Intramolecular Fragmentation Research Articles

Complexes with Atomic Gold Ions: Efficient Bis-Ligand Formation.

Complexes of atomic gold with a variety of ligands have been formed by passing helium nanodroplets (HNDs) through two pickup cells containing gold vapor and the vapor of another dopant, namely a rare gas, a diatomic molecule (H2, N2, O2, I2, P2), or various polyatomic molecules (H2O, CO2, SF6, C6H6, adamantane, imidazole, dicyclopentadiene, and fullerene). The doped HNDs were irradiated by electrons; ensuing cations were identified in a high-resolution mass spectrometer. Anions were detected for benzene, dicyclopentadiene, and fullerene. For most ligands L, the abundance distribution of AuLn+ versus size n displays a remarkable enhancement at n = 2. The propensity towards bis-ligand formation is attributed to the formation of covalent bonds in Au+L2 which adopt a dumbbell structure, L-Au+-L, as previously found for L = Xe and C60. Another interesting observation is the effect of gold on the degree of ionization-induced intramolecular fragmentation. For most systems gold enhances the fragmentation, i.e., intramolecular fragmentation in AuLn+ is larger than in pure Ln+. Hydrogen, on the other hand, behaves differently, as intramolecular fragmentation in Au(H2)n+ is weaker than in pure (H2)n+ by an order of magnitude.

X-ray photoabsorption-induced processes within protonated rifamycin sodium salts in the gas phase

Up to now, the response of antibiotics upon ionizing radiation has been very scarcely reported. Here, we present the results of X-ray photoabsorption experiments on isolated rifamycin, a broad-range antibiotic against Gram-positive and Gram-negative bacteria. A mass spectrometer has been coupled to a synchrotron beamline to analyze cationic products of photoabsorption on protonated rifamycin dimer and monomer sodium salts. Absorption of a single photon in the 100–300eV energy range leads to ionization of the molecular system, followed by vibrational energy deposition and subsequent inter- and/or intramolecular fragmentation. Interestingly, we observe a proton transfer from sodiated rifamycin to rifamycin, a widely observed process in ionized molecular systems in the gas phase. Moreover, we show that another charge-transfer process occurs in both dimer and monomer: intramolecular sodium transfer, which has not been reported yet, to the best of our knowledge.

Cyclizations and fragmentations in the alkylation of 6-chloro-5-hydroxy-4-aminopyrimidines with aminoalkyl chlorides.

Substituted aminopyrimidines are an important class of compounds, in part because they frequently show biological activity. Facile synthesis of polysubstituted aminopyrimidines is highly desirable for the synthesis of screening libraries. We describe a route to 4,6‐diamino‐5‐alkoxypyrimidines via a SNAr‐alkylation‐SNAr sequence from readily available 4,6‐dichloro‐5‐methoxypyrimidine, which allows the synthesis of such compounds with regiochemical control. The extension of this approach to alkylating agents bearing amino substituents led to unexpected and, in some cases, unprecedented products resulting from intramolecular SNAr cyclization and subsequent fragmentation.

Experimental and Computational Studies of Dissociation Behavior and Structures of [M·pSer]+ (M = Li, Na, Ag, Rb, and Cs) Complexes

Complexes of metal monocations and phosphoserine (pSer) were generated by electrospray ionization (ESI), and were subjected to collision‐induced dissociation (CID). The primary fragmentation pathways of [Li·pSer]+, [Na·pSer]+, and [Ag·pSer]+ are dephosphorylation, dehydration, and Ser residue loss whereas metal ion loss is dominant for [Rb·pSer]+ and [Cs·pSer]+. Density functional theory (DFT) calculations suggest a correlation between structures, ion‐ligand binding energies, and fragmentation behavior: [Li·pSer]+, [Na·pSer]+, and [Ag·pSer]+, which exhibit a preference for charge‐solvated structures, have high binding energies and dissociate through intramolecular fragmentation of the ligand, whereas [Rb·pSer]+ and [Cs·pSer]+ likely have salt‐bridge structures with low binding energies, making the metal ion loss the dominant dissociation channel. Calculations also suggest that the salt‐bridge structure of [Na·pSer]+ may be present in the current work.

Irradiation of isolated collagen mimetic peptides by x rays and carbon ions at the Bragg-peak energy

We report on an experimental irradiation of isolated peptides by carbon ions at the Bragg-peak energy. Collagen mimetic peptides and their noncovalent complexes undergo nondissociative ionization, but also inter- and intramolecular fragmentation induced by internal energy transfer. We also detect nondissociative proton detachment, an ion-specific process. The average amount of energy transferred by ions is similar to the case of x-ray single photoabsorption, and our results indicate that it changes with the conformation and size of a given molecular system. Our work paves the way to experimental investigation of high-energy ion collisions involving proteins and DNA strands, to investigate the role of ion kinetic energy in internal energy deposition.

A Novel Allyl Transfer Coupled with a Grob Fragmentation.

A novel acid-promoted rearrangement is disclosed. In the previously unknown transformation, an allyl group migrated to an in situ formed carbocation stabilized by an electron-rich aryl or heteroaryl group, resulting in a stereoselective intramolecular Grob fragmentation. The outcome of the rearrangement observed with an array of substrates can be satisfactorily rationalized using a working hypothesis with the aid of a six-membered transition state similar to those proposed for the anionic oxy-Cope or oxonia-Cope rearrangements, but involving only one instead of two double bonds.

2,5-dihydroxybenzoic acid salts for matrix-assisted laser desorption/ionization time-of-flight mass spectrometric lipid analysis: simplified spectra interpretation and insights into gas-phase fragmentation.

In the last decades the interest in lipids as important components of membranes has considerably increased. Nowadays, lipids are often routinely analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In this regard, many relevant aspects are so far unknown, e.g., gas-phase stabilities, adduct formation and fragmentation. To fill this gap, MALDI matrix salts are presented which allow for simplified lipid analysis and elucidation of the underlying gas-phase fragmentation mechanisms. MALDI-TOF MS was used due to its beneficial properties for lipid investigations, e.g., high sensitivity, simple sample preparations, and a high tolerance to contaminants. The lipid hydrolysis, ionization and fragmentation properties of synthesized near neutral Na(+) and NH4 (+) salts of the commonly used MALDI matrix 2,5-dihydroxybenzoic acid were compared to that of DHB free acid itself as well as to base addition to DHB during dried-droplet sample preparation. Many lipid classes such as sterols, triacylglycerols, phosphatidylcholines and -ethanolamines undergo initial protonation with subsequent prompt partial up to quantitative fragmentation when analyzed with classical acidic matrices by MALDI-TOF MS. Neutral matrix salts can prevent initial analyte fragmentation by suppression of analyte protonation. Additionally, intramolecular gas-phase fragmentation reactions can be inhibited due to analyte stabilization by cation chelation. Base addition during sample preparation leads not only to in situ generation of matrix salts but also to analyte hydrolysis. Neutral DHB salts avoid separation of lipid species into several ionization states when used as matrices in MALDI-TOF MS. This allows for simplified lipid spectra interpretation. Due to the high cationization efficiency of DHB matrix salts, certain lipid classes become detectable which cannot be analyzed easily using standard acidic DHB.

Photoinduced Electron-Transfer-Promoted Redox Fragmentation of N-Alkoxyphthalimides

A new photoinduced electron-transfer-promoted redox fragmentation of N-alkoxyphthalimides has been developed. Mechanistic experiments have established that this reaction proceeds through a unique concerted intramolecular fragmentation process. This distinctive mechanism imparts many synthetic advantages, which are highlighted in the redox fragmentation of various heterocyclic substrates.

Ionic Chemistry of Tetravinylsilane Cation (TVS+) Formed by Electron Impact: Theory and Experiment

We performed experimental and ab initio studies on tetravinylsilane cation (TVS(+)) and its ionic and neutral fragmentation products. The aim of the study is the assignment of the products formed in electron impact ionization reaction of TVS. The experimental data were compared with ab initio data calculated at the MP2/cc-pVDZ level of theory. We found good agreement between the calculated reaction enthalpies and experimental appearance energies of the ions. More generally, our calculations reveal that there is a competition between intramolecular isomerization and fragmentation processes occurring after ionization of TVS, leading to the formation of a multitude of neutral and ionic species important for characterizing the silicon-carbon-containing plasma and media. New routes for the synthesis of bearing silicon molecules are suggested.

Photolytic, autocatalyzed decomposition of benzylic dialkoxy disulfides

The dialkoxy disulfide moiety has been shown to go through an intramolecular fragmentation to liberate trappable S 2, and can yield an alkoxy radical under photolytic conditions. We have examined a family of benzylic dialkoxy disulfides (X–Ph–CH 2–O–S–S–O–CH 2–Ph–X) under photolytic conditions and observed a correlation of decomposition based upon the substituent. We have been able to show that the decomposition is autocatalyzed and has a parabolic correlation with Swain and Lupton’s field constant, F .

Mechanisms of Air Oxidation of Ethoxylated Surfactants—Computational Estimations of Energies and Reaction Behaviors

Pathways for formation of previously observed autoxidation products of ethoxylated surfactants have been studied by DFT (B3LYP). In addition to the established radical-chain reaction, several mechanistic possibilities for intramolecular fragmentation of the intermediate radicals have been characterized concerning reaction barriers and energies of transition states. The results can rationalize the formation of previously observed autoxidation products, including several, which have been implicated as strongly allergenic.

Synthesis of angularly fused cyclopentanoids and analogous tricycles via photoinduced ketyl radical/radical anion fragmentation–cyclization reactions

Angular fused tricycles were synthesized through intramolecular tandem fragmentation–cyclization reactions by photochemically induced electron transfer (PET) of tricyclic α-cyclopropyl ketones with an unsaturated side chain at the position γ to the carbonyl group. The reactions resulted in regioselective cleavage of a β-cyclopropyl bond with formation of angular fused tricyclic ring systems via ketyl radical/radical anions as reactive intermediates. In general, triethylamine (TEA) was used as a strong reducing reagent in acetonitrile. The preferred regioselectivity of the cyclization step ( exo vs endo) depending on the substitution pattern at the quaternary carbon center (Cβ′) of the tricyclic α-cyclopropyl ketones was investigated. In addition, we also checked a two-step pathway for the synthesis of angular dioxa-triquinanes including photolysis of an allyloxy-substituted cyclopenta[ c]furanone derivative and subsequent β-cleavage of the resulted dioxa-[4.5.5.5]fenestrane under reductive PET conditions.

Ab initio photoionization dynamics of β-alanine

Photoionization dynamics of beta-alanine is studied by the trajectory simulations using the ab initio potential energy surface. Vertical photoionization in the spirit of the Franck-Condon principle is assumed both for the adiabatic and thermostatic simulations. Both intramolecular proton transfer and fragmentation while only the proton transfer are found in the thermostatic and adiabatic simulations, respectively, for the conformer having the intramolecular hydrogen bond N...H-O. The theoretical predictions are in line with the experimental observations available in the literatures. It is reported for the first time that the thermostatic temperatures strongly affect the fragmentation processes induced by photoionization.

The methoxycarbonylcarbene insertion into 1,3-dithiolane and 1,3-oxathiolane rings

Treatment of substituted 1,3-dithiolanes and 1,3-oxathiolanes with methyl diazoacetate in the presence of Rh 2(OAc) 4 effects ring expansion to the corresponding substituted 1,4-dithiane-2-carboxylates and 1,4-oxathiane-3-carboxylates. The sulfur ylides initially generated in these reactions undergo Stevens rearrangement in competition with both [2,3]-C–C-sigmatropic rearrangement and intramolecular fragmentation. In the case of 2-styryl-substituted 1,3-oxathiolane and 1,3-dithiolane, ring expansion on one-, three- and four-carbons subsequently takes place.

Synthesis of copolymers of tert‐butyl vinyl ether with maleic and citraconic anhydrides

AbstractIn the present study, the effects of charge‐transfer complex formation and intramolecular fragmentation (side‐chain lactonization) in radical copolymerization of tert‐butyl vinyl ether (t‐BVE) with anhydrides of maleic (MA) and citraconic (CA) acids and the structure–thermal behavior relationships of the resulting copolymers were examined using the 1H‐NMR, FTIR, DSC, and TGA analysis methods. It was shown that copolymerization under the chosen conditions proceeded through intramolecular fragmentation with the formation of γ‐lactone units. Side‐chain fragmentation of t‐BVE–MA and t‐BVE–CA copolymers also was confirmed by TGA and DSC analysis. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2455–2463, 2006 2006

Intramolecular isobaric fragmentation: a curiosity of accurate mass analysis of sulfadimethoxine in pond water.

Liquid chromatography with time-of-flight mass spectrometry (TOF-MS) and quadrupole-time-of-flight (Q-TOF) mass spectrometry/mass spectrometry (MS/MS) were used for the accurate mass analysis of sulfadimethoxine in pond water of a fish hatchery. Sulfadimethoxine is the most important sulfa antimicrobial used in aquaculture to treat bacterial disease in a wide variety of fish. Because correct identification is essential to environmental monitoring of antimicrobial pharmaceuticals, accurate mass analyses (TOF and Q-TOF-MS/MS) were compared to nominal mass measurement (quadrupole ion trap). It was known that all six members of the sulfa antimicrobial family gave a common 6-sulfanilamido ion at a nominal mass of m/z 156; thus, this ion was the focus of TOF confirmation (exact mass 156.0119 u) along with the protonated molecule (exact mass 311.0814 u). In the process of accurate mass confirmation of the 156 m/z fragment ion, a second isobaric ion (exact mass m/z 156.0773), was discovered at the same nominal mass, which was not differentiated by quadrupole ion trap. The structure was assigned as 2-4-dimethoxypyridine and is exactly the other protonated half of the sulfadimethoxine molecule. This discovery led to the subsequent use of Q-TOF-MS/MS and high-resolution identification of five other important ion fragments for the identification of sulfadimethoxine in pond water at environmental concentrations. The caveats of using low-resolution mass spectrometry without MS/MS for environmental monitoring are discussed in the light of high profile monitoring of sulfa antimicrobial pharmaceuticals in the aquatic environment.

Theoretical investigation of intramolecular trapping of strain allene: endo-bicyclo[3.2.1]octa-2,3-dien-6-ol

Quantum chemical calculations at the semiempirical PM3, PM5 and the molecular density functional, B88-PW91 and B88-LYP levels were performed on possibilities of intramolecular trapping and fragmentation products of endo -bicyclo[3.2.1]octa-2,3-dien-6-ol 1 by concerted reaction mechanism. The results have indicated that cyclohexa-2,4-dien-1-ylacetaldehyde 3 and (5Z)-octa-1,5-dien-7-yn-3-ol 4 are competitive reactions and appear more favour than the intramolecular trapping product 2-oxatricyclo[4.2.1.0 3,8 ]non-4-ene 2 according to PM3 and B88-LYP levels.

Fragmentation studies of noncovalent sugar–sugar complexes by infrared atmospheric pressure MALDI

An investigation of sugar–sugar noncovalent complex fragmentation was conducted using a 2.94 μm Er:YAG laser for infrared (IR) atmospheric pressure matrix-assisted laser desorption/ionization (AP MALDI) on an ion trap mass spectrometer (ITMS). This approach allowed the analysis of weak noncovalent complexes between a variety of biologically relevant oligosaccharides. The strength of interaction varied with different sugar structures, potentially due to varying strength of hydrogen bonding networks. In some cases, fragmentation of intramolecular sugar bonds preceded breakdown of the noncovalent complex. This result appeared primarily when complexes contained sugars with at least one sialic acid. Globotrios dimers also showed intramolecular fragmentation in preference to breakdown of the noncovalent dimer. This technique will allow further study of sugar–sugar interactions known to play a role in cellular interactions.

Pathways of reductive fragmentation of heterocyclic nitroarylmethyl quaternary ammonium prodrugs of mechlorethamine.

Nitroarylmethyl quaternary (NMQ) ammonium salts have potential as prodrugs for enzymatic or radiolytic reduction to release amine effectors under hypoxia. Earlier studies demonstrated one-electron release of the cytotoxic amine mechlorethamine (HN2) from 4-nitroimidazolyl and 2-nitropyrrolyl NMQ prodrugs (but not from nitrobenzyl analogs) through intramolecular electron transfer. In this study we determined whether this is a general feature of heterocyclic NMQ prodrugs of HN2 and examined the reductive pathways in detail using pulse and steady-state radiolysis. The kinetics of radical fragmentation varied by more than four orders of magnitude, independently of the one-electron reduction potential, within the series of eight nitroheterocycles examined. In addition to the compounds identified previously, new 2-nitropyrrole and 3-nitrothiophene NMQ prodrugs were found to provide efficient HN2 release (G > 0.5 micromol/J in anoxic formate buffer). However, the nitrothiophene was sensitive to nucleophilic displacement of HN2, making it less promising. Product analysis by HPLC/mass spectrometry identified symmetrical dimers arising from benzyl-type radical intermediates but also demonstrated that these dimers are not reliable markers for the intramolecular fragmentation of the initial nitro radical anion. This study elucidated multiple competing pathways for reductive fragmentation of NMQ prodrugs and identified the preferred electron acceptors for use in the development of analogs that release more potent cytotoxins.

Propensity of 4-Methoxy-4-vinyl-2-cyclopentenones Housed in Tri- and Tetracyclic Frameworks for Deep-Seated Photochemical Rearrangement

The excited-state behavior of a select group of highly enantioenriched tri- and tetracyclic 2-cyclopentenones has been examined in two solvents. Prepared by a convergent pathway involving the coupling of cyclopentenyl bromide 12 to several chiral ketones followed by desilylation, perruthenate oxidation, and ring-closing metathesis, the reactants were conveniently irradiated through quartz. Following promotion to the triplet level, a cyclopropylcarbinyl biradical intermediate is presumably generated provided that the double bond linked to C4 is not saturated. Four pathways have been observed to operate, only one of which has been observed previously under rather different conditions. The new photorearrangements include non-Norrish fragmentation to a ketene, generation of a spirocyclic intermediate, and ring expansion to a cyclobutyl radical in advance of intramolecular fragmentation of the four-membered ring. In the latter instance, a hydroazulenone derivative is formed. In the majority of the examples, pr...