Radical Cleavage Research Articles

Diatomic Iron with a Pseudo-Phthalocyanine Coordination Environment for Highly Efficient Oxygen Reduction over 150,000 Cycles.

Atomically dispersed Fe-N-C catalysts emerged as promising alternatives to commercial Pt/C for the oxygen reduction reaction. However, the majority of Fe-N-C catalysts showed unsatisfactory activity and durability due to their inferior O-O bond-breaking capability and rapid Fe demetallization. Herein, we create a pseudo-phthalocyanine environment coordinated diatomic iron (Fe2-pPc) catalyst by grafting the core domain of iron phthalocyanine (Fe-Nα-Cα-Nβ) onto defective carbon. In situ characterizations and theoretical calculation confirm that Fe2-pPc follows the fast-kinetic dissociative pathway, whereby Fe2-pPc triggers bridge-mode oxygen adsorption and catalyzes direct O-O radical cleavage. Compared to traditional Fe-N-C and FePc-based catalysts exhibiting superoxo-like oxygen adsorption and an *OOH-involved pathway, Fe2-pPc delivers a superior half-wave potential of 0.92 V. Furthermore, the ultrastrong Nα-Cα bonds in the pPc environment endow the diatomic iron active center with high tolerance for reaction-induced geometric stress, leading to significantly promoted resistance to demetallization. Upon an unprecedented harsh accelerated degradation test of 150,000 cycles, Fe2-pPc experiences negligible Fe loss and an extremely small activity decay of 17 mV, being the most robust candidate among previously reported Fe-N-C catalysts. Zinc-air batteries employing Fe2-pPc exhibit a power density of 255 mW cm-2 and excellent operation stability beyond 440 h. This work brings new insights into the design of atomically precise metallic catalysts.

Reduction of styrene compounds by hydrogen iodide

Reduction of styrene compounds was achieved by the simple method of adding more than 2.5 equivalents of an aqueous HI solution in chlorobenzene under refluxing conditions for 8 h to give the product in medium to excellent yields. There was no need to add further additional reagent and catalyst. HI was a specific reagent for this reduction reaction. Increment of the amount of HI was efficient to increase the yield rather than to elongate the reaction time. This reaction could be applied to compounds bearing halogen and sulfur atoms, which would act as reductive site and poisoning of the transition-metal catalyst, respectively. The yield was decreased in the case of the compounds bearing small substituent such as propyl and butyl groups on olefin. This reaction proceeded via the iodinated intermediate followed by the reduction of C-I bond. The reduction mechanism would contain the radical cleavage of the C-I bond.

THERMOCHEMICAL CONVERSION OF DIOXANLIGNIN OF WHEAT STRAW IN SUB/SUPERCRITICAL DIMETHYL CARBONATE MEDIUM

The aim of this work was to study the conversion processes of dioxanlignin of wheat straw in sub/supercritical dimethyl carbonate medium. The experiment was performed in autoclave in a temperature range from 200 to 350 °С. The low-molecular-weight products were extracted from liquid fraction using hexane. GC-MS was used to analyze their composition. The solid products were analyzed by IR-spectroscopy method. The low-molecular-weight products consist of esters, aldehydes, ketones and alkyl aromatic compounds. Thirty-four compounds were identified by GC-MS, including 12 compounds С6–С3, i.e. structures which relates to acknowledged phenylpropane structure of lignin. The composition of low-molecular-weight products fraction predominantly comprised of methyl esters of aromatic and fatty acids. More than 95% of identified low-molecular-weight products are veratrous-type compounds. New data on the conversion processes of dioxanlignin of wheat straw in sub/supercritical dimethyl carbonate medium were obtained. It is shown that high solubility of dioxanlignin under subcritical conditions can be caused by cleavage of intramolecular interaction, including hydrogen bonds between macromolecules of dioxanlignin, as a result of thermal exposure and methylation reactions. Fragmentation of molecules under supercritical conditions includes the processes of a radical cleavage of alkyl aryl ester bonds as well as the reactions of dealkylation, dehydration, methylation, re-esterification and demetoxylation.

Role of Hydroxyl Radical in Degradation of NTO: DFT Study.

Hydroxyl radicals are important reactive oxygen species produced in the aquatic environment under sunlight irradiation. Many organic pollutants may be decomposed as they encounter hydroxyl radicals, due to their high oxidative ability. NTO (5-nitro-1,2,4-triazol-3-one), an energetic material used in military applications, may be released to the environment and dissolved in surface water and groundwater due to its good water solubility. A detailed investigation of the possible mechanism for NTO decomposition in water induced by hydroxyl radical as one of the pathways for NTO environmental degradation was performed by computational study at the PCM/M06-2X/6-311++G(d,p) level. Decomposition of NTO was found to be a multistep process that may begin with an addition of hydroxyl radical to the carbon atom of C═N double bond and consequent release of a nitrite radical. The formed intermediate undergoes a series of chemical transformations that include the attachments of hydroxyl radical to carbon atoms, the transfer of hydrogen to hydroxyl radical, isomerization, and bond cleavage, leading to low-weight inorganic compounds, such as ammonia, nitrogen gas, nitrous acid, nitric acid, and carbon(IV) oxide. The anionic form of NTO is more reactive toward interaction with the hydroxyl radical as compared with its neutral form. Calculated activation energies and high exergonicity of the studied process support the significant contribution of the hydroxyl radical to NTO mineralization in environment.

Potential risk resulting from the influence of static magnetic field upon living organisms. Numerically simulated effects of the static magnetic field upon model complex lipids

Background: Recognising effects of static magnetic field (SMF) of varying flux density on flora and fauna is attempted. For this purpose, the influence of static magnetic field is studied for molecules of five complex lipids i.e. such as β-carotene, sphingosine, ceramide, cholesterol and phosphatidylcholine. Methods: Computations of the effect of real SMF 0.0, 0.1, 1, 10 and 100 AMFU (Arbitrary Magnetic Field Unit; here 1AMFU > 1000 T) flux density were performed in silico (computer vacuum), involving advanced computational methods. Results: SMF polarises molecules depending on applied flux density. Only β-carotene survives exposure to SMF of 10 and 100 AMFU without radical splitting of some valence bonds. Molecules of remaining lipids suffered radical cleavage of some bonds on exposure to SMF of 10 and 100 AMFU. Manipulation with applied flux density provides either inhibition or stimulation of biological functions of the lipids under study. Conclusions: SMF destabilises complex lipids to the extent depending applied flux density. Biological functions of β-carotene are fairly sensitive to SMF, whereas only slight response to the effect of SMF is observed in case of sphingosine, ceramide and cholesterol. Enzymatic hydrolysis of phosphatidylcholine is stimulated by SMF regardless of the catalysed enzyme employed.

Photocatalytic Hydro Tri/Difluoromethylation of Alkenes with Bench Stable Tri/Difluoromethylating Reagents.

Herein, we demonstrate the synthesis and characterization of bench stable tri/difluoromethylating reagents and their potential applications in redox neutral hydro tri/difluoromethylation of alkenes enabled by visible light. The new tri/difluoromethylating reagents are obtained on a gram-scale through simply cyclocondensation of commercially available anthranilamide with phenyltrifluoro or difluoromethyl ketone. Preliminary mechanistic studies indicated that a canonical photoredox catalytic cycle is being operative. DFT studies support this and further reveal that deprotonation occurs before radical cleavage. DFT studies also show that the better yield with HCF2 reagent is attributed to the favorable expulsion of the corresponding radical moiety.

Recent DFT Calculations on the Mechanism of Transition‐Metal‐Catalyzed C−O Activation of Alcohols

AbstractIn recent decades, density functional theory (DFT) calculations have been extensively employed to investigate the mechanism of transition metal‐catalyzed C−O activation reactions. These studies provide valuable insights into the structure‐reactivity/selectivity correlations via theoretical simulations and energy profile analysis. Alcohols, a category of molecules that are readily available from biomass and are low cost, represent one of the most extensively studied compounds in organic synthesis. In this review, we provide a brief overview of the DFT studies conducted since 2017 on the C−OH bond activation of alcohols catalyzed by transition metals. Specifically, the activation can be mainly divided into four categories: free radical cleavage, metal insertion, nucleophilic attack, and β‐OH elimination. We will also cover some promising strategies and give a perspective regarding future research directions in this field.

Swapping Copper-Catalytic Process: Selective Access to Pyrazoles and Conjugated Ketimines from Oxime Acetates and Cyclic Sulfamidate Imines.

A powerful CuCl-catalyzed sequential one-pot reaction of aryl methyl ketoxime acetates with cyclic N-sulfonyl imines followed by elimination in the presence of base is reported. This hydrazine-free method conveniently makes C-C and N-N bonds via a radical cleavage of the N-O bond, delivering a special class of C3-hydroxyarylated pyrazoles in good yields. Surprisingly, while employing CuI as a catalyst instead of CuCl, the reaction proceeds through a non-radical pathway which embodies a new tactic for the high-yielding access to value-added conjugated N-unsubstituted ketimines. Moreover, additive-free approach to sulfamidate-fused-pyrazoles was achieved by successfully catalyzing addition and oxidative N-N bond-making reactions by CuI and CuCl, respectively. Significantly, our novel technique could convert the prepared ketimines into the pharmacologically recognized 6H-benzo[c]chromene frameworks.

Synthesis of 2,2,6,6-Tetramethylpiperidin-1-yl-2-(2-cyanophenyl)-acetate by Transition Metal-Free Radical Cleavage Reaction from α-Bromoindanone

Synthesis of 2,2,6,6-Tetramethylpiperidin-1-yl-2-(2-cyanophenyl)-acetate by Transition Metal-Free Radical Cleavage Reaction from α-Bromoindanone

Visible Light-Induced Coupling Cyclization Reaction of α-Diazosulfonium Triflates with α-Oxocarboxylic Acids or Alkynes.

A photocatalyst-free radical cleavage of α-diazo sulfonium salts has been developed for the first time. The reaction provides an efficient method for the generation of diazomethyl radicals from α-diazosulfonium triflates under photochemical conditions. Utilizing the in situ generated diazomethyl radicals as key intermediate, the coupling cyclization reaction of α-diazosulfonium triflates with α-oxocarboxylic acids or alkynes has been achieved. The method affords a diverse set of important 2,5-disubstituted 1,3,4-oxadiazoles and 3,5-disubstituted-1H-pyrazoles with excellent regioselectivity in a single step. A reaction mechanism involving a radical pathway was further supported by control experiments and DFT calculations.

High-throughput mapping of RNA solvent accessibility at the single-nucleotide resolution by RtcB ligation between a fixed 5′-OH-end linker and unique 3′-P-end fragments from hydroxyl radical cleavage

ABSTRACT Given the challenges for the experimental determination of RNA tertiary structures, probing solvent accessibility has become increasingly important to gain functional insights. Among various chemical probes developed, backbone-cleaving hydroxyl radical is the only one that can provide unbiased detection of all accessible nucleotides. However, the readouts have been based on reverse transcription (RT) stop at the cleaving sites, which are prone to false positives due to PCR amplification bias, early drop-off of reverse transcriptase, and the use of random primers in RT reaction. Here, we introduced a fixed-primer method called RL-Seq by performing RtcB Ligation (RL) between a fixed 5′-OH-end linker and unique 3′-P-end fragments from hydroxyl radical cleavage prior to high-throughput sequencing. The application of this method to E. coli ribosomes confirmed its ability to accurately probe solvent accessibility with high sensitivity (low required sequencing depth) and accuracy (strong correlation to structure-derived values) at the single-nucleotide resolution. Moreover, a near-perfect correlation was found between the experiments with and without using unique molecular identifiers, indicating negligible PCR biases in RL-Seq. Further improvement of RL-Seq and its potential transcriptome-wide applications are discussed.

Phosphorylation Regulation of a Histone-like HU Protein from Deinococcus radiodurans.

Histone-like proteins are small molecular weight DNA-binding proteins that are widely distributed in prokaryotes. These proteins have multiple functions in cellular structures and processes, including the morphological stability of the nucleoid, DNA compactness, DNA replication, and DNA repair. Deinococcus radiodurans, an extremophilic microorganism, has extraordinary DNA repair capability and encodes an essential histone-like protein, DrHU. We aim to investigate the phosphorylation regulation role of a histone-like HU protein from Deinococcus radiodurans. LC-MS/MS analysis was used to determine the phosphorylation site of endogenous DrHU. The predicted structure of DrHU-DNA was obtained from homology modeling (Swissmodel) using Staphylococcus aureus HU-DNA structure (PDB ID: 4QJU) as the starting model. Two types of mutant proteins T37E and T37A were generated to explore their DNA binding affinity. Complemented-knockout strategy was used to generate the ΔDrHU/pk-T37A and ΔDrHU/pk-T37E strains for growth curves and phenotypical analyses. The phosphorylation site Thr37, which is present in most bacterial HU proteins, is located at the putative protein-DNA interaction interface of DrHU. Compared to the wild-type protein, one in which this threonine is replaced by glutamate to mimic a permanent state of phosphorylation (T37E) showed enhanced double-stranded DNA binding but a weakened protective effect against hydroxyl radical cleavage. Complementation of T37E in a DrHU-knockout strain caused growth defects and sensitized the cells to UV radiation and oxidative stress. Phosphorylation modulates the DNA-binding capabilities of the histone-like HU protein from D. radiodurans, which contributes to the environmental adaptation of this organism.

Extract of Acanthopanax senticosus and Its Components Interacting with Sulfide, Cysteine and Glutathione Increase Their Antioxidant Potencies and Inhibit Polysulfide-Induced Cleavage of Plasmid DNA.

Aqueous root extract from Acanthopanax senticosus (ASRE) has a wide range of medicinal effects. The present work was aimed at studying the influence of sulfide, cysteine and glutathione on the antioxidant properties of ASRE and some of its selected phytochemical components. Reduction of the 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazol-1-yloxy-3-oxide (●cPTIO) stable radical and plasmid DNA (pDNA) cleavage in vitro assays were used to evaluate antioxidant and DNA-damaging properties of ASRE and its individual components. We found that the interaction of ASRE and its two components, caffeic acid and chlorogenic acid (but not protocatechuic acid and eleutheroside B or E), with H2S/HS−, cysteine or glutathione significantly increased the reduction of the ●cPTIO radical. In contrast, the potency of ASRE and its selected components was not affected by Na2S4, oxidized glutathione, cystine or methionine, indicating that the thiol group is a prerequisite for the promotion of the antioxidant effects. ASRE interacting with H2S/HS− or cysteine displayed a bell-shaped effect in the pDNA cleavage assay. However, ASRE and its components inhibited pDNA cleavage induced by polysulfides. In conclusion, we suggest that cysteine, glutathione and H2S/HS− increase antioxidant properties of ASRE and that changes of their concentrations and the thiol/disulfide ratio can influence the resulting biological effects of ASRE.

Transition metals of arene derivatives with functionalized ionic liquid: DFT investigation, biological applications and electrochemical behavior of complexes

Mononuclear transition metal complexes based on ionic liquid have been prepared and characterized in detail. The biological properties of the three complexes were evaluated using radical scavenging activity, reducing power, antibacterial effect, DNA binding and cleavage activity. Among the complexes, [3-[(2R)-2-({[dichloro(η6-benzene)ruthenium]diphenylphosphanyl}oxy)-2-phenylethyl]-1-methyl-1H-imidazol-3-ium chloride] (4), demonstrated the highest radical scavenging (64.7 %) and reducing power activity (0.467) at 200 μg/ml concentration. The highest zone of inhibition was obtained from [3-[(2R)-2-({[dichloro(η6-p-cymene)ruthenium]diphenyl phosphanyl}oxy)-2-phenylethyl]-1-methyl-1H-imidazol-3-ium chloride] (3), against Bacillus cereus as 14 mm. Furthermore, all complexes were determined to have DNA binding and cleavage activities. Furthermore, theoretical DFT computations have also been carried out for the cationic complexes, to obtain minimum energy configuration of molecules. The effects of the chemical structures of three cationic complexes were also examined in relation to the variable property of electron-donating ligands for ruthenium-based complexes and iridium complex and their potential energy levels in ground and excited states HOMO and LUMO were determined.

Synthesis and thermal degradation mechanism of a semi-aromatic copolyamide from renewable sources

Bio-based polyamide has attracted increasing attention in recent years. However, it remains a challenge to synthesize bio-based polyamide combining excellent high temperature resistance and mechanical properties. And the thermal degradation mechanism of pentamethylenediamine-based semi-aromatic polyamide has not been reported. In this work, a semi-aromatic bio-based polyamide (PA5T/56) with high melting point, excellent mechanical properties, and high temperature resistance comparable to petroleum-based polyamide (PA6T/66) was successfully synthesized. The thermal degradation behaviors of PA5T/56 and PA6T/66 were characterized via TG-FTIR-MS and Py/ GC–MS, and the possible thermal degradation mechanisms were proposed. Different from PA6T/66, unique pyridines were traced in the degradation volatiles of PA5T/56 because of the cyclization tendency of the pentamethylenediamine structural unit. Moreover, the thermal degradation mechanism of PA5T/56 was mainly dominated by cleavage-cyclization of C–N bond accompanied by high-temperature radical cleavage reaction. This work will provide theoretical and practical basis for the design of bio-based high temperature resistant polyamide.

Nickel-Catalyzed Reductive Coupling of γ-Metalated Ketones with Unactivated Alkyl Bromides.

A nickel-catalyzed reductive cross-coupling reaction of aryl cyclopropyl ketones with easily accessible unactivated alkyl bromides to access aryl alkyl ketones has been developed. This strategy facilitates access to various of γ-alkyl-substituted ketones via ring opening of cyclopropyl ketones (26 examples, 50-90% yield). Initial mechanistic studies revealed that the reaction proceeds via radical cleavage of the alkyl bromide.

Functional role and ribosomal position of the unique N-terminal region of DHX29, a factor required for initiation on structured mammalian mRNAs.

Translation initiation on structured mammalian mRNAs requires DHX29, a DExH protein that comprises a unique 534-aa-long N-terminal region (NTR) and a common catalytic DExH core. DHX29 binds to 40S subunits and possesses 40S-stimulated NTPase activity essential for its function. In the cryo-EM structure of DHX29-bound 43S preinitiation complexes, the main DHX29 density resides around the tip of helix 16 of 18S rRNA, from which it extends through a linker to the subunit interface forming an intersubunit domain next to the eIF1A binding site. Although a DExH core model can be fitted to the main density, the correlation between the remaining density and the NTR is unknown. Here, we present a model of 40S-bound DHX29, supported by directed hydroxyl radical cleavage data, showing that the intersubunit domain comprises a dsRNA-binding domain (dsRBD, aa 377–448) whereas linker corresponds to the long α-helix (aa 460–512) that follows the dsRBD. We also demonstrate that the N-terminal α-helix and the following UBA-like domain form a four-helix bundle (aa 90–166) that constitutes a previously unassigned section of the main density and resides between DHX29’s C-terminal α-helix and the linker. In vitro reconstitution experiments revealed the critical and specific roles of these NTR elements for DHX29’s function.

Electrochemical oxygen reduction reaction at conductive polymer PEDOT: Insight from ab initio molecular dynamics simulations

Conducting polymers such as poly (3,4-ethylenedioxythiophene) (PEDOT) have attracted research attention as promising effective electrocatalytic materials for Oxygen Reduction Reaction (ORR). However, the complete reaction pathways leading to the hydrogen peroxide, H2O2, formation still remained unexplored. In this study, ab initio Born–Oppenheimer molecular dynamics (MD) calculations with an explicit solvent, were carried out to investigate the detailed mechanisms of the ORR on PEDOT via monitoring MD trajectories and analysing electronic energies. We confirm the outer-sphere nature of the first electron transfer and describe the essentially concerted electron–proton transfer nature of both oxygen reduction steps. Proton transfer is found to be involved in the first and second reduction steps and the role of water as an explicit solvent is outlined. Formation of the hydrogen peroxide is observed via either the reduction of hydroperoxyl radical HO2 or cleavage of its peroxo-adduct with PEDOT. It is therefore theoretically validated that the O2 reduction on a PEDOT may proceed a series pathway occurring simultaneously in acidic media. This approach provides an efficient and reliable means to rationalize and predict reaction mechanisms in solvent environment.

Quantum Chemical Study of a Radical Relay Mechanism for the HydG-Catalyzed Synthesis of a Fe(II)(CO)2(CN)cysteine Precursor to the H-Cluster of [FeFe] Hydrogenase.

The [FeFe] hydrogenase catalyzes the redox interconversion of protons and H2 with a Fe-S "H-cluster" employing CO, CN, and azadithiolate ligands to two Fe centers. The biosynthesis of the H-cluster is a highly interesting reaction carried out by a set of Fe-S maturase enzymes called HydE, HydF, and HydG. HydG, a member of the radical S-adenosylmethionine (rSAM) family, converts tyrosine, cysteine, and Fe(II) into an organometallic Fe(II)(CO)2(CN)cysteine "synthon", which serves as the substrate for HydE. Although key aspects of the HydG mechanism have been experimentally determined via isotope-sensitive spectroscopic methods, other important mechanistic questions have eluded experimental determination. Here, we use computational quantum chemistry to refine the mechanism of the HydG catalytic reaction. We utilize quantum mechanics/molecular mechanics simulations to investigate the reactions at the canonical Fe-S cluster, where a radical cleavage of the tyrosine substrate takes place and proceeds through a relay of radical intermediates to form HCN and a COO•- radical anion. We then carry out a broken-symmetry density functional theory study of the reactions at the unusual five-iron auxiliary Fe-S cluster, where two equivalents of CN- and COOH• coordinate to the fifth "dangler iron" in a series of substitution and redox reactions that yield the synthon as the final product for further processing by HydE.

Controllable synthesis of benzoxazinones and 2-hydroxy-3-indolinones by visible-light-promoted 5-endo-dig N-radical cyclization cascade

In recent years, significant advances have been made on photoredox-catalyzed N-radical addition to C-C unsaturated bond via N-H bond cleavage. However, these N-centered radical additions have so far been mostly limited to the alkenes, and to our knowledge, N-radical 5-endo-dig cyclizations of alkynes have been less exploited. Herein, we disclose an 5-endo-dig N-radical cascade cyclization of o-ethynylacetamides by photoredox catalysis involving rare radical cleavage of C-C triple bond, allowing the practical and controllable synthesis of a diverse array of valuable benzoxazinones and 2-hydroxy-3-indolinones in moderate to good yields under mild conditions. Furthermore, a mechanistic rationale for this radical cyclization cascade is supported by various control experiments and theoretical calculations.