Stable Radical Research Articles

Investigating Solvent Effects on the Stability of the Diethylnitroxyl Radical via Electron Paramagnetic Resonance.

Operando electron paramagnetic resonance is used to monitor the light-initiated generation of the diethylnitroxyl radical from diethylhydroxylamine (DEHA) and its decay kinetics, thereby unveiling solvent effects on both the electronic structure and stability of the nitroxyl radical. The observed trends in hyperfine coupling constants (AN and AH) across different solvents align with previously reported values of the 4-amino-2,2,6,6-tetramethylpiperidoxyl radical (ATEMPO). Regarding the stability of the DEHA radical in various solvents, the obtained decay-kinetic constants (k) correlated more strongly with AN than with the permittivity of the solvents. Moreover, distinguishing between protic and aprotic solvents leads to a better relationship between AN and k, and a positive and constant correction of the nitroxyl radical's AN supports the hydrogen-bonding effect in protic solvents. These findings indicate that mere hydrogen-bonding interaction does not enhance the stability of radicals. AN of ATEMPO may serve as a superior metric for assessing the impact of solvent effects on both the electronic structure and stability of nitroxyl radicals. The data presented in this study will offer substantiation for the judicious selection of suitable solvents in reactions involving radicals.

Functionalized Terthiophene as an Ambipolar Redox System: Structure, Spectroscopy, and Switchable Proton-Coupled Electron Transfer.

Organic redox systems that can undergo oxidative and reductive (ambipolar) electron transfer are elusive yet attractive for applications across synthetic chemistry and energy science. Specifically, the use of ambipolar redox systems in proton-coupled electron transfer (PCET) reactions is largely unexplored but could enable "switchable" reactivity wherein the uptake and release of hydrogen atoms are controlled using a redox stimulus. Here, we describe the synthesis and characterization of an ambipolar functionalized terthiophene (TTH) bearing methyl thioether and phosphine oxide groups that exhibits switchable PCET reactivity. Electrochemical studies established that the functionalized TTH can be reversibly oxidized and reduced, prompting the synthesis and characterization of cationic and anionic radicals on a single TTH platform. Combined structural, spectroscopic, and computational investigations revealed the influence of the methyl thioether and phosphine oxide moieties on the TTH electronic structure that results in the stabilization of both cationic and anionic radicals. Upon single-electron oxidation, the functionalized TTH serves as a hydrogen atom acceptor and undergoes PCET with 1,4-dihydroquinone to generate a TTH hydroxyphosphonium species. The process was found to be reversible upon single-electron reduction, with functionalized TTH acting as a hydrogen atom donor in a PCET reaction with 2,3-dimethylanthraquinone. The thermochemistry of the O-H bond formed and cleaved in functionalized TTH during the reaction sequence was investigated, revealing that a bond weakening of 30 kcal/mol underpins the switchable PCET reactivity. Overall, these studies provide an electrochemical, structural, spectroscopic, and thermochemical foundation for the use of ambipolarity to control PCET reactions in organic redox systems.

Applications of Verdazyl Radicals in Energy Storage, Molecular Electronics and Magnetism: Teaching Old Molecules New Tricks.

Verdazyls are a fundamental class of stable organic radicals that have been traditionally overshadowed by the more synthetically accessible stable nitroxide radicals. With the advent of enhanced synthetic routes to verdazyls, particularly in recent years, these systems are now poised to realise their potential in a range of applications across emerging technologies that will be important to addressing challenges faced by modern society. This Concept discusses the enabling properties of a selection of verdazyl-based systems that feature promising applications in energy storage, molecular electronics and magnetic molecules. Emphasis is placed on progress in these areas over the past ~5 years.

High-k organic-inorganic hybrid dielectric material for flexible thin-film transistors and printed logic circuits.

A new photopolymerizable organic-inorganic (O-I) hybrid sol-gel material, AUP@SiOx-184, has been synthesized and utilized as a gate dielectric in flexible organic thin-film transistors (OTFTs). The previously reported three-arm alkoxy-functionalized silane amphiphilic polymer has yielded stable O-I hybrid materials comprising uniformly dispersed nanoparticles in the sol state. In this study, a photosensitizer was introduced, facilitating curing effects under ultraviolet light. Photo-crosslinking enhances the stability of hydroxyl radicals within inorganic nanoparticles, thereby minimizing device hysteresis. This approach also contributes to achieving a low leakage current and a high dielectric constant (high-k) while maintaining reduced thickness. Moreover, AUP@SiOx-184 films are amenable to patterning through UV photopolymerization and can be successfully produced using printing techniques. Compared to other materials, they exhibit outstanding flexibility and improved insulating capabilities. Additionally, OTFTs incorporating AUP@SiOx-184 layers demonstrate extremely stable driving features on flexible substrates. Selective printing and specific patterning play crucial roles in the fabrication of logic circuits. This synthesis strategy has resulted in integrated logic devices that have successfully demonstrated their functionality, highlighting its value for producing functional O-I hybrid materials. Utilizing AUP@SiOx-184 as a gate dielectric in OTFTs showcases its potential to advance electronic technologies that are both flexible and high-performing.

Strain Release in Hydrogen Atom Transfer from 1,4-Disubstituted Cyclohexanes to the Cumyloxy Radical

A kinetic, product and computational study on the reactions of the cumyloxyl radical (CumO•) with 1,4-dimethyl- and 1,4-diphenylcyclohexanes is reported. The rate constants for hydrogen atom transfer (HAT) from the C-H bonds of these substrates to CumO•, together with the corresponding oxygenation product distributions reveal the role of strain release on reaction site-selectivity. Transition structures and activation barriers obtained by DFT calculations are in excellent agreement with the experimental results. Tertiary/secondary ratios of oxygenation products of 0.6, 1.0 and 3.3 were observed, for trans-1,4-dimethyl-, cis-1,4-dimethyl- and trans-1,4-diphenylcyclohexane, respectively. With cis-1,4-diphenylcyclohexane, exclusive formation of the diastereomeric tertiary alcohol products was observed. Within the two diastereomeric couples, the tertiary equatorial C-H bond in the cis- isomer is ∼6 and 27 times more reactive, respectively, than the tertiary axial ones, a behavior that reflects the release of 1,3-diaxial strain in the HAT transition state. The tertiary axial C-H bonds of the four substrates show remarkably similar reactivities in spite of the much greater stabilization of the benzyl radicals resulting from HAT from the 1,4-diphenylcyclohexanes. The lack of benzylic acceleration is discussed in the framework of Bernasconi’s “principle of non-perfect synchronization”.

Novel azo-based benzimidazole Schiff base ligand and its Co(II), Ni(II) Cu(II) complexes: computational and biological studies

A novel azo-based benzimidazole Schiff base ligand (FDSBI) was synthesized by the condensation reaction of 2-aminobenzimidazole with 4-fluorodiazenyl-salicylaldehyde. The ligand and its metal complexes were studied by elemental analysis, spectral analysis, and magnetic susceptibility measurement. The absorption spectra of the complexes evidence octahedral geometry. The structural properties of the Schiff base and its metal complexes were also proved by the treatment of density functional theory (DFT) calculation. Thermogravimetric analysis proved the coordinated and lattice water molecules. Cyclic voltammetry technique has been used to study the redox behavior of the copper (II) complex. The in vitro antibacterial and antifungal activities of the Schiff base and its coordinated compounds were screened against bacterial species (Staphylococcus aureus, Salmonella typhi, Escherichia coli, Bacillus subtilis) and Fungi (Candida albicans, Aspergillus niger) using well diffusion method. The obtained results have suggested that the metal complexes showed significant biological activity than ligand. The in vitro antioxidant activity of both the ligand and its metal (II) complexes was assessed through the utilization of the DPPH stable free radical. The result shows that the ligand possesses better antioxidant properties than metal (II) complexes. The second harmonic generation efficiency was analyzed for the ligand, demonstrating its potential application in nonlinear optical material.

Physical properties of chlorophyll–quinone conjugates prepared via Friedel–Crafts reaction

Pheophytin-a derivatives possessing plastoquinone and phylloquinone analogs in the peripheral 3-substituent were prepared by Friedel–Crafts reactions of a 3-hydroxymethyl-chlorin as one of the chlorophyll-a derivatives with benzo- and naphthohydroquinones, respectively, and successive oxidation of the 1,4-dihydroxy-aryl groups in the resulting dehydration products. The 3-quinonylmethyl-chlorins exhibited ultraviolet–visible absorption and circular dichroism spectra in acetonitrile, which were composed of those of the starting 3-hydroxymethyl-chlorin and the corresponding methylated benzo- and naphthoquinones. No intramolecular interaction between the chlorin and quinone π-systems was observed in the solution owing to the methylene spacer. The first reduction potentials of the quinone moieties in the synthetic conjugates were determined by cyclic voltammetry and shifted positively from those of the reference quinones. The former quinonyl groups were reduced more readily by approximately 0.1 V than the latter quinones, which was ascribable to the stabilization of the quinonyl anion radical by the nearby macrocyclic chlorin π-chromophore. This observation implied that the reduction potentials of quinones were regulated by the close pheophytin-a derivative by through-space interaction. Considering the charge shift from pheophytin-a anion radical to plastoquinone and phylloquinone in reaction centers of photosystems II and I, respectively, the reduction potentials of these quinones as a determinant factor of the rapid electron transfer process would be dependent on the pheophytin-a in the photosynthetic reaction centers of oxygenic phototrophs as well as on the neighboring peptides.

The effects of age and other individual factors on radiation induced ESR signals from fingernails.

Biodosimetry is crucial for assessing ionizing radiation exposure to guide medical responses. Electron spin resonance (ESR) spectroscopy using fingernails can be effectively used for both occupational and public dose assessments in radiological accidents because of their accessibility and ability to retain stable radiation-induced free radicals. However, despite two decades of research, challenges remain in achieving accurate fingernail dosimetry, mainly owing to the variation in ESR signals among individuals. The purpose of this study was to explore inter-individual differences in ESR signals in fingernails to improve the accuracy and reliability of extremity dosimetry. Fingernail samples were collected from 15 participants (age: 11-64 years), irradiated with X-rays (160 kV, 6.3 mA) at 0, 5, 10, and 20 Gy, and measured using ESR spectroscopy. The effects of individual factors, such as age, sex, health condition, and lifestyle, on radiation-induced ESR signals (RIS) were investigated. Younger participants exhibited stronger RIS intensities and a more linear dose-response relationship. The RIS intensity in female samples tended to be higher than that in male samples. Interestingly, the fingernals of middle-aged donors who regularly took vitamin supplements showed significantly higher ESR signal intensities than those of similar-age donors who did not take supplements. Notable reductions in RIS intensity during storage in a freezer were observed only in older donor samples irradiated at higher doses. These findings underscores the importance of considering age and other individual factors in the calibration for fingernail dosimetry.

Preparation, Modification, Quantitation, and Dentin Biomodification Activity of Selectively Enriched Proanthocyanidins.

To date, quantitative analysis of proanthocyanidin (PAC) containing materials including plant extracts and fractions depends on colorimetric assays or phloroglucinolysis/thiolysis combined with UV-HPLC analysis. Such assays are of limited accuracy, particularly lack specificity, require extensive sample preparation and degradation, and need appropriate physical reference standards. To address this analytical challenge and toward our broader goal of developing new plant-sourced biomaterials that chemically and mechanically modulate the properties of dental tissue for clinical interventions, we have characterized 12 different PAC DESIGNER (Depletion and Enrichment of Select Ingredients Generating Normalized Extract Resources) materials. The DESIGNER approach is carried out by using either centrifugal partition chromatography (CPC) or size-exclusion chromatography (SEC) for the selective enrichment of trimeric and tetrameric PACs. Moreover, the rare but biologically interesting A-type PAC DESIGNERs can now be generated successfully from their natural AB-type PAC precursors via phenol-oxidative intramolecular coupling initiated by a mixture of the stable radicals, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). Furthermore, to ensure the quality and stability of PAC DESIGNER materials, we developed a quantitative analysis of the total PAC content of the DESIGNER materials in the form of a quantitative NMR (qNMR) method using a non-PAC internal calibrant combined with diol-HPLC. The total PAC content was, thus, determined to be in a range of 67.5-96.9% by qNMR. We highlight the complementarity of diol-HPLC and qNMR to accurately assess the amount of PACs across a range of concentrations and PAC stability in the DESIGNER materials. This quantitative methodology paves the way to generate standardized DESIGNER and other PAC-containing materials and to perform rigorous quality control for dental (pre)clinical studies of PACs.

Covalent Organic Frameworks with Carbon‐centered Radical Sites for Promoting the 4e‐ Oxygen Reduction Reaction

Radical covalent organic frameworks (RCOFs) have demonstrated significant potential in redox catalysis and energy conversion applications. However, the synthesis of stable RCOFs with well‐defined neutral carbon radical centers is challenging due to the inherent radical instability, limited synthetic methods and characterization difficulties. Building upon the understanding of stable carbon radicals and structural modulations for preparing crystalline COFs, herein we report the synthesis of a crystalline carbon‐centered RCOF through a facile post‐oxidation process. Moreover, the RCOF demonstrated outstanding catalytic activity in the 4e‐ oxygen reduction reaction (ORR) with a half‐wave potential of 0.82 V (vs. RHE) and electron transfer number of 3.98, among the highest in reported COF‐based electrocatalysts. The promoted 4e‐ and suppressed 2e‐ ORR pathway (99.5% vs. 0.5%) can be attributed to facilitated reaction initiation and smoother transition steps at the carbon radical sites, which is practically beneficial for minimizing peroxide formation, thus contributing to safer and more sustainable fuel cell and metal‐air battery applications. Overall, our study not only provided a facile strategy for preparing stable RCOFs with well‐defined neutral carbon radical centers but also demonstrated their capability to fine‐tune the redox catalytic activity of COF materials, which could be potentially useful in electrocatalysis and energy conversion applications.

Covalent Organic Frameworks with Carbon-Centered Radical Sites for Promoting the 4e- Oxygen Reduction Reaction.

Radical covalent organic frameworks (RCOFs) have demonstrated significant potential in redox catalysis and energy conversion applications. However, the synthesis of stable RCOFs with well-defined neutral carbon radical centers is challenging due to the inherent radical instability, limited synthetic methods and characterization difficulties. Building upon the understanding of stable carbon radicals and structural modulations for preparing crystalline COFs, herein we report the synthesis of a crystalline carbon-centered RCOF through a facile post-oxidation process. Moreover, the RCOF demonstrated outstanding catalytic activity in the 4e- oxygen reduction reaction (ORR) with a half-wave potential of 0.82 V (vs. RHE) and electron transfer number of 3.98, among the highest in reported COF-based electrocatalysts. The promoted 4e- and suppressed 2e- ORR pathway (99.5 % vs. 0.5 %) can be attributed to facilitated reaction initiation and smoother transition steps at the carbon radical sites, which is practically beneficial for minimizing peroxide formation, thus contributing to safer and more sustainable fuel cell and metal-air battery applications. Overall, our study not only provided a facile strategy for preparing stable RCOFs with well-defined neutral carbon radical centers but also demonstrated their capability to fine-tune the redox catalytic activity of COF materials, which could be potentially useful in electrocatalysis and energy conversion applications.

Hydroxyl Radical-π Interaction in a Single Crystal.

Numerous attempts for organic radical stability mostly entail steric hindrance, spin-delocalization, supramolecular interaction with the host, π-π interactions, and hydrogen bonding. To date, there is no report of single crystals containing a hydroxyl radical (•OH). In this work, we have stabilized •OH in the crystal, which has been obtained from the filtrate after separating the precipitate of the chromenopyridine radical (DCP(2)•) from the reaction mixture. DCP(2)• abstracts a hydrogen atom from dissolved water in the ethanolic filtrate to grow the single crystal containing DCPH(2) and •OH in the asymmetric unit. The crystal packing and computational studies suggest that π-•OH and •OH···N hydrogen-bonding interactions are responsible for stabilizing •OH. The presence of •OH has been further confirmed by mass analysis with the 2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) adduct. Solid-state electron paramagnetic resonance (EPR), solution state nitroblue tetrazolium (NBT) assay, and spin trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in the presence of super oxide dismutase suggest •OH formation in the single crystal.

Through Space π‐Electrons Communication in [2,2]‐Paracyclophanes: Unprecendented Stabilization of Radicals

AbstractEfforts to understand radical stability have led to considerable progress in radical chemistry. In this article, we investigated a novel approach to enhancing the radical stability of carbon‐centered radicals through space electron delocalization within [2,2]‐paracyclophanes. Alkoxyamines possessing a paracyclophane scaffold exploit face‐to‐face π‐π‐interactions between the aromatic rings to effectively lower bond dissociation energy (BDE) for NO−C bond homolysis. Electron spin resonance (ESR) experiments and computational modeling have confirmed a better stability compared to the analogues without the paracyclophane core. Theoretical analyses further elucidate the role of through‐space electron communication in enhancing radical stability. This study highlights promising applications in fields such as organic synthesis, material science, and drug design. By achieving a low BDE for homolysis, the alkoxyamines efficiently release radicals, enabling successful application in nitroxide‐mediated polymerization (NMP) of styrene, which provides high control over polymer architecture. Additionally, preliminary anti‐proliferative assays reveal that the alkoxyamines exhibit promising anti‐cancer activities against lung, breast, and prostate cells, which is correlated to their ability to release radicals upon homolysis.

Isolated Neutral Organic Radical Unveiled Solvent-Radical Interaction in Highly Reducing Photocatalysis.

Diffusion-limited kinetics is a key mechanistic debate when consecutive photoelectron transfer (conPET) is discussed in photoredox catalysis. In situ generated organic photoactive radicals can access catalytic systems as reducing as alkaline metals that can activate remarkably stable bonds. However, in many cases, the extremely short-lived transient nature of these doublet state open-shell species has led to debatable mechanistic studies, hindering adoption and development. Herein, we document the use of an isolated and stable neutral organic nPrDMQA radical as a highly photoreducing species. The isolated radical offers a unique platform to investigate the mechanism behind the photocatalytic activity of organic photocatalyst radicals. The involvement of reduced solvent is observed, formed by single electron transfer (SET) between the short-lived excited state nPrDMQA radical and the solvent. In our detailed mechanistic studies, spectroscopic and chemical affirmation of solvent reduction is strongly evident. Reduction of aryl halides, including difluoroarenes is presented as a model study of the conPET method. Further, the activation of N2O, a greenhouse gas that is yet to be activated by photoredox catalysis, is showcased in the absence of a transition metal.

Non-Kekulé copolymer films for optoelectronics

Copolymers of graphitic carbon nitride and graphitic carbon (gCN-co-gC) are synthesized using melamine and glucose. They act as semiconductors with stable radicals, even in the dark and at room temperature.

Improved voltage and solubility in hybrid non-aqueous redox flow batteries using a molecular 3,4-ethylenedioxythiophene (EDOT) derivative with a stable radical cation state

A molecular ethylenedioxythiophene (EDOT) derivative is explored in hybrid lithium redox flow batteries. t-Butyl groups prevent polymerization & protolysis, resulting in a reversibly oxidizable molecule with excellent positive-charge-storing ability.

Viridium: A Stable Radical and Its π-Dimerization.

The discovery of a stable organic radical formed under mild, clean, and efficient light-mediated conditions is reported. The structure of the stable acridinium-based radical photoproduct was unambiguously established by single-crystal X-ray diffraction, mass spectrometry, and in solution by EPR, UV/vis, and NMR spectroscopies. The photochemical mechanism of its formation has been elucidated by photophysical experiments coupled with EPR experiments and theoretical investigations. This unique aromatic radical is featured by amphoteric redox behavior and π-dimerization properties. Its ability to π-dimerize has been demonstrated in water and in the less studied perfluorohexane, two solvents of opposite polarity. By a simple counterion exchange, direct comparison of π-dimer thermodynamics between both antagonist solvents allowed an elucidation of the solvophobic behavior in perfluorocarbon.

Synthesis and Characterization of Functionalized Poly(9-vinylcarbazole) for light-emitting diode applications

Organic light-emitting diode (OLED) has been successfully applied to replace conventional lighting systems due to its ability to adjust color emission, low energy consumption, and high contrast ratio. One of the polymers of interest in this area is polyvinyl carbazole, PVK, given its characteristics, such as forming stable radicals, high thermal and photochemical stability, and high charge carrier mobility. The modification of PVK has contributed positively to its performance as an electroluminescent layer in the constitution of OLED devices, as seen in works carried out by Mota & Marques (2019); Brito & Marques (2020); Correia & Marques (2022); Geffroy & Grana (2019); Pachariyangkun & Suda (2020). The present study aimed to synthesize and functionalize poly(9-vinylcarbazole) as well as its characterization by thermoanalytical (TG, DTA and DSC) and spectroscopic (FTIR) techniques in order to verify the efficiency of the proposed synthesis. To date, no studies have been found in the literature using the compound 3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-dibenzofuran in PVK for application in the emitting layer of optoelectronic devices.

A Trithia‐Bridged N‐Heterotriangulene: The Hitherto Missing Electron Donor

AbstractThe very first representative of trithia‐bridged N‐heterotriangulene, a triphenylamine with sulfur atoms bridging the ortho‐positions, was synthesized by a sequence of regioselective sulfenylation with phthalimidesulfenyl chloride followed by Lewis acid‐catalyzed electrophilic cyclization. X‐ray crystallography revealed a saddle‐shaped geometry of the polycyclic scaffold. UV/Vis absorption spectroscopy and cyclic voltammetry were used to characterize the optoelectronic properties. The title compound is a particularly strong electron donor forming a perfectly stable radical cation, which was analyzed by electron paramagnetic resonance spectroscopy and X‐ray crystallography. The electron donor properties were further highlighted by the formation of crystalline donor‐acceptor complexes with strong cyano‐based acceptors.

Through Space π-Electrons Communication in [2,2]-Paracyclophanes: Unprecendented Stabilization of Radicals.

Efforts to understand radical stability have led to considerable progress in radical chemistry. In this article, we investigated a novel approach to enhancing the radical stability of carbon-centered radicals through space electron delocalization within [2,2]-paracyclophanes. Alkoxyamines possessing a paracyclophane scaffold exploit face-to-face π-π-interactions between the aromatic rings to effectively lower bond dissociation energy (BDE) for NO-C bond homolysis. Electron spin resonance (ESR) experiments and computational modeling have confirmed a better stability compared to the analogues without the paracyclophane core. Theoretical analyses further elucidate the role of through-space electron communication in enhancing radical stability. This study highlights promising applications in fields such as organic synthesis, material science, and drug design. By achieving a low BDE for homolysis, the alkoxyamines efficiently release radicals, enabling successful application in nitroxide-mediated polymerization (NMP) of styrene, which provides high control over polymer architecture. Additionally, preliminary anti-proliferative assays reveal that the alkoxyamines exhibit promising anti-cancer activities against lung, breast, and prostate cells, which is correlated to their ability to release radicals upon homolysis.