Fragmentation of even electron ions: Protonated amines and esters

The fragmentation of protonated amines and esters is examined by collision induced dissociation of mass selected ions generated by chemical ionization. Four fragmentation types are observed: (i) loss of an alkane moiety, explicable in terms of a four-centered reaction, (ii) loss of alkene, also explicable as a four-centered process, (iii) loss of an alkyl radical, requiring electron unpairing, (iv) losses of other neutral molecules, viz. acids and alcohols from protonated esters, or amines and ammonia from protonated amines. Proposed mechanisms were checked by characterizing selected product ions through their collision induced dissociation spectra. The usefulness of these generalizations is substantiated by the successful prediction of the fragmentation patterns and the order of relative abundances of daughter ions for eight unknowns including some containing functional groups not studied previously.     

Intramolecular Electrophilic Aromatic Substitution in Gas-phase Fragmentation of Protonated N-Benzylbenzaldimines

In this study, the gas-phase fragmentations of protonated N-benzylbenzaldimines were investigated by electrospray ionization tandem mass spectrometry (ESI-MSⁿ). Upon collisional activation, several characteristic fragment ions are produced and their fragmentation mechanisms are rationalized by electrophilic aromatic substitution accompanied by benzyl cation transfer. (1) For N-(p-methoxybenzylidene)-1-phenylmethanimine, concomitant with a loss of HCN, a product ion at m/z 121 was observed. It is proposed to be generated from electrophilic substitution at the ipso-position by transferring benzyl cation rather than cleavage of the C-N double bond. (2) For N-(m-methoxybenzylidene)-1-phenylmethanimine, a product ion at m/z 209 was obtained, corresponding to the elimination of NH₃ carrying two hydrogens from the two aromatic rings respectively. This process can be rationalized by two sequential electrophilic substitutions and cyclodeamination reaction based on the benzyl cation transfer. Deuterium-labeled experiments, density functional theory (DFT) calculation and substituent effect results also corroborate the proposed mechanism. Figure a

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Fragmentation reactions of alkylphenylammonium ions

The fragmentation reactions of a variety of alkylphenylammonium ions, C(6)H(5)NH(3 -n)R(n)(+) (n >/= 1, R = CH(3), C(2)H(5), i-C(3)H(7), n-C(4)H(9)) were studied by energy-resolved mass spectrometry. Ionization was by fast atom bombardment (FAB) or electrospray ionization. Energy-resolved fragmentation data were obtained by low-energy collision-induced dissociation (CID) in the quadrupole cell of a hybrid sector/quadrupole instrument following FAB ionization and by cone-voltage CID in the interface region of the electrospray/quadrupole instrument. A comparison of the two methods of obtaining energy-resolved data showed that very similar results are obtained by the two methods. The fragmentation reactions of the alkylphenylammonium ions are rationalized in terms of competitive formation of an [R(+)-NC(6)H(5)H(3-n)R(n-1)] complex or a [C(6)H(5)H(3-n)R(n-1)N(+.)-(.)R] complex. The former complex fragments by internal proton transfer to yield C(6)H(5)H(3 -n)R(n -1)NH(+) and [R -H] whereas the latter complex fragments to form C(6)H(5)H(3 -n)R(n -1)N(+) and an alkyl radical. Alkane elimination, which is very prominent for tetraalkylammonium ions, most likely involves sequential elimination of an alkyl radical and either an H atom or an alkyl radical for the phenyl-substituted ammonium ions. Copyright 1999 John Wiley & Sons, Ltd.     

Fragmentation of amidinated peptide ions

The collision-induced dissociation characteristics of amidinated and unmodified tryptic peptides are compared using an ion trap mass spectrometer with both electrospray ionization and matrix-assisted laser/desorption ionization (MALDI). Several fragmentation pathways in a number of tryptic peptides of various precursor charge states are found to be enhanced. The additional information conveyed by the observed fragment ions should facilitate protein identifications.     

Fragmentation of negative ions from carbohydrates: Part 2. Fragmentation of high-mannose N-linked glycans

[M + NO3]- And [M + (NO3)2]2- ions were produced by electrospray from neutral high-mannose ([Man](5-9)[GlcNAc]2, [Glc](1-3)[Man](4-9)[GlcNAc]2) N-linked glycans and their 2-aminobenzamide derivatives sprayed from methanol:water containing ammonium nitrate. Low energy collision-induced decomposition (CID) spectra of both types of ions were almost identical and dominated by cross-ring and C-type fragments, unlike the corresponding spectra of the positive ions that contained mainly B- and Y-type glycosidic fragments. This behavior could be rationalized by an initial proton abstraction from various hydroxy groups by the initially-formed anionic adduct. These negative ion spectra were more informative than the corresponding positive ion spectra and contained prominent ions that were diagnostic of structural features such as the composition of individual antennas that were not easily obtainable by other means. C-ions defined the sequence of the constituent monosaccharide residues. Detailed fragmentation mechanisms are proposed to account for many of the diagnostic ions.     

Fragmentation of electrospray-produced oligodeoxynucleotide ions adducted to metal ions

In this article, we describe the unique fragmentations of oligodeoxynucleotides (ODNs) whose phosphate groups are completely depleted of protons and replaced with metal ions. The production of the ubiquitous [a(n) - base] ions still occurs, but no longer by transfer of an acidic phosphate proton to an adjoining 3' base. Nor is the extent of the reaction determined by the proton affinity of that base. Rather, the reaction now occurs via a cleavage 3' to both pyrimidines and purines; cleavage 3' to pyrimidine is more favorable than that 3' to purine. We also demonstrate that an ODN is more stable in the gas phase when its phosphate groups are bound to metal ions than when its phosphate groups are attached to hydrogens. This study also provides further evidence for the ODN fragmentation mechanism that involves H transfer to a nucleobase. To establish the structural utility of this new fragmentation, we applied it to distinguishing small ODNs containing a photomodified cis,syn-cyclobutane pyrimidine dimer from the parent ODNs, a system that cannot be distinguished by collisional activation of precursor species that do not contain metal ions.     

Fragmentation of negative ions from carbohydrates: Part 3. Fragmentation of hybrid and complex N-linked glycans

Hybrid and complex N-linked glycans were ionized by electrospray in the presence of ammonium nitrate to give [M + NO3]- and [M + (NO3)2]2- ions. Low energy collision-induced decomposition (CID) spectra of both types of ions were almost identical and were dominated by C-type glycosidic and cross-ring fragments, unlike the corresponding spectra of the positive ions that contained mainly B- and Y-type glycosidic fragments. Also, in contrast to fragments in the positive ion spectra, many of these ions appeared to be produced by single pathways following proton abstraction from specific hydroxy groups. Consequently, many ions were diagnostic for specific structural features. Such features included the composition of each of the two antennas, the presence or absence of a bisecting GlcNAc residue, and the location of fucose residues on the core GlcNAc residues and on the antennas. C-ions defined the sequence of the constituent monosaccharide residues. Detailed fragmentation mechanisms are proposed to account for several of the diagnostic ions.     

Reactions of TFDA with ketones. synthesis of difluoromethyl 2,2-difluorocyclopropyl ethers

The sequential reaction of 2 equiv of difluorocarbene (generated from trimethylsilyl fluorosulfonyldifluoroacetate (TFDA) by treatment with catalytic fluoride ion) with a series of electron-rich aromatic ketones and alpha,beta-unsaturated ketones leads to the formation of difluoromethyl 2,2-difluorocyclopropyl ethers in good yield.     

Fragmentation Reactions of Methionine-Containing Protonated Octapeptides and Fragment Ions Therefrom: An Energy-Resolved Study

The fragmentation reactions of the MH⁺ ions as well as the b₇, a₇, and a₇* ions derived therefrom have been studied in detail for the octapeptides MAAAAAAA, AAMAAAAA, AAAAMAAA, and AAAAAAMA. Ionization was by electrospray using a QqToF mass spectrometer, which allowed a study of the evolution of the fragmentation channels as a function of the collision energy. Not surprisingly, the product ion mass spectra for the b₇ ions are independent of the original precursor sequence, indicating macrocyclization and reopening to the same mixture of protonated oxazolones prior to fragmentation. The results show that this sequence scrambling results in a distinct preference to place the Met residue in the C-terminal position of the protonated oxazolones. The a₇ and a₇* ions also produce product ion mass spectra independent of the original peptide sequence. The results for the a₇ ions indicate that fragmentation occurs primarily from an amide structure analogous to that observed for a₄ ions (Bythell et al. in J Am Chem Soc 132:14766–14779, 2010). Clearly, the rearrangement reaction they have proposed applies equally well to a_n ions as large as a₇. The major fragmentation modes of the MH⁺ ions at low collision energies produce b₇, b_6, and b₅ ions. As the collision energy is increased further fragmentation of these primary products produces, in part, non-direct sequence ions, which become prominent at lower m/z values, particularly for the peptides with the Met residue near the N-terminus.

Fragmentation of organosulfur compounds upon electron impact. Part III. Metastable decomposition of the molecular ions of methyl thioglycolate and ethyl thioglycolate

The metastable decompositions of the molecular ions of methyl thioglycolate (1) and ethyl thioglycolate (2) were investigated by means of mass analyzed ion kinetic energy (MIKE) spectra and deuterium labeling. The loss of methanol is the only metastable decomposition of 1^+·. This fragmentation occurs via two distinct pathways. The molecular ions of 2 decompose in a variety of ways, i.e., the losses of water, ethene, ethanol or ?₂H₃O₂. All of these decompositions, except the loss of ethene, occur through two distinct mechanisms. During the loss of ?₂H₃O₂, the ethyl group or ethene migrates from the oxygen to the sulfur atom. The loss of H?S, which corresponds to the loss of H?O with a concomitant double hydrogen transfer observed in the case of methyl glycolate (3), does not participate in the metastable decomposition of 1^+· and 2^+·. This is due to the energetic favorableness of the loss of methanol.     

Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation

Peptoids are peptide-mimicking oligomers consisting of N-alkylated glycine units. The fragmentation patterns for six singly and doubly protonated model peptoids were studied via collision-induced dissociation tandem mass spectrometry. The experiments were carried out on a triple quadrupole mass spectrometer with an electrospray ionization source. Both singly and doubly protonated peptoids were found to fragment mainly at the backbone amide bonds to produce peptoid B-type N-terminal fragment ions and Y-type C-terminal fragment ions. However, the relative abundances of B- versus Y-ions were significantly different. The singly protonated peptoids fragmented by producing highly abundant Y-ions and lesser abundant B-ions. The Y-ion formation mechanism was studied through calculating the energetics of truncated peptoid fragment ions using density functional theory and by controlled experiments. The results indicated that Y-ions were likely formed by transferring a proton from the C–H bond of the N-terminal fragments to the secondary amine of the C-terminal fragments. This proton transfer is energetically favored, and is in accord with the observation of abundant Y-ions. The calculations also indicated that doubly protonated peptoids would fragment at an amide bond close to the N-terminus to yield a high abundance of low-mass B-ions and high-mass Y-ions. The results of this study provide further understanding of the mechanisms of peptoid fragmentation and, therefore, are a valuable guide for de novo sequencing of peptoid libraries synthesized via combinatorial chemistry.

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Direct synthesis of ethers from aldehydes and ketones. One-pot reductive etherification of benzaldehydes,alkyl aryl ketones,and benzophenones

Benzyl alcohols formed by the reduction of benzaldehydes, alkyl aryl ketones, and benzophenones with sodium tetrahydridoborate in alcohols undergo in situ etherification with the solvent in the presence of a catalytic amount of HCl. Thus the process may be regarded as one-pot transformation of carbonyl compounds into the corresponding benzyl ethers. The yields of ethers depend on the substituent nature in the aromatic fragment of the initial carbonyl compound and on the alcohol used as reduction medium.     

Free energies of electron ejection of aromatic hydrocarbon negative ions in ethers at room temperature

The free energies of electron ejection of some aromatic hydrocarbon mono- and di-negative ions in DME and 2-MTHF at room temperature are estimated from existing experimental data. The formation of free solvated electrons requires about the same amount of free energy whether the negative ion is present as a loosely bound or a tightly bound associate with the sodium counter ion. When the ejected electrons are trapped by a solvent cavity in the vicinity of the sodium ion the reaction requires appreciably less energy for the tightly bound than for the loosely bound associates. The data are essential for the study of the photo-ionization of aromatic hydrocarbon negative ions in ethers.     

Electron Capture Dissociation Studies of the Fragmentation Patterns of Doubly Protonated and Mixed Protonated-Sodiated Peptoids

The fragmentation patterns of a group of doubly protonated ([P + 2H]²⁺) and mixed protonated-sodiated ([P + H + Na]²⁺) peptide-mimicking oligomers, known as peptoids, have been studied using electron capturing dissociation (ECD) tandem mass spectrometry techniques. For all the peptoids studied, the primary backbone fragmentation occurred at the N-C_α bonds. The N-terminal fragment ions, the C-ions (protonated) and the C′-ions (sodiated) were observed universally for all the peptoids regardless of the types of charge carrier. The C-terminal ions varied depending on the type of charge carrier. The doubly protonated peptoids with at least one basic residue located at a position other than the N-terminus fragmented by producing the Z^?-series of ions. In addition, most doubly protonated peptoids also produced the Y-series of ions with notable abundances. The mixed protonated-sodiated peptoids fragmented by yielding the Z^?′-series of ions in addition to the C′-series. Chelation between the sodium cation and the amide groups of the peptoid chain might be an important factor that could stabilize both the N-terminal and the C-terminal fragment ions. Regardless of the types of the charge carrier, one notable fragmentation for all the peptoids was the elimination of a benzylic radical from the odd-electron positive ions of the protonated peptoids ([P + 2H]^?+) and the sodiated peptoids ([P + H + Na]^?+). The study showed potential utility of using the ECD technique for sequencing of peptoid libraries generated by combinatorial chemistry.

Fragmentation of homoallylic alkoxides. Synthesis of propenyl and 2-methylpropenyl ketones from carboxylic esters

An efficient two-step synthesis of propenyl and 2-methylpropenyl ketones from carboxylic esters is described which uses as the key step the fragmentation of a potassium dihomoallylic alkoxide under mild thermolytic conditions.     

Kinetic resolution of acyclic secondary allylic silyl ethers catalyzed by chiral ketones.

Kinetic resolution of acyclic secondary allylic silyl ethers by chiral dioxiranes generated in situ from chiral ketones (R)-1 and (R)-2 and Oxone was investigated. An efficient and catalytic method has been developed for kinetic resolution of those substrates with a CCl(3), tert-butyl, or CF(3) group at the alpha-position. In particular, high selectivities (S up to 100) were observed for kinetic resolutions of racemic alpha-trichloromethyl allylic silyl ethers 7 and 9-15 catalyzed by ketones (R)-2. Both the recovered substrates and the resulting epoxides were obtained in high enantiomeric excess. On the basis of steric and electrostatic interactions between the chiral dioxiranes and the racemic substrates, a model was proposed to rationalize the enantioselectivities and diastereoselectivities in the chiral ketone-catalyzed kinetic resolution process.