Fragmentation of β-hydroxy hydroperoxides

A β-hydroxy hydroperoxide was obtained through base-catalyzed disproportionation of a hydroperoxy endoperoxide available by singlet oxygenation of cyclohepta-1,4-diene. Vitamins E and C induce fragmentation of this β-hydroxy hydroperoxide generating aldehydes, especially in the presence of redox active metal ions such as those present in vivo, e.g., under conditions of "iron overload". This chemistry may contribute to the oxidative cleavage of polyunsaturated fatty acyls that produces similar aldehydes, which damage proteins and DNA through covalent adduction resulting in "oxidative injury".     

“Meta Elimination,” a Diagnostic Fragmentation in Mass Spectrometry

The diagnostic value of the “ortho effect” for unknown identification by mass spectrometry is well known. Here, we report the existence of a novel “meta effect,” which adds to the repertoire of useful mass spectrometric fragmentation mechanisms. For example, the meta-specific elimination pathway described in this report enables unequivocal identification of meta isomers from ortho and para isomers of carboxyanilides. The reaction follows a specific path to eliminate a molecule of meta-benzyne, from the anion produced after the initial decarboxylation of the precursor. Consequently, in the CID spectra of carboxyanilides, a peak for the (R-CO-NH)^– anion is observed only for the meta isomers. For example, the peaks observed at m/z 58, 86, 120, 128, and 170 from acetamido-, butamido-, benzamido, heptamido-, and decanamido-benzoates, respectively, were specific only to the spectra of meta isomers.     

Unusual Fragmentation of β-Linked Peptides by ExD Tandem Mass Spectrometry

Ion-electron reaction based fragmentation methods (ExD) in tandem mass spectrometry (MS), such as electron capture dissociation (ECD) and electron transfer dissociation (ETD) represent a powerful tool for biological analysis. ExD methods have been used to differentiate the presence of the isoaspartate (isoAsp) from the aspartate (Asp) in peptides and proteins. IsoAsp is a β₃-type amino acid that has an additional methylene group in the backbone, forming a C_α–C_β bond within the polypeptide chain. Cleavage of this bond provides specific fragments that allow differentiation of the isomers. The presence of a C_α–C_β bond within the backbone is unique to β-amino acids, suggesting a similar application of ExD toward the analysis of peptides containing other β-type amino acids. In the current study, ECD and ETD analysis of several β-amino acid containing peptides was performed. It was found that N–C_β and C_α–C_β bond cleavages were rare, providing few c and z type fragments, which was attributed to the instability of the C_β radical. Instead, the electron capture resulted primarily in the formation of a and y fragments, representing an alternative fragmentation pathway, likely initiated by the electron capture at a backbone amide nitrogen protonation site within the β amino acid residues.     

Reversible Addition–Fragmentation Chain‐Transfer Polymerization of Octadecyl Acrylate

Abstract

Polymerization of octadecyl acrylate (ODA) was carried out in benzene solution using the 2‐cyanoprop‐2‐yl dithiobenzoate (CPDB) as the reversible addition–fragmentation chain‐transfer (RAFT) agent and AIBN as the initiator. The results show the obtained polymer with controlled molecular weight and low PDI value. The relationships between both of the ln([M ₀]/[M]) vs. reaction time and molecular weight vs. conversion showed a straight line. The block copolymer of ODA and styrene (PODA‐b‐PSt) obtained using poly(octadecyl acrylate) (PODA) as a macro‐RAFT agent. The polymers were characterized by ¹H NMR, DSC, and gel permeation chromatograph (GPC). The effect of molar ratio [CPDB]:[AIBN] and reaction temperature on polymerization was investigated.     

New Fragmentation Pathways for Cephalosporins by Electrospray Ionization Quadrupole Time-of-flight Mass Spectrometry

Introduction Cephalosporins are antibiotics of β-lactam family. They have a broad spectrum of antibiotic activity due to their ability to inhibit bacterial cell wall synthesis of different Gram-positive and Gram-negative bacteria. Cephalosporins are used orally or parenterally to treat a wide variety of infections throughout the body and are often prescribed to fight penicillin resistant microorganisms.     

Negative Ion CID Fragmentation of <Emphasis Type="Italic">O-</Emphasis>linked Oligosaccharide Aldoses—Charge Induced and Charge Remote Fragmentation

Collision induced dissociation (CID) fragmentation was compared between reducing and reduced sulfated, sialylated, and neutral O-linked oligosaccharides. It was found that fragmentation of the [M – H]^– ions of aldoses with acidic residues gave unique Z-fragmentation of the reducing end GalNAc containing the acidic C-6 branch, where the entire C-3 branch was lost. This fragmentation pathway, which is not seen in the alditols, showed that the process involved charge remote fragmentation catalyzed by a reducing end acidic anomeric proton. With structures containing sialic acid on both the C-3 and C-6 branch, the [M – H]^– ions were dominated by the loss of sialic acid. This fragmentation pathway was also pronounced in the [M – 2H]^2– ions revealing both the C-6 Z-fragment plus its complementary C-3 C-fragment in addition to glycosidic and cross ring fragmentation. This generation of the Z/C-fragment pairs from GalNAc showed that the charges were not participating in their generation. Fragmentation of neutral aldoses showed pronounced Z-fragmentation believed to be generated by proton migration from the C-6 branch to the negatively charged GalNAc residue followed by charge remote fragmentation similar to the acidic oligosaccharides. In addition, A-type fragments generated by charge induced fragmentation of neutral oligosaccharides were observed when the charge migrated from C-1 of the GalNAc to the GlcNAc residue followed by rearrangement to accommodate the ^0,2A-fragmentation. LC-MS also showed that O-linked aldoses existed as interchangeable α/β pyranose anomers, in addition to a third isomer (25% of the total free aldose) believed to be the furanose form.     

Fragmentation Mechanism of Trans—α—Aryl—β—enamino Esters

Electron impact-induced fragmentation mechanism of Trans-α-Aryl-β-enamino esters were investigated using mass-analyzed ion kinetic energy (MIKE) spectrometry and high resolution accurate mass data It was found that the main characteristic fragmentations of compounds studied were:an odd electron ion M^ -EtOH was formed by losing a neutral molecule of ethanol;and the skeletal rearrangements took place;and the ring opening reaction happened after losing a carbon monoxide;and the typical McLafferty rearrangement underwent in ester group.The cycliztion reation caused by losing neutral molecule of TsNH2 due to the ortho-effects of substituted group of gromatic ring was also observed.     

More Than Charged Base Loss — Revisiting the Fragmentation of Highly Charged Oligonucleotides

Tandem mass spectrometry is a well-established analytical tool for rapid and reliable characterization of oligonucleotides (ONs) and their gas-phase dissociation channels. The fragmentation mechanisms of native and modified nucleic acids upon different mass spectrometric activation techniques have been studied extensively, resulting in a comprehensive catalogue of backbone fragments. In this study, the fragmentation behavior of highly charged oligodeoxynucleotides (ODNs) comprising up to 15 nucleobases was investigated. It was found that ODNs exhibiting a charge level (ratio of the actual to the total possible charge) of 100% follow significantly altered dissociation pathways compared with low or medium charge levels if a terminal pyrimidine base (3' or 5') is present. The corresponding product ion spectra gave evidence for the extensive loss of a cyanate anion (NCO^–), which frequently coincided with the abstraction of water from the 3'- and 5'-end in the presence of a 3'- and 5'-terminal pyrimidine nucleobase, respectively. Subsequent fragmentation of the M-NCO^– ion by MS³ revealed a so far unreported consecutive excision of a metaphosphate (PO₃ ^–)-ion for the investigated sequences. Introduction of a phosphorothioate group allowed pinpointing of PO₃ ^– loss to the ultimate phosphate group. Several dissociation mechanisms for the release of NCO^– and a metaphosphate ion were proposed and the validity of each mechanism was evaluated by the analysis of backbone- or sugar-modified ONs.

Redox Chemistry of Heterobimetallic Polypnictogen Triple-Decker Complexes – Rearrangement,Fragmentation and Transfer

The redox chemistry of the heterobimetallic triple-decker complexes [(Cp*Fe)(Cp′′′Co)(μ,η⁵:η⁴-E₅)] (E=P ( 1 ), As ( 2 ), Cp*=1,2,3,4,5-pentamethyl-cyclopentadienyl, Cp′′′=1,2,4-tri-tertbutyl-cyclopentadienyl) and [(Cp′′′Co)(Cp′′′Ni)(μ,η³:η³-E₃)] (E=P ( 10 ), As ( 11 )) was investigated. Compound 1 and 2 could be oxidized to the monocations 3 and 4 and further to the dications 5 and 6 , while the initially folded cyclo-E₅ ligand planarizes upon oxidation. The reduction leads to an opposite change in the geometry of the middle deck, which is now folded stronger into the direction of the other metal fragment (formation of monoanions 7 and 8 ). For the arsenic compound 8 , a different behavior is found since a fragmentation into an As₆ ( 9 ) and As₃ ligand complex occurs. The Co and Ni triple-decker complexes 10 and 11 can be oxidized initially to the heterometallic monocations 12 and 13 , which are not stable in solution and convert selectively into the homometallic nickel complexes 14 and 15 and the cobalt complexes 16 and 17 . This behavior was further proven by the oxidation of [(Cp′′′Co)(Cp′′Ni)(μ,η³:η²-P₃)] ( 19 , Cp′′=1,3-di-tertbutyl-cyclopentadienyl) comprising two different Cp ligands. The transfer of {Cp^RM} fragments can be suppressed when a {W(CO)₅} unit is coordinated to the P₃ ligand ( 20 ) prior to the oxidation and the mixed cobalt and nickel cation 21 can be isolated. The reduction of 10 and 11 yields the heterometallic monoanions 22 and 23 , where no transfer of the {Cp^RM} fragments is observed.     

Unusual Fragmentation of Peptide and Protein in Matrix-assisted Laser Desorption/lonization Mass Spectrometry

Unusual amine - bond fragmentation on the peptide/protein backbone has been reported using matrix - assisted laser desorption/ionization time - of- flight mass spectrometry (MALDI - TOFMS)The amine - bond cleavage occurred without metastable decay, while the peptide - bond cleavage occurred with metastable decay of peptide ions in a drift region of TOF mass analyzer. It was presumed that the amine - bond cleavage occurred as a non - ergodic process independent of the ionization under MALDI conditions.     

Fragmentation Behavior and Ionization Potentials of Aluminum Clusters Al_n(n≤40)

Al2-Al40 clusters were studied by means of the all-electron DFT method.The properties of the aluminum clusters including binding energy,the second difference in energy,HOMO-LUMO gap,especially fragmentation energies and ionization potentials,were analyzed.The main products from the dissociations of aluminum cluster ions are shown to be Al+Al+n-1 for the larger clusters,and Al++Aln-1 for the smaller ones.And,the calculated ionization potentials are consistent with the experiment data.     

Fragmentation of alkoxy radicals: Mechanistic aspects of the tandemβ-fragmentation-intramolecular functionalization reaction

The formation of the β-peroxylactone (4) during the photolysis of lactol (3) with (diacetoxyiodo)-benzene (DIB) and iodine under oxygen atmosphere demostrates the presence of a peroxyradical intermediate in the tandem β-fragmentation-intramolecular functionalization reaction.     

Fragmentation Behavior and Ionization Potentials of Lead Clusters Pb_n(n≤30)

The properties of Pbn(n=2―30) clusters including binding energies,second differences in energy,and HOMO-LUMO gaps,especially fragmentation energies and ionization potentials,have been studied by ab initio calculation.The main fragmentation products of Pbn+ are shown to be Pb+Pbn-1+ for n≤14 and two small cluster fragments for larger ones with n14.The Pb13+ appears frequently as the products in the fragmentations of large clusters.Also,the calculated ionization potentials of the clusters are consistent with the experiment data.     

Fragmentation processes in phthalimide- and pyridine-2,3-dicarboimidoalkyl-α-diazoketones under resonant electron capture

Resonant electron capture (REC) mass spectra of phthalimide- and pyridine-2,3-dicarboimidoalkyl-α-diazoketones have been investigated. Based on calculations using the Hartree–Fock method and density functional theory with the B3LYP functional the structure of the negative ions (NIs) [M–N₂]^? and [M–N₂–C₃H₃RO]^? as well as the reactions leading to their formation have been proposed.     

Computational study of Rh(I)-Catalyzed Cycloaddition–Fragmentation of N-cyclopropylacrylamides

Rh-catalyzed cycloaddition–fragmentation of N-cyclopropylacrylamides is an effective method to directly obtain substituted azocanes. In this transformation, the challenging step is insertion of CO and alkene into the more hindered proximal cyclopropane CC bond while avoiding competitive less hindered proximal CC activation. Given the importance of this novel strategy, we performed a density functional theory study to clarify the catalytic mechanism. The calculations confirm that cleavage of the more hindered bond is more favorable than cleavage of the less hindered bond for Rh-catalyzed (7 + 1) cycloaddition of N-cyclopropylacrylamides. Comparison between Rh-catalyzed (3 + 1 + 2) and (7 + 1) cycloaddition shows that the coordination mode with different ligand plays a crucial role in enabling different CC cleavage. The main factors responsible for the occurrence of β-hydride elimination rather than CC reductive elimination are also discussed. The kinetic preference for β-hydride elimination can be attributed to the transition state of CC reductive elimination being more distorted and forming in a much more concerted fashion than that of β-hydride elimination. Additionally, C4H elimination is disfavored owing to weaker interaction energy compared with C7H elimination by analyzing using the distortion/interaction model.     

Fragmentation Chemistry of [Met-Gly]•+, [Gly-Met]•+, and [Met-Met]•+ Radical Cations

Radical cations [Met-Gly]^?+, [Gly-Met]^?+, and [Met-Met]^?+ have been generated through collision-induced dissociation (CID) of [Cu^II(CH₃CN)₂(peptide)]^?2+ complexes. Their fragmentation patterns and dissociation mechanisms have been studied both experimentally and theoretically using density functional theory at the UB3LYP/6-311++G(d,p) level. The captodative structure, in which the radical is located at the α-carbon of the N-terminal residue and the proton is on the amide oxygen, is the lowest energy structure on each potential energy surface. The canonical structure, with the charge and spin both located on the sulfur, and the distonic ion with the proton on the terminal amino group, and the radical on the α-carbon of the C-terminal residue have similar energies. Interconversion between the canonical structures and the captodative isomers is facile and occurs prior to fragmentation. However, isomerization to produce the distonic structure is energetically less favorable and cannot compete with dissociation except in the case of [Gly-Met]^?+. Charge-driven dissociations result in formation of [b _n – H]^?+ and a ₁ ions. Radical-driven dissociation leads to the loss of the side chain of methionine as CH₃-S-CH?=?CH₂ producing α-glycyl radicals from both [Gly-Met]^?+ and [Met-Met]^?+. For [Met-Met]^?+, loss of the side chain occurs at the C-terminal as shown by both labeling experiments and computations. The product, the distonic ion of [Met-Gly]^?+, NH₃ ⁺CH(CH₂CH₂SCH₃)CONHCH^?COOH dissociates by loss of CH₃S^?. The isomeric distonic ion NH₃ ⁺CH₂CONHC^?(CH₂CH₂SCH₃)COOH is accessible directly from the canonical [Gly-Met]^?+ ion. A fragmentation pathway that characterizes this ion (and the distonic ion of [Met-Met]^?+) is homolytic fission of the C_β–C_γ bond to lose CH₃SCH₂ ^?.      

Biocatalytic Steroidal 9α-Hydroxylation and Fragmentation Enable the Concise Chemoenzymatic Synthesis of 9,10-Secosteroids

9,10-Secosteroids are an important group of marine steroids with diverse biological activities. Herein, we report a chemoenzymatic strategy for the concise, modular, and scalable synthesis of ten naturally occurring 9,10-secosteroids from readily available steroids in three to eight steps. The key feature lies in utilizing a Rieske oxygenase-like 3-ketosteroid 9α-hydroxylase (KSH) as the biocatalyst to achieve efficient C9−C10 bond cleavage and A-ring aromatization of tetracyclic steroids through 9α-hydroxylation and fragmentation. With synthesized 9,10-secosteroides, structure–activity relationship was evaluated based on bioassays in terms of previously unexplored anti-infective activity. This study provides experimental evidence to support the hypothesis that the biosynthetic pathway through which 9,10-secosteroids are formed in nature shares a similar 9α-hydroxylation and fragmentation cascade. In addition to the development of a biomimetic approach for 9,10-secosteroid synthesis, this study highlights the great potential of chemoenzymatic strategies in chemical synthesis.     

Effect of intramolecular dynamics on state-to-state photochemistry: Fragmentation of the à state of trans-DONO

The effect of intramolecular dynamics on state-selected photolysis of trans-DONO is probed through measurements on the OD fragment ejected by the à state with one and two quanta of energy in the -NO stretching vibration ν₂. The fragment in the latter case is rotationally hotter, more polarized at high rotational energies, and is associated with a higher population non-equilibrium in the Λ-doublet fine-structure states. These effects are traced back to coupling between the ν₂ vibration and the in-plane DON angle-bending motion ν₃ in the parent molecule.     

Fragmentation energetics of the phenol(+)···Ar(3) cation cluster

The various dissociation thresholds of phenol(+)···Ar(3) complexes for the consecutive loss of all three Ar ligands were measured in a molecular beam using resonant photoionization efficiency and mass analyzed threshold ionization spectroscopy via excitation of the first excited singlet state (S(1)). The adiabatic ionization energy is derived as 68077 ± 15 cm(-1). The analysis of the dissociation thresholds demonstrate that all three Ar ligands in the neutral phenol···Ar(3) tetramer are attached to the aromatic ring via π-bonding, denoted phenol···Ar(3)(3π). The value of the dissociation threshold for the loss of one Ar ligand from phenol(+)···Ar(3)(3π), ～190 cm(-1), is significantly lower than the binding energy measured for the π-bonded Ar ligand in the phenol(+)···Ar(π) dimer, D(0) = 535 ± 3 cm(-1). This difference is rationalized by an ionization-induced π → H isomerization process occurring prior to dissociation, that is, one Ar atom in phenol(+)···Ar(3)(3π) moves to the OH binding site, leading to a structure with one H-bonded and 2 π-bonded ligands, denoted phenol(+)···Ar(3)(H/2π). The dissociation thresholds for the loss of two and three Ar atoms are also reported as 860 and 1730 cm(-1). From these values, the binding energy of the H-bound Ar atom can be estimated as 870 cm(-1).     

Fragmentation behavior of Si2Cln+ cations (n = 1—6)

Sector-field mass spectrometry was used to probe the fragmentation patterns of the cationic silicon chlorides Si₂Cl_n ⁺ (n = 1—6). For almost all Si₂Cl_n ⁺ ions, Si—Si fragmentation predominates the Si—Cl bond cleavage both in the metastable ion and collisional activation mass spectra. Analysis of the fragmentation patterns indicates that the long-lived radical cation Si₂Cl₆ ^·+ corresponds to a complex [SiCl₂·SiCl₄]^·+ rather than the intact molecular ion of hexachlorodisilane. The behavior of Si₂Cl₅ ⁺ is consistent with the formation of the (trichlorosilyl)dichlorosilyl cation Cl₃SiSICl₂ ⁺. Structural aspects are also discussed for the other Si₂Cl_n ⁺ species. A semi-quantitative analysis of the fragmentation patterns in conjunction with the literature thermochemistry data was used to estimate some thermochemical properties of the Si₂Cl_n ⁺ cations.