Simple Cleavage Research Articles

Characterizing the electrospray ionization mass spectral fragmentation pattern of indole derivatives synthesized from 2‐keto glycosides

Four indole derivatives synthesized from 2-keto glycosides were analyzed by electrospray ionization tandem mass spectrometry (ESI-MSn) with low-energy collision-induced dissociation to establish a general structural elucidation of indole derivatives. Their fragmentation pathways are proposed on the basis of the MSn studies and deuterium-labeled experiments. Indole derivatives undergo complicated gas-phase rearrangements in addition to simple bond cleavages. A rearrangement, which involves a contraction of the six-membered ring, was observed and a mechanism was proposed. The observations may have some potential applications in the interpretation of the mass spectra of indole derivatives.

Fragmentation of tryptophan by low-energy electrons

Decomposition of gas phase tryptophan (trp) following low energy (<10 eV) electron attachment is investigated by means of a crossed electron/molecular beam experiment. Various negatively charged species are observed, attributed to (trp − H) − (203 amu), (gly-yl) − (74 amu), HCO 2 - (45 amu), CN − (26 amu), OH − (17 amu), and O - / NH 2 - (16 amu). These fragments arise from either simple bond cleavages (e.g., (trp − H) −) or more complex reaction involving molecular rearrangements within the transitory negative ion (e.g., (HCO 2) −). Surprisingly, by far the most predominant dissociation processes occur at sub-excitation energies (below the threshold of the electronic excitation). The present Letter may contribute to a better understanding of the initial molecular processes taking place during the interaction of radiation with living systems.

The Formation and Heats of Formation of Simple α-Distonic Ions

Several methods for the preparation of α-distonic radical cations by unimolecular fragmentation in the gas phase have been examined, but generally applicable and satisfactory methods were not found. One commonly encountered problem is the contamination of the product ion beam by isotopic contributions from ions whose nominal mass is one unit lower (often formed by simple cleavage of the precursor ion). A novel α-distonic ion, (CH3)2NHCH2+•, was discovered and characterized. Composite ab initio methods of the G3 and CBS families were used to determine the heats of formation of the molecular ions and the α-distonic isomers of simple alcohols, ethers and amines with up to four carbon atoms. The α-distonic isomers are the lower energy species only for ionized alcohols and primary amines.

Proximity effects in the electron impact mass spectra of 2-substituted benzazoles

The 70eV electron impact mass spectra of a wide range of 2-substituted benzazoles are reported and discussed. Particular attention is paid to the mechanistic significance and analytical utility of [M–H]+ and [M–X]+ signals in the spectra of benzazoles in which the 2-substituent contains a terminal aryl group with one or more substituents, X. Loss of H or X occurs preferentially from an ortho-position from ionized 2-benzylbenzimidazoles, 2-phenethylbenzimidazoles, 2-styrylbenzimidazoles, 2-styrylbenzoxazoles and 2-styrylbenzothiazoles. In the three styrylbenzazole series, the [M–H]+ and/or [M–X]+ signals dominate the spectra. This unusually facile loss of H or X may be attributed to a proximity effect, in which cyclization of the ionized molecule is followed by elimination of an ortho-substituent to give an exceptionally stable polycyclic ion. Formation of a new five- or six-membered ring by the proximity effect occurs rapidly; cyclization to a seven-membered ring takes place rather less readily; but formation of a ring with only four atoms or more than seven atoms is not observed to a significant extent. The proximity effect competes effectively with loss of a methyl radical by simple cleavage of an ethyl, isopropyl and even a t-butyl group in the pendant aromatic ring of ionized 2-(4-alkylstyryl)benzazoles.

Simple and Efficient Cleavage Reaction of the Boc Group in Heterocyclic Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Photoionization of 2,3-dimethyl-2-butanol (thexyl alcohol): interaction between the charged and expelled fragments

Photoionization studies of (CH 3) 2CHC(CH 3) 2OH ( tert-hexyl alcohol, also called thexyl alcohol) exhibit four fragmentations below 10 eV. As with other tertiary alcohols, no molecular ion is detected. The only ion observed at threshold corresponds to propane loss. Examination of a deuterated analogue, (CH 3) 2CHC(CD 3) 2OH, shows only loss of C 3H 7D, implying that the fragment ion has the structure of ionized acetone enol. There is no evidence for reversible deuterium transposition, as has been reported for isotopomers of the homologous secondary alcohol (CH 3) 2CHCH(CH 3)OH. Propane loss from thexyl alcohol is attributed to intermediacy of ion–neutral complexes containing isopropyl radical and O-protonated acetone. Simple cleavage to give O-protonated acetone has an appearance energy 18 kJ mol −1 higher than that of propane loss. Thermochemical estimates and ab initio calculations both predict that methyl loss should have a lower threshold than the fragmentation leading to isopropyl loss, but experiments show the appearance energy to be 6 kJ mol −1 higher. This is consistent with previous reports of reverse activation barriers for methyl cleavages. Finally, formation of tert-hexyl cation, (CH 3) 2CHC(CH 3) 2 +, is observed with an appearance energy comparable to that of methyl loss, substantially below that predicted for OH radical expulsion from the molecular ion. The comparatively low threshold of this fragmentation is ascribed to ion-pair formation (concomitant with hydroxide ion) directly from an electronically excited neutral. Interactions between charged and neutral fragments (including energetics, bond orders <1, and electrical charges on molecular fragments) are explored using a combination of DFT and ab initio methods, along with topological analysis using the Atoms in Molecules approach.

Hydrogen radical abstraction by small ionized molecules, distonic ions and ionized carbenes in the gas phase

In the gas phase and within ion–neutral complexes, H abstraction by the ion from the neutral moiety was studied by using FT-ICR experiments and molecular orbital calculations. Ionized methanol abstracts rapidly H from methane and other alkanes while its α-distonic counterpart, CH 2OH 2 +, is completely unreactive. On the other hand, β-distonic ions, such as CH 2CH 2XH + (X=OCH 3, NH 2), are also unreactive towards methane but can abstract H from ketones and ethers. Finally, ionized carbenes, such as HOCNH 2 +, react with methane by a slow H abstraction. Ab initio molecular orbital calculations at the G3(MP2) level were performed in order to understand these behaviors. For ionized methanol and its α-distonic counterpart, the reacting structure that could lead to H abstraction is the highly stabilized complex between protonated methanol and a methyl radical, which yields the final state (CH 3OH 2 ++ CH 3) by simple cleavage. In the case of methanol the encounter complex with methane leads easily by rotation of the methane molecule to this reacting structure. In contrast, in the case of the α-distonic ion, the almost linear structure of the encounter complex [ CH 2OH 2 +⋯CH 4] and the high energy required for its isomerization into the reacting structure prevent the reaction. Two factors are required to observe H abstraction in β-distonic ions: the interaction energy of the encounter complex and the distance between the hydrogen to be transferred and the carbon radical. Reaction of the HOCNH 2 + carbene with methane lies between these two extreme cases. The encounter complex is poorly stabilized (−8.7 kcal mol −1) and the transition state for H abstraction is very close to the reactants energy.

Effect of thickness and PEG addition on the hydrolytic degradation of PLLA

We previously demonstrated that cylindrical, biodegradable reservoirs fabricated with polylactide-polyethylene glycol (PLLA : PEG) films maintain constant permeability and enable zeroorder drug delivery for up to 6 weeks in vitro. This research proposes that PEG not only enhances permeability but also extends of life of the device by allowing the escape of soluble degraded monomers thereby minimizing autocatalysis of PLLA. To test this hypothesis, cylindrical PLLA films with varying PEG concentrations (0–30%, w/w) and film-thickness (0.05–0.18 mm) were fabricated, and their degradation rate and thermal properties monitored for 23 weeks in vitro. The decrease in PLLA molecular weight for all films followed bi-exponential kinetics that fit the equation:yt = M(e–K1t + e– K2t ), as was determined by a Pearson's coefficient > 0.95 for all films. The constant M was empirically determined to be equal to have the initial molecular weight of the degrading polymer. The value of K 1 was 5–60 orders of magnitude greater than K 2 and was attributed to the autocatalytic degradation based on its dependence on PEG concentration, film thickness, and correlation with the enthalpy change associated with the glass transition (ΔC p). K 2 was attributed to simple hydrolytic cleavage of PLLA. The decrease in the value of K 1 with PEG concentration and thickness, and the correlation of K 1 with ΔC p, confirmed that the PLLA degradation can be controlled by incorporating PEG, as well as by modifying thickness.

Simple and efficient cleavage reaction of the boc group in heterocyclic compounds

AbstractDedicated to the memory of Pr. Ladjama Daif A series of chiral cyclosulfamides have been synthesized by alkaline cyclisation starting from N‐benzoylamino acids (Ala, Val, Leu, Phe) derivatives and chlorosulfonyl isocyanate. A simplified and regioselective deprotection of the cyclic compounds (cyclosulfamides) containing the tert‐butyloxycarbonyl group (Boc) has been achieved in good yield by fusion under reduced pressure.

Determination of kinetic parameters for hammerhead and hairpin ribozymes.

The application of conventional enzymological methods to the study of hairpin and hammerhead ribozymes has led to valuable insights into the mechanisms by which these small RNAs catalyze phosphodiester cleavage and ligation reactions. Here, protocols are presented for measuring rate constants for simple cleavage and ligation reactions mediated by minimal hammerhead and hairpin ribozymes under standard experimental conditions. Information is also provided to help researchers recognize and interpret more complex reaction kinetics that can be observed for ribozyme-sequence variants under a variety of reaction conditions.

A Simple Synthesis of Pyridine Aminophosphinic Acids and Pyridine Aminophosphine Oxides. The Unusual Cleavage of Pyridylmethyl-( N -benzylamino)-phenylphosphinic Acids and Phosphine Oxides in Acidic Solutions

Pyridine aminophosphinic acids were synthesized in reaction of N-(benzyl)-pyridylmethylimines with ethyl phenylphosphinate, in the presence of bromotrimethylsilane. Pyridine aminophosphine oxides were obtained in excellent yields by treatment of the corresponding imines with diphenylphosphine oxide. Among these compounds, the 2-pyridyl and 4-pyridyl derivatives were subject to a simple cleavage in aqueous mineral acid solutions. Products of the cleavages were N-(pyridylmethyl)benzylamines and phenylphosphonic (or diphenylphosphinic) acid, respectively.

Reactions of CH(3)CHO(.+) and of CH(3)COH(.+) with water upon Fourier transform ion cyclotron resonance conditions.

The reactions of CH(3)CHO(+) and of CH(3)COH(+) with water yield the same products, at almost the same rate. It is shown, by using a characteristic reaction of the carbene structure, that a molecule of water converts CH(3)COH(+) into its more stable isomer CH(3)CHO(+), which is a new example of catalyzed 1,2-H transfer. The dominant product is the proton-bound dimer of water which, in fact, comes from the [H(2)OH(+)...CH(3)(.)] and [H(2)OH(+)...CO] primary products whose observed abundances are poor. In a related system, ionized formamide/water, a water molecule catalyzes the 1,3-transfer leading from the solvated carbene to the [H(2)O...H(+)...H(2)N-C=O)] stable intermediate, which eliminates CO without back energy. In contrast, such a process does not take place in the studied system since the cleavage of the so formed [H(2)OH(+)...CH(3)CO] transient intermediate involves a high back energy; this is explained by the charge repartition within this intermediate. In fact, a different pathway takes place. The solvated acetaldehyde ion isomerizes into a terbody intermediate in which protonated water is bonded to a CO molecule on the one hand and to a methyl radical on the other hand. Simple cleavages of this complex yield the observed products.

The role of hydride migration in the mechanism of alcohol elimination from protonated ethers upon chemical ionization: Experiment and theory

An enhanced elimination of methanol under isobutane-chemical ionization (CI) conditions, resulting in highly abundant [MHCH 3OH] + ions, has been observed in several primary and secondary methyl ethers having a tertiary β-position (methine), as compared with those with β-methylene. This elimination is stereospecific in stereoisomeric 2-methyl-1-methoxycyclohexanes and in other ethers affording significantly more abundant [MHCH 3OH] + ions in the cis-isomers than in their trans-counterparts. These findings suggest involvement of a 1,2-hydride migration from the β- to α-position in the course of the alcohol elimination from the MH + ions of the above cis-ethers, resulting in stabilized tertiary carbocation structures. The possible pathways of methanol elimination from protonated cis-2-methyl-1-methoxycyclohexane were explored by density functional calculations at the B3LYP/6-31+G(d,p) level of theory. The transition states for MeOH elimination involving 1,2-hydride migration were located and the activation energy of the process was evaluated. The activation barrier of the alcohol elimination assisted by 1,2-hydride migration is lower by ∼10 kcal/mol than the simple bond cleavage (9.6 kcal/mol vs. 20.5 kcal/mol). These computational results support the mechanistic pathway involving the 1,2-hydride transfer. A step-wise mechanistic pathway is proposed for the less efficient elimination of methanol from protonated trans-2-methyl-1-methoxycyclohexane.

Expression, purification and crystallization of the Plasmodium falciparum enoyl reductase.

New hope has been gained in the control of the malaria parasite Plasmodium falciparum (pf) with the discovery that the parasite contains a prokaryotic type II fatty-acid synthase (FAS). Since enzymes of this type are absent in humans, they are potential targets for the development of new drugs. The enoyl reductase enzyme (ENR) belonging to this pathway is of particular interest because it has been shown to be inhibited by submicromolar concentrations of the antimicrobial agent triclosan. Here, the development of an efficient overexpression system for pfENR as a fusion protein with maltose-binding protein, its simple one-step purification and cleavage from its fusion protein and crystallization under new conditions with bound NAD(+) cofactor and triclosan are reported. The crystals belong to the space group P2(1), with approximate unit-cell parameters a = 88.2, b = 82.4, c = 94.8 A, beta = 90.77 degrees, and contain a tetramer in the asymmetric unit. Cryocooled crystals (100 K) diffracted to beyond 2.2 A resolution at the Daresbury Synchrotron Radiation Source.

Electrospray ionization and liquid secondary ion mass spectrometric study of N-heterocyclic carbenes and their 1,2,4-triazolium salt precursors

N-Heterocyclic carbenes and their 1,2,4-triazolium salt precursors were analyzed by electrospray ionization (ESI) and liquid secondary ion mass spectrometry (LSIMS). It was found that under applied conditions the C5 carbene center is formed from [M+ClO 4] + ion, were M corresponds to the 1,2,4-triazolium dicationic system, by loss of HClO 4 molecule. Further decomposition of formed carbene ions, namely [M−H] + ion, consist in the breaking of triazolium ring and loss bulky substituents from N1 and N4 atoms through the hydrogen transfer to the carbene center. This is in contrast to the [M] 2+ carbene precursor ions for which only the loss of N1 substituent occurred as a simple heterolytic bond cleavage.

How does chlorine substitution on acetonitrile affect the internal S N2 isomerization of proton-bound pairs (ClCH 2CN)(ROH)H + (R=CH 3, C 2H 5, C 3H 7)?

The unimolecular reactions of proton-bound pairs of chloroacetonitrile and a variety of alcohols (methanol, ethanol, n- and i-propanol) were studied in order to probe the impact of chloro-substitution on both the internal S N2 rearrangement leading to dehydration and simple hydrogen-bond cleavage reactions. Chloro-substitution on acetonitrile does not significantly affect the height of the highest energy isomerization barrier which governs the dehydration reaction but does reduce the relative energy of the transition state that leads to the formation of the high energy intermediate ion (CH 3CH⋯R⋯OH 2) +. Kinetic modeling of the unimolecular reactions with RRKM theory showed that this latter reaction is a key step in governing the ratio of the two types of reactions observed in the MI mass spectra even though it is not the rate-limiting step for the overall isomerization mechanism leading to dehydration. Chloro-substitution also reduces the proton affinity of acetonitrile resulting in the lowest energy simple-bond cleavage reaction products to be ROH 2 ++ClCH 2CN in all cases.

Ambident reactivity and characterization of small ionized carbenes

The gas phase reactions of five ionized carbenes, HCOH + 1, HCNH 2 + 2, CH 3COH + 3, HOCOH + 4 and HOCNH 2 + 5 with different molecules are studied by FT-ICR mass spectrometry. Interaction between an ionized carbene and a molecule can yield two kinds of stable adducts, as expected from the electronic structure of the carbene radical cations, explaining the ambident reactivity of these ions. The first kind of adduct corresponds to H-bonded species (hydrogen-bridged radical cations), the second to covalent structures. Since interconversion between these adducts is generally slow, each kind of adduct leads to a particular set of reactions. The H-bonded species can be involved in the protonation of the neutral as well as in the catalyzed interconversion between the carbene and its conventional radical cation counterpart. The covalent adducts, formed by reaction of ionized carbenes with methanal and alkenes, are β-distonic ions. Reactions with labeled propene show that the so formed distonic ions either dissociate by simple cleavage or undergo rearrangements and H-exchange after isomerization into conventional ions by 1,4-H transfers. Cyclopropane gives a characteristic reaction of the carbene structure: addition yields a γ-distonic ion which loses ethylene. Finally, H , I and SCH 3 abstraction from appropriate neutrals confirms a radical reactivity of the carbenic carbon.

A new, simple, and selective palladium-catalyzed cleavage of triethylsilyl ethers.

[reaction: see text] A simple procedure for the cleavage of triethylsilyl (TES) ethers in the presence of 10 wt % Pd/C in methanol or 95% ethanol is reported. This method allows selective removal of alkyl TES ethers in the presence of aromatic TES ethers or tert-butyldimethylsilyl (TBS) protecting groups.

Free Radicals in Mass Spectrometry. Part I. General Fragmentation Rules for Organic and Organometallic Compounds under Electron Impact

General fragmentation rules for isomerization and fragmentation processes based on firm thermochemical grounds are presented for positive odd- and even-electron ions. The thermochemical approach by ions' and free radicals' heats of formation, appearance and critical energies allowed the unification of many known fragmentation and isomerization processes. It is shown that to describe more than 180 classes of organic and hetero-organic compounds it is sufficient to apply only 21 types of isomerization and fragmentation processes. Most of these types are characterized with a specific mechanism and the stabilization morde for ions and/or neutral species. Many original fragmentation schemes are given. In addition to simple bond cleavages, it was demonstrated that the quasi-equilibrium theory of Eyring et al. Is applicable to each step of the multi-stage rearrangement rather than to the summary rearrangement process.

Electrospray low energy CID and MALDI PSD fragmentations of protonated sulfinamide cross-linked peptides

Murine S100A8 (A8) is a major cytoplasmic neutrophil protein and is converted to novel oxidation products containing Cys–ε amino–Lys sulfinamide cross-links and Met–sulfoxide by the neutrophil oxidant HOCl. Seven products were separated using RP-HPLC, with electrospray ionization mass spectrometry (ESI-MS) masses after deconvolution of 10,354, 10,388, ±1, and 20,707, ±3 Da, and all were resistant to reduction by dithiothreitol. The major products with masses of 10,354 Da contained Cys 41–Lys 34/35 intramolecular cross-links. Additional isomeric products with identical masses (10,354 Da) were isolated and peptide mapping and ESI/MS indicated that Cys 41 forms covalent sulfinamide cross-links with either Lys 6, Lys 76, Lys 83, or Lys 87 present in A8. Electrospray low energy collisionally induced (CID) spectra of multiply-charged AspN digest peptides with sulfinamide cross-links contained characteristic fragmentations that corresponded to simple cleavage of the nitrogensulfur bond with charge retention on either of the fragment ions, allowing conformation of cross-linked peptides. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) post source decay spectra of [M + H] + ions of the same sulfinamide-containing cross-linked peptides fragment similarly, but additional facile fragmentation reactions corresponding to formation of a protonated peptide containing de-hydroalanine were attributed to cleavage of the carbonsulfur bond. In addition, lose of methanesulfenic acid from Met–sulfoxide was observed. A sulfinamide-containing adduct was isolated after incubation of the A8/HOCl reaction mixture with Lys or α N-acetyl Lys with masses of 10,500 or 10,542 Da. ESI/MS/MS and MALDI/ post decay source (PSD) analysis of A8 32–57–sulfinamide showed the same characteristic fragmentations as those in the sulfinamide cross-linked peptides, confirming the Cys 41–Lys sulfinamide cross-link and suggesting that peptide–peptide sulfinamides may all fragment similarly, allowing ready identification of these cross-links in proteins from more complex biological materials.