Fragmentation pathways arising from protonation at different sites in aminoalkyl‐substituted 3‐hydroxy‐1,2,5‐oxadiazoles (3‐hydroxyfurazans)

Grossert, J. Stuart; Boschi, Donatella; Lolli, Marco Lucio; White, Robert L.

doi:10.1002/rcm.8166

Cited by 4 publications

(22 citation statements)

References 49 publications

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“…In this cyclization process, a formal positive charge develops on N5 of the furazan ring and its fragmentation is analogous to the initial process characterized previously for 1a and 2a when protonated on N5. 37 The present and previous 37 computations indicated that the energy of the ion formed by protonation of the heterocyclic alkyl amine varied with protonation site, conformation, the extent of hydrogen bonding, and the tautomeric form of the heterocycle. The similar energetics provided several possibilities as starting points for fragmentation pathways and indicated that structural isomers of isobaric ions are generated during electrospray ionization.…”

Section: Discussionmentioning

confidence: 58%

“…Overall, the relative energies of the ions were equivalent to those computed for the shorter chain protonated ω-aminoalkyl-3-hydroxyfurazans (1a and 2a). 37 Note that protonation of the primary amino group created structural connections matching the structure of ammonia. 37 The loss of ammonia from the terminal position of an aliphatic chain has been documented for several protonated, structural analogs, such as diaminoalkanes, 42 diamino, dicarboxylic acids, 38,42 aminoalcohols, 43 muscimol, an aminomethyl substituted hydroxyisoxazole, [44][45][46] and amlodipine, an aminoethoxymethyl substituted dihydropyridine calcium channel blocker.…”

Section: Protonation Site and Initial Neutral Loss Of Ammoniamentioning

confidence: 99%

“…37 Note that protonation of the primary amino group created structural connections matching the structure of ammonia. 37 The loss of ammonia from the terminal position of an aliphatic chain has been documented for several protonated, structural analogs, such as diaminoalkanes, 42 diamino, dicarboxylic acids, 38,42 aminoalcohols, 43 muscimol, an aminomethyl substituted hydroxyisoxazole, [44][45][46] and amlodipine, an aminoethoxymethyl substituted dihydropyridine calcium channel blocker. 47,48 In particular, the structures of both tautomers of the 3-hydroxyfurazans 3a and 4a closely resemble the structures of the monoprotonated forms of the common, naturally occurring diamino acids ornithine (OrnH + ) and lysine (LysH + ) (Figure 3).…”

Section: Protonation Site and Initial Neutral Loss Of Ammoniamentioning

confidence: 99%

“…34 The aminomethyl-and 2-aminoethyl 3-hydroxyfurazans 1 and 2 were readily protonated by electrospray ionization mass spectrometry (ESI MS, positive mode) and fragmented by ring cleavage upon collision-induced dissociation (CID). 37 In the lowest energy pathway, ring cleavage was accompanied by neutral losses of nitric oxide (NO) and carbon monoxide (CO). At higher collision energies, other fragmentation pathways, including an initial loss of ammonia, were observed as well.…”

Section: Introductionmentioning

confidence: 99%

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Intramolecular interactions and the neutral loss of ammonia from collisionally activated, protonated ω-aminoalkyl-3-hydroxyfurazans

Grossert,

Boschi,

Lolli

et al. 2023

Eur J Mass Spectrom (Chichester)

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Gas phase fragmentation reactions of monoprotonated 4-(3-aminopropyl)- and 4-(4-aminobutyl)-3-hydroxyfurazan were investigated to examine potential interactions between functional groups. The two heterocyclic alkyl amines were ionized by electrospray ionization (ESI, positive mode) and fragmented using tandem mass spectrometry (MS/MS). The fragmentation pathways were characterized using pseudo MS3 experiments, precursor-ion scans, and density functional computations. For both heterocyclic ions, loss of ammonia was the only fragmentation process observed at low collision energies. Computational analysis indicated that the most feasible mechanism was intramolecular nucleophilic displacement of ammonia from the protonated ω-aminoalkyl side chain by N5 of the furazan ring. The alkylated nitrogen in the resulting bicyclic product ion facilitated N-O bond cleavage; subsequent neutral losses of nitric oxide (NO) and carbon monoxide (CO) occurred by homolytic bond cleavages. Next in the multistep sequence, neutral loss of ethylene from a radical cation was observed. A less favorable, competing fragmentation pathway of protonated 4-(3-aminopropyl)-3-hydroxyfurazan was consistent with cleavage of the 3-hydroxyfurazan ring and losses of NO and CO. Overall, the similar fragmentation behavior found for protonated 4-(3-aminopropyl)- and 4-(4-aminobutyl)-3-hydroxyfurazan differed from that previously characterized for furazan analogs with shorter alkyl chains. These observations demonstrate that a small change in the structure of multifunctional, heterocyclic alkyl amines may significantly influence interactions between distinct functional groups and the nature of the fragmentation process.

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Section: Discussionmentioning

confidence: 58%

Section: Protonation Site and Initial Neutral Loss Of Ammoniamentioning

confidence: 99%

Section: Protonation Site and Initial Neutral Loss Of Ammoniamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intramolecular interactions and the neutral loss of ammonia from collisionally activated, protonated ω-aminoalkyl-3-hydroxyfurazans

Grossert,

Boschi,

Lolli

et al. 2023

Eur J Mass Spectrom (Chichester)

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“…Protonation of the more basic side‐chain amino group generates structural connections that closely resemble the structure of ammonia 54 . The intramolecular displacement of NH 3 by the nucleophilic α‐nitrogen, 7,8,11,28 as well as hydroxyl 29,30,42 and carboxyl 11,29 groups in bifunctional alkanes, is precedented in several previous mass spectral studies.…”

Section: Resultsmentioning

confidence: 91%

Fragmentation reactions of protonated α,ω‐diamino carboxylic acids: The importance of functional group interactions

Grossert

White

2021

J Mass Spectrom

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Protonated members of a homologous series of biologically significant α,ω‐diamino carboxylic acids were subjected to collision induced dissociation (CID). The resulting fragmentation patterns were studied using isotopic labeling, quantum mechanical computations, and pseudo MS3 experiments conducted primarily on an ion trap mass spectrometer. Each protonated α,ω‐diamino acid showed a primary neutral loss of either ammonia or water; a clear explanation was developed for the observed variation of the two losses within the series. Protonated 2,3‐diaminopropanoic acid, 2,4‐diaminobutanoic acid, and 2,7‐diaminoheptanoic acid gave secondary losses of water, carbon monoxide, and a loss of water plus carbon monoxide, respectively. In the parallel pathways characterized for the fragmentations of protonated ornithine and lysine, the α‐nitrogen of the diamino acid was maintained in the cyclic iminium product formed by successive losses of NH3 and (H2O + CO), whereas the side‐chain nitrogen was retained by consecutive losses of H2O and (CO, NH3). The 1‐piperideine ion from protonated lysine was fragmented further, losing ethylene from carbons 4 and 5. Protonated 2,6‐diaminopimelic acid fragmented by analogous reactions. Detailed mechanistic schemes for the fragmentation of both protonated 2,3‐diaminopropanoic and ornithine were generated from MP2/DFT computations. This work highlights the participation of the side‐chain amino group, which distinguishes the gas‐phase chemistry of protonated α,ω‐diamino acids from the well‐documented fragmentation reactions of protonated α‐amino acids bearing a hydrogen atom or an alkyl side chain. In general, the results further illustrate the importance of intramolecular separations affecting the specific interactions between functional groups leading to the fragmentation of multifunctional ions.

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Tandem mass spectrometry of homologous 3‐hydroxyfurazan and nitrile amino acids: Analysis of cooperative interactions and fragmentation processes

Grossert,

Crowell,

Boschi

et al. 2024

J Mass Spectrom

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The assignment of structure by tandem mass spectrometry (MS/MS) relies on the interpretation of the fragmentation behavior of gas‐phase ions. Mass spectra were acquired for a series of heterocyclic mimetics of acidic amino acids and a related series of nitrile amino acids. All amino acids were readily protonated or deprotonated by electrospray ionization (ESI), and distinctive fragmentation processes were observed when the ions were subjected to collision‐induced dissociation (CID). The deprotonated heterocycles showed bond cleavages of the 3‐hydroxyfurazan ring with formation of oxoisocyanate and the complementary deprotonated nitrile amino acid. Further fragmentation of the deprotonated nitrile amino acids was greatly dependent on the length of the alkyl nitrile side chain. Competing losses of CO2 versus HCN occurred from α‐cyanoglycinate (shortest chain), whereas water was lost from 2‐amino‐5‐cyanopentanoate (longest chain). Interestingly, loss of acrylonitrile by a McLafferty‐type fragmentation process was detected for 2‐amino‐4‐cyanobutanoate, and several competing processes were observed for β‐cyanoalanate. In one process, cyanide ion was formed either by consecutive losses of ammonia, carbon dioxide, and acetylene or by a one‐step decarboxylative elimination. In another, complementary ions were obtained from β‐cyanoalanate by loss of acetonitrile or HN=CHCO2H. Fragmentation of the protonated 3‐hydroxyfurazan and nitrile amino acids resulted in the cumulative loss (H2O + CO), a loss that is commonly observed for protonated aliphatic α‐amino acids. Overall, the distinct fragmentation behavior of the multifunctional 3‐hydroxyfurazan amino acids correlated with the charged site, whereas fragmentations of the deprotonated nitrile amino acids showed cooperative interactions between the nitrile and the carboxylate groups.

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Fragmentation pathways arising from protonation at different sites in aminoalkyl‐substituted 3‐hydroxy‐1,2,5‐oxadiazoles (3‐hydroxyfurazans)

Abstract: The product ions obtained by the competing fragmentation processes varied with the site of protonation. Interestingly, the most abundant product ions observed at low collision energies were formed by cleavage of protonated molecules possessing more internal energy than other isomers.

Cited by 4 publications

References 49 publications

Intramolecular interactions and the neutral loss of ammonia from collisionally activated, protonated ω-aminoalkyl-3-hydroxyfurazans

Intramolecular interactions and the neutral loss of ammonia from collisionally activated, protonated ω-aminoalkyl-3-hydroxyfurazans

Fragmentation reactions of protonated α,ω‐diamino carboxylic acids: The importance of functional group interactions

Tandem mass spectrometry of homologous 3‐hydroxyfurazan and nitrile amino acids: Analysis of cooperative interactions and fragmentation processes

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