Radical Rearrangement Research Articles

Extensive fragmentation of pheophytin-a by infrared multiphoton dissociation tandem mass spectrometry.

In a previous tandem mass spectrometry (MS/MS) study on chlorophyll-a, infrared multiphoton dissociation (IRMPD) was demonstrated as a more effective fragmentation method than collision-induced dissociation (CID) and electron-induced dissociation (EID), where odd-electron product ions were observed ubiquitously in CID and IRMPD. To further understand the role of the macrocycle and the central Mg atom in the MS/MS process, the fragmentation behaviour of pheophytin-a, the Mg-free chlorophyll-a, was investigated. CID, IRMPD, and EID were applied to the singly protonated pheophytin-a using an ultra-high-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. The result is compared with the MS/MS study of chlorophyll-a. For pheophytin-a, some different fragmentation patterns from chlorophyll-a were obtained by all three MS/MS methods, but IRMPD still appears the most efficient method of generating product ions. The detection of odd-electron fragments in the CID and IRMPD spectra of protonated pheophytin-a suggests that the macrocyclic structure effectively stabilizes radicals, and these radical ions seem to have a relatively higher abundance in the presence of the central Mg atom. The strong absorption in the infrared region of pheophytin-a and secondary free radical rearrangement are proposed to explain the extensive frgmentation in IRMPD spectra. In addition, a comparison of the IRMPD spectra of chlorophyll-a and pheophytin-a shows that the macrocycle in the absence of the Mg atom is much more fragile.

Aryl-substituted dimethylbenzimidazolines as effective reductants of photoinduced electron transfer reactions

Photoinduced electron transfer (PET) reactions promoted by 2-aryl substituted 1,3-dimethylbenzimidazolines (Ar-DMBIH) were investigated. Excited states of Ar-DMBIH, formed by irradiation using light above 360 nm, initiate PET reductions of various organic substrates, including transformations of epoxy ketones to aldols, free radical rearrangements such as the Dowd-Beckwith ring-expansion and 5-exo hexenyl cyclization, deprotection of N-sulfonyl-indols, and allylation of acyl formates. In these processes, Ar-DMBIH possessing 1-naphthyl, 2-naphthyl, 1-pyrenyl and 9-anthryl substituents formally act as two electron and one proton donors while the hydroxynaphthyl substituted derivative serves as a two electron and two proton donor. On the basis of the results of absorption spectroscopy studies, cyclic voltammetry and DFT calculation, a mechanistic sequence for these reduction reactions is proposed that involves initial photoexcitation of the aryl chromophore of the Ar-DMBIH followed by single electron transfer (SET) to the organic substrate to generate the radical cation of benzimidazoline and the radical anion of the substrate.

Formation of highly oxidized multifunctional compounds: autoxidation of peroxy radicals formed in the ozonolysis of alkenes – deduced from structure–product relationships

Abstract. It has been postulated that secondary organic particulate matter plays a pivotal role in the early growth of newly formed particles in forest areas. The recently detected class of extremely low volatile organic compounds (ELVOC) provides the missing organic vapors and possibly contributes a significant fraction to atmospheric SOA (secondary organic aerosol). The sequential rearrangement of peroxy radicals and subsequent O2 addition results in ELVOC which are highly oxidized multifunctional molecules (HOM). Key for efficiency of such HOM in early particle growth is that their formation is induced by one attack of the oxidant (here O3), followed by an autoxidation process involving molecular oxygen. Similar mechanisms were recently observed and predicted by quantum mechanical calculations e.g., for isoprene. To assess the atmospheric importance and therewith the potential generality, it is crucial to understand the formation pathway of HOM. To elucidate the formation path of HOM as well as necessary and sufficient structural prerequisites of their formation we studied homologous series of cycloalkenes in comparison to two monoterpenes. We were able to directly observe highly oxidized multifunctional peroxy radicals with 8 or 10 O atoms by an Atmospheric Pressure interface High Resolution Time of Flight Mass Spectrometer (APi-TOF-MS) equipped with a NO3−-chemical ionization (CI) source. In the case of O3 acting as an oxidant, the starting peroxy radical is formed on the so-called vinylhydroperoxide path. HOM peroxy radicals and their termination reactions with other peroxy radicals, including dimerization, allowed for analyzing the observed mass spectra and narrowing down the likely formation path. As consequence, we propose that HOM are multifunctional percarboxylic acids, with carbonyl, hydroperoxy, or hydroxy groups arising from the termination steps. We figured that aldehyde groups facilitate the initial rearrangement steps. In simple molecules like cycloalkenes, autoxidation was limited to both terminal C atoms and two further C atoms in the respective α positions. In more complex molecules containing tertiary H atoms or small, constrained rings, even higher oxidation degrees were possible, either by simple H shift of the tertiary H atom or by initialization of complex ring-opening reactions.

Laccase-Catalyzed Degradation of Perfluorooctanoic Acid

This study examined the decomposition of perfluorooctanoic acid (PFOA) in enzyme-catalyzed oxidative humification reactions (ECOHRs). ECOHRs make up a class of reactions that are ubiquitous in the environment. Approximately 50% of PFOA in a mineral buffer solution decomposed upon addition of laccase and 1-hydroxybenzotriazole after 157 days with a pseudo-first-order rate constant of 0.0044 day–1 (r2 = 0.89). No shorter carbon-chain perfluorocarboxylic acids were detected as degradation products during the experiment. However, partially fluorinated shorter-chain alcohols and aldehydes were identified by high-resolution mass spectrometry. These partially fluorinated compounds were likely products resulting from PFOA degradation via a combination of free radical decarboxylation, rearrangement, and coupling processes. Fluoride was detected in the reaction solution, and the concentration indicated a 28.2% defluorination ratio during the treatment. This finding suggests that PFOA may be transformed during humif...

Probing reversible chemistry in coenzyme B12 -dependent ethanolamine ammonia lyase with kinetic isotope effects.

Coenzyme B12-dependent enzymes such as ethanolamine ammonia lyase have remarkable catalytic power and some unique properties that enable detailed analysis of the reaction chemistry and associated dynamics. By selectively deuterating the substrate (ethanolamine) and/or the β-carbon of the 5′-deoxyadenosyl moiety of the intrinsic coenzyme B12, it was possible to experimentally probe both the forward and reverse hydrogen atom transfers between the 5′-deoxyadenosyl radical and substrate during single-turnover stopped-flow measurements. These data are interpreted within the context of a kinetic model where the 5′-deoxyadenosyl radical intermediate may be quasi-stable and rearrangement of the substrate radical is essentially irreversible. Global fitting of these data allows estimation of the intrinsic rate constants associated with CoC homolysis and initial H-abstraction steps. In contrast to previous stopped-flow studies, the apparent kinetic isotope effects are found to be relatively small.

Reaction of Pyridoxal-5′-phosphate-N-oxide with Lysine 5,6-Aminomutase: Enzyme Flexibility toward Cofactor Analog

Lysine 5,6-aminomutase (5,6-LAM) is a 5′-deoxyadenosylcobalamin and pyridoxal-5′-phosphate (PLP) codependent radical enzyme that can accept at least three substrates, d-lysine, l-β-lysine and l-lysine. The reaction of 5,6-LAM is believed to follow an intramolecular radical rearrangement mechanism involving formation of a cyclic azacyclopropylcarbinyl radical intermediate (I•). Similar I•s are also proposed for other radical aminomutases, such as ornithine 4,5-aminomutase (4,5-OAM) and lysine 2,3-aminomutase (2,3-LAM). Nevertheless, experimental proof in support of the participation of I• have been elusive. PLP is proposed to lower the energy of this elusive I• by captodative stabilization and spin delocalization. In this work, we employ PLP-N-oxide (PLP-NO) to investigate the flexibility of 5,6-LAM toward cofactor analog and participation of I• in the reaction mechanism. Our calculations show that substitution of PLP-NO for PLP stabilizes I• by 35.2 kJ mol–1 as a result of enhanced spin delocalization, wh...

Probing Peptide Cation–Radicals by Near-UV Photodissociation in the Gas Phase. Structure Elucidation of Histidine Radical Chromophores Formed by Electron Transfer Reduction

Electron transfer reduction of gas-phase ions generated from histidine-containing peptides forms stable cation-radicals that absorb light at 355 nm, as studied for AAHAR, AAHAK, DSHAK, FHEK, HHGYK, and HHSHR. Laser photodissociation of mass-selected cation-radicals chiefly resulted in loss of H atoms, contrasting dissociations induced by slow collisional heating. The 355 nm absorption was due to new chromophores created by electron transfer and radical rearrangements in the cation-radicals. The chromophores were identified by time-dependent density functional theory calculations as 2H,3H-imidazoline and 2H-dihydrophenol radicals, formed by hydrogen atom transfer to the histidine and tyrosine side chain groups, respectively. These radicals undergo facile C-H bond dissociations upon photon absorption. In contrast, dissociations of histidine peptide cation-radicals containing the 1H,3H-imidazoline ring prefer loss of 4-methylimidazole via a multistep reaction pathway. The isomeric cation-radicals can be distinguished by a combination of collision-induced dissociation and near-UV photodissociation. The TD-DFT excitation energies in model imidazoline radicals were benchmarked on EOM-CCSD energies, and a satisfactory agreement was found for the M06-2X and ωB97XD functionals. The combination of electron transfer, photodissociation, collisional activation, and theory is presented as a powerful tool for studying structures and electronic properties of peptide cation-radicals in the gas phase.

Iron- or silver-catalyzed oxidative fluorination of cyclopropanols for the synthesis of β-fluoroketones.

The Fe(III)- or Ag(I)-catalyzed oxidative fluorination of cyclopropanols via radical rearrangement is disclosed. This process features a straightforward and highly effective protocol for the site-specific synthesis of β-fluoroketones and represents an expedient method for the synthesis of γ-, δ- and ε-fluoroketones. Notably, this reaction proceeds at room temperature and tolerates a diverse array of cyclopropanols.

Stabilization of long-chain intermediates in solution. Tridecyl radicals and cations

Tetradecanoic acid was decarboxylated by means of lead(IV) acetate (LTA) under thermal (81°C) and photolytic (r.t.) conditions in benzene solution. The mixture of products, obtained in thermal reaction, consists of esters (acetoxyalkanes and carboxylates), tridecenes, tridecane and phenyltridecane. Additionally, tetradecane and hexacosane, under photolytic conditions, were formed. The classes of products and their distribution might be explained by presence of intermediate 1-tridecyl radical which can undergo intramolecular (result in formation of rearranged carbon centered radicals) and intermolecular stabilization pathways. Experimentally obtained results were used as input data for computational Monte Carlo simulation study of the reaction. On the basis of these results, radical rearrangements, as well as hydride shifts in tridecyl system are discussed.

The Challenge of Human Resource Development in Nigeria’s Sustainable Transformation Agenda

In the recent times, the Nigerian Government has shown serious concern in the pursuit of sustainable transformation that will ensure full and effective utilization of its abundant resources which will translate into better living standards for the masses. Sustainable transformation is a mandate for a radical, structural and fundamental rearrangement and re-ordering of the building blocks of the nation. This paper, anchored on the human capital theory, argues that Human Resource Development (HRD) constitutes a vital ingredient in the development of any society. At the macro level of the society HRD rests on the pillars of education, the family and national leadership to inculcate the right skill, knowledge, value and attitude in the citizenry. It is further argued that the issues of inadequate skill and knowledge, poor value and attitude are indications of the failure of the educational, family and leadership systems, and are HRD challenges capable of hindering the achievement of the goals of the transformation agenda. The paper concludes that to ensure the success of the transformation agenda, there is need to address the deficiencies in the HRD of the masses through radical transformation of the educational system; reorientation of leaders and masses towards positive values and attitudes; and re-awakening of the family institution to its traditional responsibility, all of which will translate into a culture of ‘doing the right things’ and ‘doing the things right’.

Radical serotype rearrangement of carried pneumococci in the first 3 years after intensive vaccination started in Hungary.

Streptococcus pneumoniae is responsible for a significant amount of morbidity and mortality worldwide. Healthy carriers, mainly young children, are the most important sources of infections. In the current study, we aimed to determine the changes that have occurred since the introduction of PCV-7 in Hungary. Nasal specimens were collected from 1,022 healthy children aged 3-6 years attending day-care centres. After thorough identification, pneumococcal isolates were serotyped, and their antibiotic sensitivity was determined. The carriage rate was found to be 34.9%. A huge serotype rearrangement was detected compared to earlier results, with the previously leading serotype 14 having completely disappeared. Serotypes 11A, 35F, 19A, 6B, 15B, 3 and 38 were most prevalent, and 29 different types were identified in total. The PCV-7 types were responsible for 16.5% of all serotypes, and 36.0% are not covered by any pneumococcal vaccines. The isolates were sensitive to most tested antibiotics, except erythromycin (resistance was 21.6%). Only one penicillin-resistant strain was found. The newly and rapidly emerging non-vaccine serotypes are much more sensitive, except serotype 19A. Due to PCV vaccination, a complete serotype arrangement occurred also in Hungary. The old "paediatric" serotypes were replaced by serotypes 11A, 35F, 19A, 6B, 15B, 3 and 38.

Mechanism of Fast Pyrolysis of Lignin: Studying Model Compounds

Fast pyrolysis of lignin is one of the most promising methods to convert the complex and irregular structure of lignin into renewable chemicals and fuel. During pyrolysis the complex set of radical reactions, rearrangements, and eliminations is influenced by temperature, pressure, and the lignin origin and structure. This model compound study aims to understand reaction pathways and how primary intermediates lead to the observed product selectivity. The pyrolysis microreactor directly connected to the gas chromatograph with a mass spectrometer (py-GC/MS) detects the final products, while imaging photoelectron photoion coincidence (iPEPICO) with VUV synchrotron radiation shows primary decomposition radicals. The tested model compounds, diphenylether (DPE) and ortho-methoxyphenol (guaiacol), represent a common lignin linkage and the most present subunit in lignin, respectively. Radical fragments, such as the hydroxycyclopentadienyl radical in guaiacol decomposition, are identified by mass-selected threshold photoelectron spectra (ms-TPES) in excellent agreement with the Franck-Condon simulation. While homolysis produces phenoxy-, phenyl-, and hydroxyphenoxy radicals, which are observed in high vacuum, radically initiated reactions are dominant in ambient conditions and produce recombination and rearrangement products, such as 2-hydroxybenzaldehyde in the case of guaiacol. The degree of substitution plays a dominant role in both the stabilization of the intermediate radical and the following degree of recombination. The recombination of phenoxy radicals is enhanced compared to hydroxy-phenoxy radicals.

Branding resources: extractive communities, industrial brandscapes and themed environments

As the labour process is mechanized and Fordist social contracts between company and workers erode, extractive communities bear increased costs while receiving fewer benefits. The authors use two case studies to elucidate how processes that characterize post-industrial culture elsewhere are now transforming the working landscapes of rural mining and timbering communities. Companies draw on branding techniques familiar to other contexts to evoke markets where none exist, and to link production practices with particular forms of identity. These branding strategies at the site of production attempt to simulate the paternalistic culture of a company town, in a themed environment that identifies the company with both locale and nation. These techniques allowed both companies in this article to extend temporary legitimacy in their practices, creating a sense of continuity despite the radical rearrangement and intensification of mining and timbering practices.

Correction to “Facile Rearrangement of 3-Oxoalkyl Radicals is Evident in Low-Temperature Gas-Phase Oxidation of Ketones”

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionCorrection to “Facile Rearrangement of 3-Oxoalkyl Radicals is Evident in Low-Temperature Gas-Phase Oxidation of Ketones”Adam M. Scheer*, Oliver Welz, Darryl Y. Sasaki, David L. Osborn, and Craig A. Taatjes*Cite this: J. Am. Chem. Soc. 2014, 136, 23, 8486Publication Date (Web):June 2, 2014Publication History Published online2 June 2014Published inissue 11 June 2014https://doi.org/10.1021/ja503987kCopyright © 2014 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views462Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (120 KB) Get e-Alerts Get e-Alerts

Nitrile Imines and Nitrile Ylides: Rearrangements of BenzonitrileN-Methylimine and Benzonitrile Dimethylmethylide to Azabutadienes, Carbodiimides, and Ketenimines. Chemical Activation in Thermolysis of Azirenes, Tetrazoles, Oxazolones, Isoxazolones, and Oxadiazolones

Flash vacuum thermolysis (FVT) of 1-methyl-5-phenyltetrazole (5b), 2-methyl-5-phenyltetrazole (1b), and 3-methyl-5-phenyl-1,3,4-oxadiazol-2(3H)-one (3b) affords the nitrile imine (2b), which rearranges in part to N-methyl-N'-phenylcarbodiimide (7b). Another part of 2b undergoes a 1,4-H shift to the diazabutadiene (13). 13 undergoes two chemically activated decompositions, to benzonitrile and CH2═NH and to styrene and N2. FVT of 2,2-dimethyl-4-phenyl-oxazol-5(2H)-one (16) at 400 °C yields 3-methyl-1-phenyl-2-azabutadiene (18) in high yield. In contrast, FVT of 3,3-dimethyl-2-phenyl-1-azirene (21) at 600 °C or 4,4-dimethyl-3-phenyl-isoxazolone (20) at 600 °C affords only a low yield of azabutadiene (18) due to chemically activated decomposition of 18 to styrene and acetonitrile. There are two reaction paths from azirene (21): one (path a) leading to nitrile ylide (17) and the major products styrene and acetonitrile and the other (path b) leading to the vinylnitrene (22) and ketenimine (23). The nitrile ylide PhC(-)═N(+)═C(CH3)2 (17) is implicated as the immediate precursor of azabutadiene (18). FVT of either 3-phenylisoxazol-5(4H)one (25) or 2-phenylazirene (26) at 600 °C affords N-phenylketenimine (28). The nitrile ylide PhC(-)═N(+)═CH2 (30) is postulated as a reversibly formed intermediate. N-Phenylketenimine (28) undergoes chemically activated free radical rearrangement to benzyl cyanide. The mechanistic interpretations are supported by calculations of the energies of key intermediates and transition states.

Unexpected Pyrolytic Behaviour of Substituted Benzo[c]thiopyran and Thieno[2,3-c]thiopyran S,S-dioxides

Flash vacuum pyrolysis (FVP) of benzo[c]thiopyran S,S-dioxide (1) results in formation of indene and 2-vinylbenzaldehyde as previously described. A range of eight analogues with various substitution patterns are found to behave differently. In general, there is no extrusion of SO2 to give products analogous to indene, but unsaturated carbonyl products analogous to 2-vinylbenzaldehyde are formed in most cases by way of ring expansion to a 7-membered ring sultine, extrusion of SO, and intramolecular hydrogen atom transfer. Other processes observed include formation of anthracene via an isomeric 7-membered sultine with loss of SO, CO and methane or butane, and formation of 4-ethylidene-4,5-dihydrocyclobuta[b]thiophenes by way of SO loss, a radical rearrangement, and extrusion of acetone. The analogues with a halogen substituent at position 8 on the benzene ring require a higher temperature to react and give naphthalene resulting from net elimination of HX and SO2. The X-ray crystal structure of 1 is also reported.

The phenolic metabolites of the anti-HIV drug efavirenz: Evidence for distinct reactivities upon oxidation with Frémy's salt

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor administered as first line treatment against HIV-1. The major drawbacks of EFV therapy are neurotoxicity and hepatotoxicity, which may result from bioactivation to reactive metabolites capable of reacting with bionucleophiles. We investigated the in vitro oxidation of the phenolic EFV metabolites, 7-hydroxy-efavirenz (7-OH-EFV) and 8-hydroxy-efavirenz (8-OH-EFV), with Frémy's salt. A quinoline derivative, 6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinolin-7-ol, presumably stemming from a radical rearrangement, was selectively obtained from 7-OH-EFV in 10% yield. In contrast, when subjected to the same oxidation conditions, 8-OH-EFV was considerably more prone to oxidative degradation and yielded multiple products. Among these, a quinone–imine derivative was tentatively identified upon LC–ESI–MS/MS analysis of the reaction mixture. These observations demonstrate a remarkable difference in the reactivities of the two phenolic EFV metabolites under oxidative conditions. Moreover, taking into consideration the toxicological significance of quinone–imine derivatives, these findings may explain earlier reports that 8-OH-EFV is a more potent toxicant than 7-OH-EFV in model test systems.

Mechanistic Insights from Reaction of α-Oxiranyl-Aldehydes with Cyanobacterial Aldehyde Deformylating Oxygenase

The biosynthesis of long-chain aliphatic hydrocarbons, which are derived from fatty acids, is widespread in Nature. The last step in this pathway involves the decarbonylation of fatty aldehydes to the corresponding alkanes or alkenes. In cyanobacteria, this is catalyzed by an aldehyde deformylating oxygenase. We have investigated the mechanism of this enzyme using substrates bearing an oxirane ring adjacent to the aldehyde carbon. The enzyme catalyzed the deformylation of these substrates to produce the corresponding oxiranes. Performing the reaction in D2O allowed the facial selectivity of proton addition to be examined by (1)H NMR spectroscopy. The proton is delivered with equal probability to either face of the oxirane ring, indicating the formation of an oxiranyl radical intermediate that is free to rotate during the reaction. Unexpectedly, the enzyme also catalyzes a side reaction in which oxiranyl-aldehydes undergo tandem deformylation to furnish alkanes two carbons shorter. We present evidence that this involves the rearrangement of the intermediate oxiranyl radical formed in the first step, resulting in aldehyde that is further deformylated in a second step. These observations provide support for a radical mechanism for deformylation and, furthermore, allow the lifetime of the radical intermediate to be estimated based on prior measurements of rate constants for the rearrangement of oxiranyl radicals.

Facile Rearrangement of 3-Oxoalkyl Radicals is Evident in Low-Temperature Gas-Phase Oxidation of Ketones

The pulsed photolytic chlorine-initiated oxidation of methyl-tert-butyl ketone (MTbuK), di-tert-butyl ketone (DTbuK), and a series of partially deuterated diethyl ketones (DEK) is studied in the gas phase at 8 Torr and 550-650 K. Products are monitored as a function of reaction time, mass, and photoionization energy using multiplexed photoionization mass spectrometry with tunable synchrotron ionizing radiation. The results establish that the primary 3-oxoalkyl radicals of those ketones, formed by abstraction of a hydrogen atom from the carbon atom in γ-position relative to the carbonyl oxygen, undergo a rapid rearrangement resulting in an effective 1,2-acyl group migration, similar to that in a Dowd-Beckwith ring expansion. Without this rearrangement, peroxy radicals derived from MTbuK and DTbuK cannot undergo HO2 elimination to yield a closed-shell unsaturated hydrocarbon coproduct. However, not only are these coproducts observed, but they represent the dominant oxidation channels of these ketones under the conditions of this study. For MTbuK and DTbuK, the rearrangement yields a more stable tertiary radical, which provides the thermodynamic driving force for this reaction. Even in the absence of such a driving force in the oxidation of partially deuterated DEK, the 1,2-acyl group migration is observed. Quantum chemical (CBS-QB3) calculations show the barrier for gas-phase rearrangement to be on the order of 10 kcal mol(-1). The MTbuK oxidation experiments also show several minor channels, including β-scission of the initial radicals and cyclic ether formation.

ChemInform Abstract: Bromine Radical‐Mediated Sequential Radical Rearrangement and Addition Reaction of Alkylidenecyclopropanes.

AbstractThis provides an efficient strategy on generation and utilization of homoallyl radicals.