Radical Formation Research Articles

Leveraging Propargyl Sulfides as Radical Trappers for the Synthesis of Sulfonyl Allenes

This work showcases a novel visible‐light mediated allenylation protocol employing propargyl sulfides as a pioneering radical trapping methodology. A diverse array of substituted sulfonyl allenes were successfully synthesized under mild conditions with commendable levels of chemo‐ and regio‐selectivity. Mechanistically, this process entails the formation of sulfonyl radicals, their subsequent addition to alkynes, the subsequent elimination of S‐centered radicals, and Cl‐atom abstraction, thereby facilitating the propagation of this radical chain reaction.

Mediating Spaces: The Scales of Yugoslav Socialist Thought

Beginning with its emergence in the 1870s and carrying through to the wars of the 1990s, Yugoslav socialism was animated by various visions of supranational affiliation: from Balkan federalism to communist Slavism to the nonaligned movement and European unification. These projects were examples of what this article terms mediating spaces: strategies of spatial consolidation designed to mediate their constituent nations’ integration into global capitalist modernity. Throughout the long twentieth century intellectuals on the world periphery set out to secure political sovereignty and economic development at a scale between the national and the global. These spatial projects were particularly pronounced in Yugoslavia, where the fragmentation of multiethnic empires made questions of supranational unity especially urgent. Developing the concept of mediating spaces, this article proposes a mode of intellectual history that approaches the global not as the scope of intellectual mobility or the horizon of historical inquiry, but rather as a generative scale of human experience that conditioned the formation of modern radical thought.

Reversal of the Regioselectivity of Iron‐Promoted Hydrogenation and Hydrohalogenation of gem‐Difluoroalkenes

AbstractThe reaction regioselectivity of gem‐difluoroalkenes is dependent on the intrinsic polarity. Thus, the reversal of the regioselectivity of the addition reaction of gem‐difluoroalkenes remains a formidable challenge. Herein, we described an unprecedented reversal of regioselectivity of hydrogen atom transfer (HAT) to gem‐difluoroalkenes triggered by Fe−H species for the formation of difluoroalkyl radicals. Hydrogenation of the in situ generated radicals gave difluoromethylated products. Mechanism experiments and theoretical studies revealed that the kinetic effect of the irreversible HAT process resulted in the reversal of the regioselectivity of this scenario, leading to the formation of a less stable α‐difluoroalkyl radical regioisomer. On basis of this new reaction of gem‐difluoroalkene, the iron‐promoted hydrohalogenation of gem‐difluoroalkenes for the efficient synthesis of aliphatic chlorodifluoromethyl‐, bromodifluoromethyl‐ and iododifluoromethyl‐containing compounds was developed. Particularly, this novel hydrohalogenation of gem‐difluoroalkenes provided an effect and large‐scale access to various iododifluoromethylated compounds of high value for synthetic application.

Asymmetric Three-Component Radical Alkene Carboazidation by Direct Activation of Aliphatic C-H Bonds.

Azide compounds are widely present in natural products and drug molecules, and their easy-to-transform characteristics make them widely used in the field of organic synthesis. The merging of transition-metal catalysis with radical chemistry offers a versatile platform for radical carboazidation of alkenes, allowing the rapid assembly of highly functionalized organic azides. However, the direct use of readily available hydrocarbon feedstocks as sp3-hybridized carbon radical precursors to participate in catalytic enantioselective carboazidation of alkenes remains a significant challenge that has yet to be addressed. Herein, we describe an iron-catalyzed asymmetric three-component radical carboazidation of electron-deficient alkenes by direct activation of aliphatic C-H bonds. This approach involves intermolecular hydrogen atom transfer between a hydrocarbon and an alkoxy/aryl carboxyl radical, leading to the formation of a carbon-centered radical. The resulting radical then reacts with electron-deficient alkenes to generate a new radical species that undergoes chiral iron-complex-mediated C-N3 bond coupling. An array of valuable chiral azides bearing a quaternary stereocenter were directly accessed from widely available chemical feedstocks, and their synthetic potential is further demonstrated through more facile transformations to give other valuable enantioenriched building blocks.

Electrocatalytic dehydrogenative and defluorinative coupling between aldehyde-derived N,N-dialkylhydrazones and fluoromalonates: synthesis of 2-pyrazolines.

An electrocatalytic synthesis of 2-pyrazolines via dehydrogenative and defluorinative cross-coupling reactions between (hetero)arylaldehyde-derived N,N-dialkylhydrazones and fluoromalonates is disclosed. Salient features of this work include (i) readily available starting materials, (ii) practical reaction conditions, and (ii) a formal oxidative (4 + 1)-cycloaddition via triple C-H bond functionalization. Cyclic voltammetry analyses support the electrocatalytic formation of an α-fluoromalonyl radical.

Parfitian or Buddhist reductionism? Revisiting a debate about personal identity

Derek Parfit influentially defends reductionism about persons, the view that a person’s existence just consists in the existence of a brain and body and the occurrence of a series of physical and mental events. Yet some critics, particularly Mark Johnston, have raised powerful objections to Parfit’s reductionism. In this paper, I defend reductionism against Johnston. In particular, I defend a radical form of reductionism that Buddhist philosophers developed. Buddhist reductionism can justify key features of Parfit’s position, such as the claims that personal identity is not what matters and can also be indeterminate. Furthermore, Buddhist reductionism can avoid Johnston’s objections to Parfit’s reductionism. I conclude that reductionists have good reasons to favor Buddhist reductionism over Parfit’s version.

Synergistic Photoenzymatic Catalysis Enables Synthesis of a-Tertiary Amino Acids Using Threonine Aldolases.

a-Tertiary amino acids are essential components of drugs and agrochemicals, yet traditional syntheses are step-intensive and provide access to a limited range of structures with varying levels of enantioselectivity. Here, we report the α-alkylation of unprotected alanine and glycine by pyridinium salts using pyridoxal (PLP)-dependent threonine aldolases with a Rose Bengal photoredox catalyst. The strategy efficiently prepares various a-tertiary amino acids in a single chemical step as a single enantiomer. UV-vis spectroscopy studies reveal a ternary interaction between the pyridinium salt, protein, and photocatalyst, which we hypothesize is responsible for localizing radical formation to the active site. This method highlights the opportunity for combining photoredox catalysts with enzymes to reveal new catalytic functions for known enzymes.

Boron Cluster Renders Organic Radicals Water-Stable for Photothermal Anti-Infections.

Water-stable organic radicals are promising photothermal conversion candidates for photothermal therapy (PTT). However, organic radicals are usually unstable in biological environments, which greatly hinders their wide application. Here, we have developed a chaotropic effect-based and photoinduced water-stable supramolecular radical (MB12-2) for efficient antibacterial PTT. The supramolecular radical precursor MB12-1 was constructed by the chaotropic effect between closo-dodecaborate cluster (B12H122-) and N,N'-dimethylated dipyridinium thiazolo [5,4-d] thiazole (MPT2+). Subsequently, with triethanolamine (TEOA) serving as an electron donor, MB12-1 could transform to its radical form MB12-2 through photoinduced electron transfer (PET) under 435-nm laser irradiation. The N2 adsorption-desorption analysis confirmed that MB12-2 was tightly packed through the introduction of B12H122-, which effectively enhanced its stability via a spatial site-blocked effect. Moreover, the half-life of MB12-2 in water was calculated through ultraviolet-visible light (UV-vis) absorption spectra results for periods as long as 20 days. In addition, in the skin infection model, MB12-2, as a wound dressing, showed remarkable photothermal antibacterial activity (>97%) under 660-nm laser irradiation and promoted wound healing. This study presents a simple method for designing long-term water-stable supramolecular radicals, offering a novel avenue for noncontact treatments for bacterial infections.

Mutational dissection of a hole hopping route in a lytic polysaccharide monooxygenase (LPMO)

Oxidoreductases have evolved tyrosine/tryptophan pathways that channel highly oxidizing holes away from the active site to avoid damage. Here we dissect such a pathway in a bacterial LPMO, member of a widespread family of C-H bond activating enzymes with outstanding industrial potential. We show that a strictly conserved tryptophan is critical for radical formation and hole transference and that holes traverse the protein to reach a tyrosine-histidine pair in the protein’s surface. Real-time monitoring of radical formation reveals a clear correlation between the efficiency of hole transference and enzyme performance under oxidative stress. Residues involved in this pathway vary considerably between natural LPMOs, which could reflect adaptation to different ecological niches. Importantly, we show that enzyme activity is increased in a variant with slower radical transference, providing experimental evidence for a previously postulated trade-off between activity and redox robustness.

Electrochemically produced nano-TiO2-coated SiC membranes for photocatalytic water treatment: Preparation, characterization, and hydroxyl radical formation

ABSTRACT Photocatalytically active ceramic flat sheet membranes based on a nanostructured titanium dioxide (TiO2) coating were produced for photocatalytic water treatment. The nano-TiO2 layer was produced by a novel combination of magnetron sputtering of a thin titanium layer on silicon carbide (SiC) membranes, followed by electrochemical oxidation (anodization) and subsequent heat treatment. Characterization by Raman spectra and field emission scanning electron microscopy proved the presence of a nanostructured anatase layer on the membranes. The influence of the titanium layer thickness on the TiO2 formation process and the photocatalytic properties were investigated using anodization curves, by using cyclovoltammetry measurements, and by quantifying the generated hydroxyl radicals (OH•) under UV-A irradiation in water. Promising photocatalytic activity and permeability of the nano-TiO2-coated membranes could be demonstrated. A titanium layer of at least 2 μm was necessary for significant photocatalytic effects. The membrane sample with a 10 μm Ti/TiO2 layer had the highest photocatalytic activity showing a formation rate of 1.26 × 10−6 mmol OH• s−1. Furthermore, the membranes were tested several times, and a decrease in radical formation was observed. Assuming that these can be attributed to adsorption processes of the reactants on the TiO2 surface, initial experiments were carried out to reactivate the photocatalyzer.

Iodine-promoted amide formation via oxidative cleavage of indoles: novel quinazoline-4(3H)-one and tryptanthrin syntheses.

A highly efficient method for the direct construction of amide bonds via a selective cleavage of C-H and C[double bond, length as m-dash]C bonds in indole structures using an iodine-promoted approach was developed. Mechanistic studies indicated the formation of superoxide radicals obtained from molecular oxygen activation as a key intermediate step, which provided a precursor for subsequent oxidative ring-opening and intermolecular cyclization. A broad range of quinazolin-4(3H)-ones and tryptanthrins were synthesized in moderate to good yields under mild and environmentally benign conditions.

Correction of Nitrosative Stress During Reparative Regeneration of the Nasal Cavity Mucosa in an Experimental

Introduction. Nitric oxide metabolites play an important role in prolongation of the inflammatory reaction, disorders of epithelial regeneration in diseases of the upper respiratory tract. One of the promising approaches to regulating the bioactivity of nitric oxide is the use of antioxidants.The objective of the study is to evaluate the effectiveness of antioxidant therapy for the correction of nitrosative stress during reparative regeneration of the nasal mucosa in an experiment.Methods. A preclinical randomized experimental study is conducted on 160 rats, divided into 4 groups. The control group (n = 40) consists of intact animals. Animals in experimental group 1 (n = 40) do not receive treatment aſter injury; in group 2 (n = 40) anti-inflammatory treatment is prescribed. The third group consists of laboratory rats (n = 40), which are additionally injected into the nasal cavity with an antioxidant — a 15 % solution of 1,1-dimethyl-3-oxobutylphosphonic acid dimethyl ester. On days 2, 5, 10, and 14 of observation, the concentration of nitrates and nitrites and C-reactive protein in the blood of animals are determined.Results. In group 3, aſter an increase in the level of nitric oxide metabolites on day 2 aſter injury on day 5, a significant (p < 0.05) decrease was noted in comparison with other groups, and by day 10— normalization of the indicator. An increase in the level of C-reactive protein in blood serum correlated with the concentration of nitric oxide metabolites.Discussion. The optimal therapeutic effect when taking antioxidants develops when administered in the first hours aſter injury to reduce the excessive formation of reactive nitrogen radicals. However, the duration of administration should not exceed 4–5 days to avoid a significant decrease in the level of nitric oxide metabolites and deterioration of mucosal regeneration.Conclusions. Assessment of nitric oxide metabolitesin the blood at different times aſter injury is an important marker of inflammatory activity. The use of antioxidants helps to reduce the concentration of active nitrogen radicals.

Kinetic Computation of Cyclization Reactions of Large Keto-Hydroperoxide Radicals in Low Temperature Combustion.

The cyclization reactions of keto-hydroperoxide (KHP) radicals leading to the formation of keto cyclic ethers and OH radicals play an important role in low temperature combustion for hydrocarbon fuels or oxygenated hydrocarbon fuels. However, due to the lack of kinetic data of cyclization reactions of KHP radicals, researchers often derive high-pressure-limit rate constants of cyclization reactions of KHP radicals from analogous cyclization reactions of hydroperoxyl alkyl radicals during construction of the combustion mechanism. This study aims to systematically investigate the kinetics of cyclization reactions of KHP radicals involving short-to-large-sized radicals. The studied reactions are divided into 7 reaction classes, according to the size of the cyclic transition state, the conjugative effect (whether KHP radicals are resonance-stabilized or not), and the position of the carbonyl group (whether the carbonyl group is inside or outside of the reaction center). The isodesmic reaction method, in conjunction with transition state theory, is utilized for each reaction class to compute the energy barriers and high-pressure-limit rate constants at the DFT level. The study revealed that energy barriers calculated at the DFT level with correction by the isodesmic reaction method are close to the results from the benchmark CCSD(T) method. To develop more accurate rate rules, these reaction classes are further divided into subclasses based on the relative site of the OOH group with the carbonyl group, the type of carbon atoms where the OOH group is located, and the type of carbon atoms where the radical site is located. For each subclass, high-pressure-limit rate rules are derived by averaging the rate constants of reactions in the subclass, and it is found that the maximum absolute deviation of the energy barrier and the ratio of the largest rate constant to the smallest rate constant among reactions in each subclass are within chemical accuracy limits, indicating acceptable use of the developed rate rules. A comparison of the rate constants for cyclization reactions of KHP radicals with the values of analogous cyclization reactions of hydroperoxyalkyl radicals as provided in reported mechanisms is made. Additionally, a comparison is drawn between our developed rate rules for subclasses of the cyclization reactions of KHP radicals and the rate rules for analogous subclasses of cyclization reactions of hydroperoxyl alkyl radicals. These comparisons demonstrate significant differences and highlight the necessity for improved rate rules for cyclization reactions of KHP radicals to enhance the automatically generated combustion mechanisms for hydrocarbon and oxygenated hydrocarbon fuels.

Direct Determination of Absolute Radical Quantum Yields in Hydroxyl and Sulfate Radical-Based Treatment Processes.

The absolute radical quantum yield () is a critical parameter to evaluate the efficiency of radical-based processes in engineered water treatment. However, measuring is fraught with challenges, as current quantification methods lack selectivity, specificity, and anti-interference capabilities, resulting in significant error propagation. Herein, we report a direct and reliable time-resolved technique to determine at pH 7.0 for commonly used radical precursors in advanced oxidation processes. For H2O2 and peroxydisulfate (PDS), the values of •OH and at 266 nm were measured to be 1.10 ± 0.01 and 1.46 ± 0.05, respectively. For peroxymonosulfate (PMS), we developed a new approach to determine with terephthalic acid as a trap-and-trigger probe in the nonsteady state system. For the first time, the value was measured to be 0.56 by the direct method, which is stoichiometrically equal to (0.57 ± 0.02). Additionally, radical formation mechanisms were elucidated by density functional theory (DFT) calculations. The theoretical results showed that the highest occupied molecular orbitals of the radical precursors are O-O antibonding orbitals, facilitating the destabilization of the peroxy bond for radical formation. Electronic structures of these precursors were compared, aiming to rationalize the tendency of the values we observed. Overall, this time-resolved technique with specific probes can be used as a reliable tool to determine , serving as a scientific basis for the accurate performance evaluation of diverse radical-based treatment processes.

Nickel-Photoredox-Catalyzed Stereoconvergent Coupling of Alkenyl Halides and Nitrogen-Containing Heterocycles.

Nitrogen-containing heterocycles possessing N-alkenyl substituents are an important structural motif. However, the synthetic methods reported thus far cannot selectively synthesize the Z stereoisomer on the basis of the stereochemistry of the substituted alkenes. Herein, we report the stereoconvergent coupling of heterocycles and alkenyl halides consisting of a mixture of E/Z stereoisomers, which selectively afforded the thermodynamically less stable Z-coupling product. Mechanistic studies suggest that a nickel photoredox catalyst facilitates the formation of N-centered heteroarene radicals.

Electrochemical strategies for determination of tert-butyl hydroquinone (TBHQ) in food samples

AbstractTert-butyl hydroquinone (TBHQ) is a member of the synthetic phenolic antioxidant family that prevents the formation of free radicals and prevents radicals from damaging cells by trapping them. In addition, TBHQ is widely preferred as an additive in foods and vegetable oils because of its low cost and high chemical stability. TBHQ is not only a food preservative but is also frequently used as a stabilizer to prevent auto-polymerization in cosmetics, biodiesel, pharmaceuticals, coating products, and different application areas. TBHQ has been shown to cause diseases, such as DNA damage, carcinogenesis, and cell apoptosis, when administered at high doses. Excessive consumption of TBHQ causes adverse effects, such as stomach tumors, liver damage, and underdevelopment of the reproductive system. Different analytical methods have been used to detect TBHQ in food samples. The most important of these methods are traditional analytical methods such as chromatographic and spectrophotometric methods. However, these methods have basic shortcomings such as high analysis costs, long pre-processing, expensive equipment, need for many organic solvents, requiring expertise, and long detection times. In recent years, electrochemical sensors have attracted attention in the scientific world owing to their high sensitivity, fast analysis time, portability, low cost, and convenience of miniaturization. This review discusses electrochemical studies performed to date for the determination of TBHQ in food samples. The methods used in these studies have been evaluated in a wide range of aspects, such as the electrode, working range, detection limits, and analytical applications.

Studies of the diluent, temperature and pressure effect on the lower and upper flammability limits of ammonia in air

Ammonia safety and environmental protection research forms the basis for its role as a clean energy carrier. In this work, an experimental study was conducted in this work to analyze the effect of different inhibitors (nitrogen, argon and water vapor) on the flammability limits (FLs) of ammonia at elevated temperatures and pressures. In addition, the influence of diluents on the compositions and flame temperature changes was evaluated, and the temperature sensitivity coefficients of the elementary reactions and the ROP of free radicals and partial products at the FL concentrations were analyzed. The findings indicated that water vapor provided the strongest flame retardant effect on ammonia in three inhibitors. Within a certain temperature and pressure range, the FLs of ammonia in ammonia/diluent/air can be predicted using the extended Le Chatelier equation. The flame temperature decreased at the lower flammability limit (LFL) concentrations and increased at the upper flammability limit (UFL) concentrations of ammonia with increasing initial pressure. As the initial temperature increases, the flame temperature decreases during ammonia combustion. The influence of ammonia concentration on flame temperature is greater than that of diluents dilution. The elementary reactions H+O2<=>O+OH (R1) and NH2+NO<=>NNH+OH (R82) were the primary reactions that increased the flame temperature at the FL ammonia concentrations in ammonia/diluent/air. Conversely, NH2+NO<=>N2+H2O (R80) and H+O2(+M)<=>HO2(+M)(R15) were the main reactions that decreased the flame temperature. H, OH and NH2 radicals played a crucial role in the combustion reaction process at ammonia FL concentrations. At the LFL concentrations of ammonia, the molar fraction of the OH radical showed the greatest variation, while at the UFL concentrations of ammonia it was NH2 radical. The elementary reaction NH3+OH<=>NH2+H2O (R158) was the primary reaction that consumed OH radical and promoted the formation of NH2 radical. Free radical concentrations decreased with increasing pressure and temperature, while the change rate of free radical ROP accelerated with increasing pressure. In addition to nitrogen and water, the partial products were mainly nitric oxide at the LFL concentrations, while at the UFL concentrations were mainly hydrogen.

Aminonaphthalene and aminoquinoline photocages: meta-effect and photo-release of carboxylic acids and alcohols

Three series of compounds were tested as photocleavable protective groups (photocages), which are derivatives of 1,2-substituted aminonaphthalene 4, 1,3-substituted aminonaphthalene 5, or 5,6-substituted aminoquinolines 6. Their photophysical properties and photochemical reactivity in releasing alcohols and carboxylic acids were investigated. Moreover, mechanism of photochemical reaction was studied computationally and by transient absorption spectroscopy with time-resolution from femtoseconds to milliseconds. Photocages 4 and 5 are generally fluorescent molecules with high ΦF, whereas quinoline 6 is weekly fluorescent due to photoinduced charge transfer. Derivatives 4 release alcohol with low quantum yield (release of methanol from 4d is ΦR = 0.00010 ± 0.00005), but upon prolonged irradiation can be applied in organic synthesis to deprotect both aliphatic and aromatic alcohols. On the contrary, photocages 5 undergo relatively efficient release of carboxylic acids, (release of acetic acid from 5b is ΦR = 0.22 ± 0.01), in accord with the meta-effect in photochemistry, which is our main discovery that is based on the rational design of the chromophore. The photochemical reaction mechanism involves homolytic cleavage on the singlet excited state surface and formation of radicals which were detected by transient spectroscopy. The meta-effect did not promote the heterolytic cleavage as it was the case with aniline chromophores. The subsequent electron transfer delivers naphthalenmethyl carbocation and released carboxylates. The applicability of photocages 5 in organic synthesis was demonstrated on aliphatic and aromatic carboxylic acids. The potential use in biology was suggested due to their very weak photoinduced antiproliferative effect, which was essayed on three human cancer cell lines (MCF-7 breast carcinoma, HCT 116 colon carcinoma, and H460 lung carcinoma).

Photoelectrochemical Conversion of Methane to Ethane and Hydrogen under Visible Light Using Functionalized Tungsten Trioxide Photoanodes with Proton Exchange Membrane.

Developing methane utilization technologies is desired to convert abundant and renewable carbon resources, such as natural gas and biogas, into value-added chemical products. This study provides insights into emerging photoelectrochemical (PEC) technology for the photocatalytic transformation of methane to C2H6 and H2 using visible light at room temperature. The PEC conversion of methane to oxygenates has been investigated in aqueous electrolytes. Herein, we demonstrate the gas-phase PEC methane conversion using a proton exchange membrane (PEM) as a solid polymer electrolyte and a gas-diffusion photoanode for methane oxidation. Tungsten trioxide (WO3), a semiconductor photocatalyst responsive to visible light, is utilized as the photoanode material. Ultraviolet light (∼365 nm) excitation predominantly results in CO2 production with lower C2H6 selectivity in humidified methane. In contrast, visible light (∼453 nm) effectively promotes C2H6 production over the WO3 photoanode, attributed to preferential hydroxyl radical (•OH) formation compared to UV irradiation. Photogenerated holes formed near the valence band maximum of WO3 contribute to •OH formation through a single-electron water oxidation. The photogenerated •OH activates gaseous methane molecules to methyl radicals, subsequently coupled into C2H6 at the gas-electrolyte-semiconductor boundary. H2 is concurrently formed on the cathode electrocatalyst. Improving the selectivity for the dehydrogenative coupling of methane is pivotal for enhancing the energy efficiency in the PEM-PEC system.

Effect of deodorization conditions on fatty acid profile, oxidation products, and lipid-derived free radicals of soybean oil

Oxidative stability is a key quality characteristic of edible oils, and the oil’s antioxidant capacity decreases during the deodorization stage. This study explores the changes in radical formation, molecular structure, oxidative characteristics, fatty acids, and main bioactive compounds in soybean oil during deodorization. The lag phase decreased, whereas the total amount of spins of free radicals increased as the deodorization time increased from 90 to 150min. The total amount of spins and percentage of alkyl radicals varied dramatically under different times and temperatures (220 ∼ 260 ℃). Results showed that identifying and quantifying the formed radicals can provide useful information for monitoring and controlling oil oxidation in vegetable oil refining systems. Therefore, to control early oxidation events, maximize refined oil product yield, and reduce energy consumption in the refining plant, the priority should be to minimize temperature during the oil refining process and then shorten the deodorization time.