Radical Formation Research Articles

Synthesis of 1‐Azabicyclo[2.1.1]hexanes via Formal Single Electron Reduction of Azabicyclo[1.1.0]butanes under Photochemical Conditions

AbstractC(sp3)‐rich heterocycles are privileged building blocks for pharmaceuticals and agrochemicals. Therefore, synthetic methods that provide access to novel saturated nitrogen‐containing heterocycles are in high demand. Herein, we report a general synthesis of 1‐azabicyclo[2.1.1]hexanes (1‐aza‐BCH) via a formal cycloaddition of azabicyclo[1.1.0]butanes (ABB) with styrenes under photochemical conditions. To overcome the challenging direct single electron reduction of ABBs, we designed a polar‐radical‐polar relay strategy that leverages a fast acid‐mediated ring‐opening of ABBs to form bromoazetidines, which undergo efficient debrominative radical formation to initiate the cycloaddition reaction. The reaction is applicable to a broad range of ABB‐ketones and we demonstrate the 1‐aza‐BCH products can be further functionalized to access larger saturated, conformationally rigid heterocycles.

Synthesis of 1-azabicyclo[2.1.1]hexanes via formal single electron reduction of azabicyclo[1.1.0]butanes under photochemical conditions.

C(sp3)-rich heterocycles are privileged building blocks for pharmaceuticals and agrochemicals. Therefore, synthetic methods that provide access to novel saturated nitrogen-containing heterocycles are in high demand. Herein, we report a general synthesis of 1-azabicyclo[2.1.1]hexanes (1-aza-BCH) via a formal cycloaddition of azabicyclo[1.1.0]butanes (ABB) with styrenes under photochemical conditions. To overcome the challenging direct single electron reduction of ABBs, we designed a polar-radical-polar relay strategy that leverages a fast acid-mediated ring-opening of ABBs to form bromoazetidines, which undergo efficient debrominative radical formation to initiate the cycloaddition reaction. The reaction is applicable to a broad range of ABB-ketones and we demonstrate the 1-aza-BCH products can be further functionalised to access larger saturated, conformationally rigid heterocycles.

Thiamine Deficiency and its Implications on Microvascular Complications of Diabetes Mellitus

Thiamine is the first vitamin discovered and belongs to Vit B family. The main effect seen with thiamine deficiency is Beri-Beri, Wernicke’s encephalopathy, Wernicke-Korsak off syndrome and are considered as a serious condition but often can be reversed. The deficient status of thiamine can also cause varied affects and can overlap with other conditions to exacerbate its potent effects. It is seen that thiamine is necessary for the metabolism of glucose in the form of cofactors, deficiency of which leads to accumulation of toxic glucose metabolites leading to formation of free radicals and oxidative stress. Glucose is not only important for the formation of energy but its improper metabolism proves to have deleterious effects in the body. In this review, an attempt is made to correlate microvascular complications of diabetes with thiamine deficiency and can be discerned that oxidative stress is one of the important factors for the progress of microvascular complications, as well as diabetic ketoacidosis, atherosclerosis and cardiovascular damage in patients with diabetes mellitus and these can be prevented or maintained by optimizing thiamine levels in the body.

New spacious SrWO4/PEDOT-PPy nanohybrids and their electrochemical and photocatalytic activities.

A novel SrWO4-poly(3,4-ethylene dioxythiophene) (PEDOT)-polypyrrole (PPy) nanocomposite was synthesized via chemically oxidative polymerization and considered by using numerous method of the techniques. The resulting SrWO4/PEDOT-PPy nanocomposite demonstrated remarkable electrochemical sensing capabilities for sulfadiazine (SFA). As a modified glassy carbon electrode (SrWO4/PEDOT-PPy/GCE) revealed for superior catalytic activity in the electrochemical oxidation of sulfadiazine, enabling sensitive detection with quantification and detection limits of 1.0936 × 10-9M µA-1 and 2.2104 × 10-9M µA-1, respectively. This technique effectively determined SFA content in real samples. Additionally, SrWO4/PEDOT-PPy demonstrated extraordinary photocatalytic ability, achieving a Methylene Blue (MB) degradation rate of up to 99.1% under halogen light irradiation within 80min. Hybrid photocatalyst has exhibited to strong reusability and photocatalytic stability under frequent light exposure. A contrivance for the photocatalytic deprivation of MB by SrWO4/PEDOT-PPy is proposed. These results underscore the crucial role of SrWO4/PEDOT-PPy in practical environmental remediation analysis. The fluorescence investigations have betrothed to terephthalic acid radical formations of SrWO4/PEDOT-PPy hybrids, which were modulated by different approaches, and its mainly driven for higher illumination aptitudes. Meanwhile, this was more supporting for physio-chemical properties of the phenomenon, at this consequential with significantly well improved to the photocatalytic performances. Because of this, SrWO4/PEDOT-PPy hybrid materials were comprehended to deliver excellent kinetics, and better recyclable activities.

Hydrothermal growth of Zn2GeO4 nanorods for optical and (Photo)Catalytic applications: An experimental and theoretical study

From the material design perspective, we reported a systematic investigation based on theoretical and experimental approaches to explore the physical properties of Zn2GeO4 nanorods prepared by hydrothermal method with different zinc precursors for optical and (photo)catalytic applications. All ZGO samples exhibited uniform nanorod morphology with high purity and crystallinity. A negative zeta potential ranging from −13 mV to −16 mV have been observed for these nanorods. Bandgap values indicated variations among samples synthesized with different precursors. The photoluminescence and photocatalytic activities for these nanorods, have been attributed to the presence of oxygen vacancies on the Zn2GeO4 surfaces. Experimental evidence suggests that these surface defects favor the formation of hydroxyl radicals identified as primary reactive oxygen species responsible for the methylene blue photodegradation. Toxicity testing of photocatalytic residues showed minimal phytotoxic effect on lettuce seed (Lactuca sativa) germination. Additionally, Zn2GeO4 was utilized as an acid catalyst for synthesizing isoxazol-5(4H)-ones, resulting in an increase in the yield from 69 % to 92 % by using this catalyst in multicomponent reactions. Lastly, the theoretical efforts outlined in the study aim to enhance the comprehension of the material design with well-defined morphology using realist theoretical models for the Zn2GeO4 nanorods for the first time.

A General Copper-Box System for the Asymmetric Arylative Functionalization of Benzylic, Propargylic or Allenylic Radicals.

Radical-involved arylative cross-coupling reactions have recently emerged as an attractive strategy to access valuable aryl-substituted motifs. However, there still exist several challenges such as limited scope of radical precursors/acceptors, and lack of general asymmetric catalytic systems, especially regarding the multicomponent variants. Herein, we reported a general copper-Box system for asymmetric three-component arylative radical cross-coupling of vinylarenes and 1,3-enynes, with oxime carbonates and aryl boronic acids. The reactions proceed under practical conditions in the absence or presence of visible-light irradiation, affording chiral 1,1-diarylalkanes, benzylic alkynes and allenes with good enantioselectivities. Mechanistic studies imply that the copper/Box complexes play a dual role in both radical generation and ensuing asymmetric cross-coupling. In the cases of 1,3-enynes, visible-light irradiation could improve the activity of copper/Box complex toward the initial radical generation, enabling better efficiency match between radical formation and cross-coupling.

Engineering Thermally Reduced Graphene Oxide for Synchronously Enhancing Photocatalytic Activity and Photothermal Effect.

The structural composition of reduced graphene oxide (rGO) can be modified and controlled by appropriate reduction methods to modulate its electronic structure, rendering it a versatile platform for tailoring optoelectronic and catalytic properties. Nevertheless, it is uncommon to concurrently amplify the photocatalytic and photothermal effects when regulating and utilizing pure rGO. Here, we investigate the impact of structural variations in thermally reduced graphene oxide (TGO) on its photocatalytic and photothermal properties. Various characterization results demonstrate that appropriate thermal reduction facilitates the preservation and transformation of oxygenated groups and structure defects, which in turn encourages the formation of reactive carbon radicals and discrete graphitic domains, thereby strengthening the activation of molecular oxygen and the plasmonic photothermal effect under near-infrared (NIR) light irradiation. Moreover, the optimized TGOs exhibit efficient sterilization with NIR irradiation due to enhanced photocatalytic activities and photothermal effects. This work highlights the potential for developing photocatalytic and photothermal rGO-based materials through structural engineering.

Photochemical coupling reaction of phenacyl benzoate with acetone to form 1,4‐dicarbonyl compound enabled by charge transfer

AbstractPhotolysis of phenacyl benzoates tethered with a phenol or anisole in acetone resulted in the formation of 1,4‐dicarbonyl compounds, coupling products of the phenacyl moiety with acetone. The reaction occurs via electron and/or proton transfer from a triplet exciplex, leading to the formation of a phenacyl radical, which then adds to the enol form of acetone. The reaction also occurs in intermolecular fashion with external electron donors.

Unveiling chlorine's role: How it shapes the formation and light-activated oxygen dynamics of chlorophenol-derived environmental persistent free radicals

Environmental persistent free radicals (EPFRs) derived from chlorophenols, triggered by light or heat exposure, pose significant ecological concerns, yet the impact of chlorine substituents on EPFRs formation and reactivity remains inadequately understood. Through an intentional synthesis of chlorophenol-derived EPFRs with varying chlorine contents and positioning, we elucidated the role of chlorine in the photoactivation of molecular oxygen. Our combined experimental and theoretical analysis reveals that these EPFRs are primarily oxygen-centered phenoxy radicals, establishing a direct link between chlorine substitution patterns and their ability to activate molecular oxygen under visible light. Increased chlorine content enhances EPFRs formation by elevating the positive charge on the phenolic hydroxyl group’s hydrogen atom, facilitating its removal. Moreover, the capability of EPFRs to activate molecular oxygen was directly correlated with chlorine content, with 2,3,5,6-tetrachlorophenol-derived EPFRs showcasing the highest activity. This activity is attributed to their structural propensity for TCSQ·- species generation. Furthermore, our study established a significant correlation between the toxicity and activity of EPFRs, emphasizing the critical role of halogen substituents in determining the reactivity of EPFRs. These insights contribute to our understanding of their environmental and toxicological ramifications, underscoring the imperative for continued research aimed at mitigating their detrimental impacts.

Silyl Radicals as Single-Electron Reductants: α-Aminoalkyl Radical Formation via a Photocatalytic Oxidatively Initiated Radical Chain Process.

The α-amino-radical constitutes a versatile reactive intermediate that has been used to great effect in the synthesis of complex amine-containing products. Here, we report the development of a multicomponent photocatalytic platform enabling access to all-alkyl α-amino-radicals, exploiting the oxidative formation of silyl-radicals from commercially available tris(trimethylsilyl)silane. A key design element of the new process involves the role of silyl-radicals in generating α-amino-radicals from iminium ions as part of an oxidatively initiated photocatalytic radical chain process. This distinct activation mode is showcased by engaging the ensuing radicals in cross-radical coupling with persistent arene radical anions, enabling the arylation of in situ-generated all-alkyl iminium ions to furnish alkyl-substituted benzylamines.

Oxygen, the Paradox of Life and the Eye

Oxidative stress, caused by the formation of free radicals, such as reactive oxygen species (ROS), leads to cell and tissue degradation, contributing to various diseases and aging. While oxygen is essential for aerobic organisms, it inevitably causes oxidative stress. Antioxidants protect against damage from free radicals, and oxidative stress arises when an imbalance occurs between free radical production and antioxidant defenses. However, when investigating whether an excess of antioxidants, almost eliminating oxidative stress, could benefit aging and disease susceptibility, it was observed that a basic level of oxidative stress appears necessary to maintain the correct homeostasis of tissues and organs and life in general. Therefore, this review aimed to compile the most significant and recent papers characterizing and describing the dual role of oxygen as a molecule essential for life and as a precursor of oxidative stress, which can be detrimental to life. We conducted targeted searches in PubMed and Google browsers to gather all relevant papers. We then focused on the eye, an organ particularly vulnerable due to its high metabolic activity combined with direct exposure to light and environmental pollutants, which produces a substantial number of free radicals (mainly ROS). We present a curated selection of relevant literature describing the main ocular pathologies of the posterior and anterior segments of the eye, highlighting oxidative stress as a significant contributing factor. Additionally, we report how endogenous and exogenous antioxidants can mitigate the development and progression of these diseases. Finally, we consider a frequently overlooked aspect: the balance between oxidants and antioxidants in maintaining the homeostatic equilibrium of tissues and organs. It is widely recognized that when oxidants overwhelm antioxidants, oxidative stress occurs, leading to negative consequences for the organism's homeostasis. However, we emphasize that a similarly dangerous situation can arise when the presence of antioxidants overwhelms the production of free radicals, drastically reducing their amount and adversely affecting aging and longevity. Unfortunately, no specific studies have addressed this particular situation in the eye.

Theoretical–experimental evaluation of the effects of Fe3+ ions in the disinfection of water supply by peracetic acid

Peracetic acid (PAA) is efficient for disinfection processes in environmental sanitation and in the presence of transition metals its oxidative performance is enhanced. Thus, the present study aim evaluated the influence of Fe3+ ions during the inactivation process of Escherichia coli and Total Coliforms (TC). The process PAA + Fe3+ ions were also evaluated in relation to the disinfection kinetics, the participation of H2O2 and the influence of the organic load of the treated water. The tests showed an inactivation efficient of 0.5 to 0.9 log in relation to E. coli and 1.3 to 1.5 logs for TC in the concentrations evaluated and complete inactivation of E. coli was achieved within 15 min for both PAA and PAA/Fe3+ There is no damage to the disinfection process in the presence of Fe3+ ions, however, the decomposition of PAA is favored. In this sense, the formation of radicals can justify the maintenance of disinfection efficiency. The decay constants were close both microorganisms: for E. coli with PAA and PAA/Fe3+were 0.0323 and 0.0476 and for TC were 0.0637 and 0.0667. The values of R2 were above 0.95. Computer simulations of peptidoglycans that make up the bacterial cell wall showed that radicals preferentially attacked the carbons from the rings that composes the cell wall peptidoglycan of gram-negative bacteria allowing to break the structure during the disinfection process.

Atmospheric oxidation pathways of CF3CH2CFCl2 (HCFC-234fb) with OH-radicals and Cl-atoms: insights into the mechanism, thermodynamics, and kinetics.

The atmospheric oxidation of 1,1-dichloro-1,3,3,3-tetrafluoropropane, HCFC-234fb (DTP), leads to the formation of harmful radicals, contributing to stratospheric ozone depletion. Thus, a detailed study of the gas-phase oxidation of the first-generation chlorofluorocarbon alternative HCFC-234fb by a reaction with hydroxyl radicals and chlorine atoms is important to understand its harmful effects on the environment. In this work, we have performed quantum chemical calculations to investigate the thermodynamic and kinetic aspects of the titled reaction. The potential energy profile calculated at the CCSD(T)/aug-cc-pVTZ//MP2/cc-pVTZ level of theory shows that the major reaction pathway involves the abstraction of the H-atom from the central carbon atom, C2, giving rise to the product radical CF3C˙HCCl2F. The calculated rate-coefficients for the reaction with ˙OH and Cl-atoms are 3.89 × 10-15 and 2.54 × 10-17 cm3 molecule-1 s-1, respectively, at 298 K and are in accordance with the experimental rate coefficients. The results suggest that the rate-coefficient for the reaction of DTP with ˙OH is two orders of magnitude higher than that with Cl-atoms, indicating greater significance of the former reaction in the atmosphere. With the rate-coefficient values, the lifetime and the radiative efficiency were calculated to be 8.2 years and 0.246 W m-2 ppb-1, respectively. A 100-year global warming potential (GWP) of 712 was also estimated using the lifetime corrected radiative efficiency value.

Hydrazone-Linked Donor-Acceptor Covalent Organic Polymer as a Heterogeneous Photocatalyst for C-S Bond Formation.

In the realm of solar energy utilization, there is a growing focus on designing and implementing effective photocatalytic systems, for the conversion of solar energy into valuable chemical fuels. The potential of Covalent Organic Polymers (COPs) as photocatalysts for visible-light-driven organic transformation has been widely investigated, positioning them as promising candidates in this field. In the design of COPs, introducing a donor-acceptor arrangement facilitates the transfer of electrons from the donor to the acceptor, creating a charge transfer complex and leading to enhanced conductivity and improved charge separation. Here we present a novel hydrazone-linked covalent organic polymer ETBC-PyHz containing TPE donor and pyridine acceptor. Utilizing this, an efficient method has been developed for an oxidative cross-coupling reaction involving C-S bond formation. This process involves arylhydrazines and arenethiols, and results in the production of unsymmetrical diaryl sulfides via the formation of aryl and thioarene radicals. This conversion holds significant importance because the byproducts produced during the process are nitrogen and water, making it environmentally benign.

Vibrational Features of Oxyamines: A Comparative Study of N,N-Diethylhydroxylamine and N,N-Diethylacetyloxyamine.

The ability of oxyamines to undergo homolytic cleavage of the O-C bond, leading to the formation of stable radicals, is widely used in polymerization processes and to prevent oxidative stress in materials. We present a mid and near-infrared spectroscopy study on two model compounds, N,N-diethylhydroxyloxyamine (C4H11NO) and its acetyl derivative N,N-diethylacetyloxyamine (C6H13NO2) in the liquid phase. The analysis of the spectra is based on a complete exploration of the conformational space, coupled to harmonic and anharmonic calculations performed using the generalized second-order vibrational perturbation theory (GVPT2) formalism at the B3LYP-D3(BJ)/Def2-TZVP level of calculation and potential energy distribution analysis. In the most stable species out of 25, the three amine chains present an all-anti arrangement, with the carbonyl oxygen atom pointing towards the nitrogen lone pair. The simulated spectra are in overall good agreement with the experimental ones, and suitable for the assignment of the main observed bands. Furthermore, similarities and divergences between the two molecules are discussed.

Tunable and Photoactivatable Mimics of Calicheamicin γ1 for DNA Cleavage.

Calicheamicin γ1 and related natural products are renowned for their potency in DNA cleavage, serving as the warheads in commercial ADCs used for treating leukemia. Their mechanism of action involves the formation of aryl radicals, which abstract hydrogen atoms from nucleic acids. However, the complex strained enediyne structure of calicheamicin γ1 presents significant challenges in synthesis, resulting in high production costs and limited structural and activity modularity for tuning the therapeutic window. This report describes the development of simple molecular mimics based on diazonium salts, synthesized in fewer than 3 steps, capable of generating aryl radicals upon green or red light irradiation. SAR studies conducted on over 30 analogues reveal a wide range of potencies in DNA cleavage, with EC50 values ranging from low nanomolar to micromolar. Forming benzenoid diradicals does not appear to be necessary for potent DNA cleavage; instead, DNA cleavage can be achieved with radicals distributed among different arenes when connected with proper linkages. The potency is influenced by electronic effects, stereochemistry, orbital orientations, the distance between multiradicals, and the number of diazonium motifs within the molecule. In addition to providing a more cost-effective, efficient, and modular alternative to calicheamicin γ1, this technology offers the potential for enhanced specificity through spatiotemporal control.

Tailoring the Oxidizing Intermediate in the Fenton Reaction, OH⋅ or FeIV=Oaq, by Modifying the pKa of the (H2O)5FeII(H2O2) Complex, and the Case of PDS - a DFT Study.

A DFT analysis of the Fenton and Fenton-like reactions points out that the pH effect on the nature of the oxidizing intermediate formed is due to a pKa of the peroxide when hydroperoxides are used. When S2O8 2- is used, the pH effect is due to the pKa of one of the water ligands of the central iron cation. The results suggest that the choice of the hydroperoxide and the ligands present affects the pH at which the transition from the formation of hydroxyl radicals to the formation of FeIV=Oaq occurs.

„A szabadság fantomjai”

The rise to power of General Francisco Franco in Spain was followed after an extremely subversive civil war and bloody reprisals, which led most to perceive his system as oppressive and dictatorial. Correspondingly, various forms of anti-Francoist resistance characterized the regime from the moment of its establishment until its final days. One of the most radical and heroic forms of resistance was guerilla warfare, which unfolded over the years. Among its represent atives were active, persistent, and self-sacrificing participants from the anarchist movement in Spain. They either operated in the underground movement or were forced into exile after the civil war. This study attempts to briefly summarize the most important features of the guerilla activities maintained by anarchists, including its chronological and geographical aspects, as well as its tactics and methods. It also examines certain key actors – individuals, groups, and organizations – along with their motivations and the results they achieved.

Photocatalytic degradation of the remazol red ultra RGB dye using SrFe12O19-Fe3O4 magnetic oxides dispersed in silica: Effect of reduction temperature

Dyes are the most frequently discarded industrial wastes in aquatic ecosystems, among which Remazol Red ultra RGB stands out. In this context, magnetic iron-based catalyst dispersed in silica were prepared by Pechini route as an alternative for the photodegradation of Remazol Red Ultra RGB. The XRD and Mössbauer spectroscopy results indicated the formation of a magnetic material that, after reduction treatment with H2, forms a magnetite phase combined with Sr hexaferrite dispersed in amorphous silica. The TPR-H2 profiles indicated the reduction of Fe3+ to Fe2+ within the considered temperature range, the amount of Fe2+ increased with rising temperature. The SEM images showed sponge-like morphology for the samples. The EDS spectra and mapping confirmed a high uniformity in the distribution of active iron species in the silica. The magnetic measurements showed a lower magnetic signal for the sample reduced at 600 °C, due to the lower magnetic moment of Fe2+ formed after the reduction. The diffuse reflectance spectra showed a main absorption region between 500 and 200 nm and the estimated band-gap values were of 1.4 and 1.9 eV for the reduced sample and the fresh oxide, respectively. The surface charge was obtained via zeta potential, demonstrating good stability under pH changes and reaching a negative potential in the pH range from 2 to 6. The photocatalytic tests showed that the samples with higher content of Fe2+ demonstrated a greater photocatalytic degradation of the Remazol Red Ultra RGB dye, reaching 100 % degradation in 1 h for the solid reduced at 600 °C. A plausible mechanism for the photodegradation of Remazol Red Ultra RGB was proposed, considering the different elementary steps involving the participation of iron sites and the formation of oxidant radicals.

Photocatalyzed Direct C(sp3)-H Alkenylation of Unactivated Alkanes via Tandem C-C Activation of Cyclopropenes.

A highly adaptable method has been developed for the alkenylation of a broad spectrum of inert alkanes, employing milder reaction conditions. Tetrabutylammonium decatungstate (TBADT) serves as a photocatalyst for hydrogen atom transfer (HAT), instigating the formation of transient alkyl radicals through C(sp3)-H functionalization. These radicals exhibit regioselective addition to cyclopropenes, followed by the subsequent activation of C-C bonds, forming the corresponding vinylated derivatives. This methodology accommodates diverse unreactive C(sp3)-H bond motifs and multisubstituted cyclopropenes, enabling the efficient synthesis of highly functionalized olefins with high diastereoselectivity.