/mass spectrometry (ESI/MS) and fast atom bombardment/mass spectrometry (FAB/MS) experiments. Here, we present a systematic study of different substituted benzylpyridinium ions. Theoretical calculations showed that RR fragmentation leading to substituted tropylium ions could occur under ‘soft ionization’ conditions, such as ESI or FAB. Experimental results obtained under gas‐phase reactivity conditions showed that some substituted benzylpiridinium compounds actually undergo RR fragmentations under ESI/MS conditions. Mass‐analyzed kinetic experiments were also carried out to gain information on the reaction pathways that actually occur, and these experimental results are in agreement with the reaction pathways theoretically proposed. Copyright © 2009 John Wiley & Sons, Ltd.     

Separation of amino alcohols using divalent dipeptides as counter ions in aqueous CE

Divalent dipeptides have been introduced as counter ions in aqueous CZE. The dipeptides form ion pairs with amino alcohols in the BGE and facilitate the separation of amino alcohols. High concentrations of dipeptide caused reversed effective mobility for the analytes. The net charge of the dipeptide can be controlled using a buffer or a strong base, and regulates the interaction between the dipeptide and the amino alcohol. A stronger interaction and higher selectivity of amino alcohols was observed when the dipeptides were used as divalent counter ions, than in monovalent or uncharged form. Association constants for ion pairs between divalent dipeptides and amino alcohols can be used to enhance selectivity for amino alcohols in CZE. No chiral separation of amino alcohols was observed when using the dipeptides as ion‐pairing chiral selectors in aqueous BGE, but addition of methanol to the BGE promoted enantioselectivity.     

Isomerization and fragmentation of aliphatic ether radical cations: Interconversion of distonic ions and cyclopropane intermediates

The reactions of propyl ether radical cations close to threshold are initiated by (reversible) formation of γ-disitonic isomers, R$ \mathop {\rm O}\limits^ + $ (H)CH₂CH₂CH₂^·. The three methylene groups in these ions lose their positional identity by ring closure/ring opening via [cyclopropane + alcohol]^+· intermediates. Extensive hydrogen exchange occurs within the C₃-chain. When R is not methyl the γ-distonic isomer undergoes further intramolecular hydrogen atom transfer reactions that lead to formation of α- and β-distonic ions. The α-distonic isomers expel ethyl and propyl radicals by C? O bond cleavage.     

Collision-induced fragmentation of negative ions from N-linked glycans derivatized with 2-aminobenzoic acid

N-Linked glycans from bovine ribonuclease B, chicken ovalbumin, bovine fetuin, porcine thyroglobulin and human alpha(1)-acid glycoprotein were derivatized with 2-aminobenzoic acid by reductive amination and their tandem mass spectra were recorded by negative ion electrospray ionization with a quadrupole time-of-flight mass spectrometer. Derivatives were also prepared from 2-amino-5-methyl- and 2-amino-4,5-dimethoxybenzoic acid in order to confirm the identity of fragment ions containing the reducing terminus. Major fragments from the [M - H](-) ions from the neutral glycans retained the derivative (Y-type cleavages) and provided information on sequence and branching. Other major fragments were products of A-type cross-ring cleavages giving information on antenna structure. Singly doubly and triply charged ions were formed from sialylated glycans. They produced major fragments by loss of sialic acid and a series of singly charged ions that were similar to those from the neutral analogues. Doubly charge ions were also produced by the neutral glycans and were fragmented to form product ions with one and two charges. Again, the fragment ions with a single charge were similar to those from the singly charged parents, but branching information was less obvious because of the occurrence of more abundant ions produced by multiple cleavages. Detection limits were around 200 fmol (3 : 1 signal-to-noise ratio).     

Study of the major fragmentation pathways of cypermethrin and related synthetic insecticides using tandem mass spectrometry

Fragmentation pathways of the synthetic pyrethroid cypermethrin and four structurally related insecticides were investigated using a tandem quadrupole mass spectrometer incorporating a hexapole collision cell under positive-ion electron impact ionization conditions. Conventional mass spectrometry using the first quadrupole analyser only and tandem mass spectrometry on selected precursor ions and product ions, and also constant neutral loss scan experiments, were used. Mechanisms and fragmentation pathways are proposed to explain the inherent stability of ions associated with the benzylphenoxy portion of this class of insecticide.     

Two-component density functional theory of positron binding to negative ions

The problem of binding in positron-negative ion systems has been addressed via two-component density functional theory. Calculations have been performed within the local density approximation for electron exchange-correlation as well as for the electron-positron correlation potential using a self-interaction corrected version of the density functional equations. Our results indicate that a positron forms a stable bound state with the negative ions Li⁻,B⁻,C⁻,O⁻,F⁻ and Cl⁻ with respect to dissociation into a negative ion and a positron or a neutral atom and positronium. Inclusion of electron-positron correlation deepens the positron bound state and stabilizes the system compared to earlier exchange-only calculations.     

The mechanism of formation and specifics of fragmentation for negative molecular ions of allylsilanes

The processes of formation of negative ions by allylsilane molecules were studied by resonanceelectron-capture mass spectrometry, and photoelectron spectra of these compounds were obtained. It was experimentally found that the overwhelming majority of fragment negative ions are produced in the energy range ～6–10 eV. It was shown that the resonance-electron-capture mass spectrum is almost entirely described by one or two series of intershell resonances due to excitation of an electron successively from several higher occupied orbitals to the lower unoccupied π molecular orbital.     

Dissociative double electron capture,dynamics of fragmentation of the water and hydrogen sulfide negative ions

The technique of ion kinetic energy spectrometry has been used to observe the unimolecular decompositions of H₂O^?? and H₂S^?? generated by charge exchange of the corresponding high velocity positive ions. The method involves dissociative double electron capture by a high velocity ion and allows the study of unstable negative ions that may be directly observable by conventional electron capture techniques. Information on the energetics of the reaction is obtained from the kinetic energy of the product ion. The reactions under consideration are shown in (1) and (2) where X = O or S.

The kinetic energy releases accompanying the reactions given in (1) and (2) have been measured and compared to those for the collision-induced reactions which produce the corresponding positive ions. The results have been used to deduce that the sequence of steps in the formation of the fragment negative ions is that given in (1) and (2). The cross section of OH^? formation is observed to be somewhat greater than for O^? production. This result is in contrast with dissociative electron capture cross sections from the neutral species and is interpreted on the basis of the energetic requirements for the reactions under consideration. H₂O^? reacts from different electronic states in yielding OH^? on the one hand and O^? on the other. The energy partitioning associated with reaction (2) suggests that the neutral productions 2H' rather than H₂. The kinetic energy losses accompanying excitation and kinetic energy releases upon fragmentation were similar for the corresponding reactions of the sulfur and oxygen-containing ions indicating related mechanisms in the two sets of reactions.     

In-Electrospray source Hydrogen/Deuterium exchange coupled to multistage fragmentation for the investigation of the protonation and fragmentation pathways of gas phase ions

Identification of molecules in complex natural matrices relies on matching the fragmentation spectra of ions under investigation and the spectra acquired for the corresponding analytical standards. Currently, there are many databases of experimentally measured tandem mass spectrometry spectra (such as NIST, MzCloud, and Metlin), and considerable progress has been made in the development of software for predicting tandem mass spectrometry fragments in silico using combinatorial, machine learning, and quantum chemistry approaches (such as MetFrag, CFM-ID, and QCxMS). However, the electrospray ionization molecules can be ionized at different sites (protonated or deprotonated), and the fragmentation spectra of such ions are different. Here, we are using the combination of the in-ESI source hydrogen/deuterium exchange reaction and MSⁿ fragmentation for the investigation of the fragmentation pathways for different protomers of organic molecules. It is shown that the distribution of the deuterium in the fragment ions reflects the presence of different protomers. For several molecules, the distribution of deuterium was traced up to the MS⁵ level of fragmentation revealing many unusual and unexpected effects. For example, we investigated the loss of HF from the ciprofloxacin and norfloxacin ions and observed that for ions protonated at –COOH group, the eliminating hydrogen always comes from –NH group. When ions are protonated at another site, the elimination of hydrogen with a probability of 30% occurs from the –NH group, and with a probability of 70%, it originates from other sites on the molecule. Such effects were not described previously. Quantum chemical simulation was used for the verification of the protonated structures and simulation of the corresponding fragmentation spectra.     

Mass spectrometric fragmentation of n-alkanes: Self-consistency test of a statistical theory

The fragmentation patterns of n-paraffins in the C₁₀–C₃₀ range are accounted for using a statistical, maximal entropy, formalism. The theory can be used in a predictive manner. Particular attention is given here to a quantitative test of the theory which is independent of the uncertainties in the structure of the fragments.