Stable Radical Research Articles

Using a Stable Radical as an “Electron Donor” to Develop a Radical Photosensitizer for Efficient Type-I Photodynamic Therapy

Among type I photosensitizers, stable organic radicals are superior candidate molecules for hypoxia-overcoming photodynamic therapy. While their wide applications are limited by complicated preparation processes and poor stabilities. Herein, a...

Construction of a stable radical hydrogen-bonded metal-organic framework with functionalized tetrathiafulvalene linkers.

A stable two-dimensional radical hydrogen-bonded metal-organic framework, constructed using a modified tetrathiafulvalene-tetrabenzoate ((2-Me)-H4TTFTB) linker and Cd2+ ions, exhibits a high electrical conductivity of 4.1 × 10-4 S m-1 and excellent photothermal conversion with a temperature increase of 137 °C in 15 s under the irradiation of a 0.7 W cm-2 808 nm laser.

Thermal-induced coloration and photothermal conversion of an Ag-based coordination polymer with stable radicals

An exceptional crystalline material only composed of non-radical components, exhibits radical-doping nature both under ambient conditions and high temperature of 400 °C. Temperature can induce its color, spectra and photothermal property variations.

A stable radical within a N-Co-N core.

A N-Co-N core is embedded within [Co(CNC)2]2+ (1) supported by two bis(4-methyl-2-(3-methyl-imidazolium)phenyl)amine (CNC) ligands. This species reveals a stable S = 1/2 state and its spin density is significantly delocalized within the N-Co-N core via parallel π-bonding interaction. Interestingly, it displays unusual stability towards O2 and water, proving that the core is well protected. Upon reduction, compound 1 was converted to its reduced diamagnetic species [Co(CNC)2]+ (2) having two amide donors and a low-spin Co(III) ion, which can be oxidized by air to regenerate 1.

Electrochemical ring-opening carboxylation of cyclic carbonate with carbon dioxide.

Electroreductive ring-opening carboxylation of styrene carbonates with CO2 to achieve dicarboxylic acids and/or β-hydroxy acids has been developed via the selective cleavage of the C(sp3)-O bond in cyclic carbonates. The product selectivity is probably determined by the stability and reactivity of the key benzylic radical and carbanion intermediate.

Effects of alcohols as sacrificial reagents on a copper-doped sodium dititanate nanosheets/graphene oxide photocatalyst in CO2 photoreduction.

Carbon dioxide (CO2) photoreduction is an intriguing approach that converts CO2 into high-value substances with the assistance of a photocatalyst. Key to effective photoreduction is to promote the interaction of photo-induced holes and a sacrificial reagent (SCR), separating the holes from photoelectrons and enhancing the rate of the subsequent product generation. Methanol, ethanol, isopropanol, and water SCRs were tested for their ability to assist a copper-doped sodium dititanate nanosheets/graphene oxide heterostructure (CTGN) in CO2 photoreduction. The CTGN photocatalyst was suspended in a CO2-saturated aqueous solution with the assigned SCR while illuminated by a mercury lamp. Product samples from the gas and liquid phases were analyzed for targeted product compositions. Methanol SCR exhibited the best performance in facilitating CO2 photoreduction, producing ethanol as the main product at a total carbon consumption (TCC) of 6544 μmol gcat -1. The remarkable performance of methanol is attributed to the high diffusivity and excellent stability of the hydroxymethyl radical that developed during the photoreduction. The kinetics studies revealed the first and second order for the CO2 depletion and product generation rates, respectively, for the alcohol SCRs.

α-Amino bicycloalkylation through organophotoredox catalysis.

Bridged bicycloalkanes such as bicyclo[1.1.1]pentanes (BCPs) and bicyclo[3.1.1]heptanes (BCHeps) are important motifs in contemporary drug design due to their potential to act as bioisosteres of disubstituted benzene rings, often resulting in compounds with improved physicochemical and pharmacokinetic properties. Access to such motifs with proximal nitrogen atoms (i.e. α-amino/amido bicycloalkanes) is highly desirable for drug discovery applications, but their synthesis is challenging. Here we report an approach to α-amino BCPs and BCHeps through the visible-light enabled addition of α-amino radicals to the interbridgehead C-C bonds of [1.1.1] and [3.1.1]propellane respectively. The reaction proceeds under exceptionally mild conditions and displays broad substrate scope, providing access to an array of medicinally-relevant BCP and BCHep products. Experimental and computational mechanistic studies provide evidence for a radical chain pathway which depends critically on the stability of the α-amino radical, as well as effective catalyst turnover.

APPLICATION OF SULFUR RADICAL ANIONS IN ORGANIC SYNTHESIS. DETERMINATION OF FORMS OF SULFUR

The study of reactions involving sulfur anion radicals in organic synthesis has become an area of active research in the last few years. The role of polysulfide radicals in the electrochemical processes of lithium-sulfur (Li-S) batteries has been particularly discussed. Understanding the pathways of the electrochemical reactions is crucial for improving the performance of Li-S batteries. In order to summarize and analyze the most relevant literature data, the review presents information on the application and study of sulfur anion radicals in organic synthesis and methods for the determination of sulfur forms. We have classified and discussed in detail the spectra of various forms of sulfur in the ultraviolet and visible ranges. The article describes the choice of solvent, the correlation between the properties of solvents, the influence of the nature of the solvent on the absorption band shift of sulfur particles and on the stability of the anion radical, the identification of sulfur forms in the ultraviolet and visible spectrum regions, and the possibility of stabilizing anion radicals by complexation with crown ethers. The absorption bands for S22-, S32-, S52-, S72- strongly overlap with other particles while having lower intensities, leading to different conclusions regarding the distribution of polysulfides and different forms of sulfur in aqueous media. The data presented in the review have an applied meaning, contribute to the understanding of the application of sulfur anion radicals in organic synthesis and can be used for the choice of method for the determination of sulfur forms and solvent. This review article may be of interest to specialists in the field and will help to plan studies on the study of sulfur forms and the interpretation of spectra of different sulfur forms.

A high-spin s-triazine linked fluorenyl radical polymer.

The syntheses of high-spin organic polymers have been a daunting task due to the highly reactive nature of organic radicals, especially when they are ferromagnetically coupled. In this paper, we report our approach to obtain high-spin organic polymers, in which a reasonably stable fluorenyl radical was employed as the primary radical unit, and s-triazine serves as the connector that facilitates ferromagnetic coupling between them. Initially, the diamagnetic polymer precursor was synthesized by cyclotrimerization of a cyano-monomer. Subsequently, the high-spin polymers were obtained by oxidizing corresponding anionic polymers using O2 (6) or I2 (7). The temperature-dependent magnetic moments, and field-dependent magnetization data obtained from SQUID measurements revealed ferromagnetic couplings between primary radical units, with coupling J = 7.5 cm-1 and 38.6 cm-1. The percentages of primary unit in the radical form are 29%, and 47% for 6 and 7, respectively. Notably, this marks the first reported instance of a high-spin fluorenyl radical polymer exhibiting ferromagnetic coupling.

Radical enhanced intersystem crossing mechanism, electron spin dynamics of high spin states and their applications in the design of heavy atom-free triplet photosensitizers.

Heavy atom-free triplet photosensitizers (PSs) can overcome the high cost and biological toxicity of traditional molecular systems containing heavy atoms (such as Pt(II), Ir(III), Ru(II), Pd(II), Lu(III), I, or Br atoms) and, therefore, are developing rapidly. Connecting a stable free radical to the chromophore can promote the intersystem crossing (ISC) process through electron spin exchange interaction to produce the triplet state of the chromophore or the doublet (D) and quartet (Q) states when taking the whole spin system into account. These molecular systems based on the radical enhanced ISC (REISC) mechanism are important in the field of heavy atom-free triplet PSs. The REISC system has a simple molecular structure and good biocompatibility, and it is especially helpful for building high-spin quantum states (D and Q states) that have the potential to be developed as qubits in quantum information science. This review introduces the molecular structure design for the purpose of high-spin states. Time-resolved electron paramagnetic resonance (TREPR) is the most important characterization method to reveal the properties of these molecular systems, generation mechanism and electron spin polarization (ESP) of the high spin states. The spin polarization manipulation of high spin states and potential application in the field of quantum information engineering are also summarized. Moreover, molecular design principles of the REISC system to obtain long absorption wavelength, high triplet state quantum yield and long triplet state lifetime are introduced, as well as applications of the compounds in triplet-triplet annihilation upconversion, photodynamic therapy and bioimaging. This review is useful for the design of heavy atom-free triplet PSs based on the radical-chromophore molecular structure motif and the study of the photophysics of the compounds, as well as the electron spin dynamics of the multi electron system upon photoexcitation.

Comparative evaluation of the antianxiety effects of Vitamin C, buspirone, and diazepam in rats

Background: Anxiety is one of the common mental disorders. Non-fatal health loss is one of the consequences of anxiety disorders. Oxidative stress may also play a role in anxiety disorders. As an antioxidant, Vitamin C can create stable ascorbate free radicals and lower reactive oxygen species. In addition, Vitamin C can prevent damage caused by free radicals. Oxidative stress can also lead to depression, schizophrenia, and bipolar disorder. Aim and Objectives: The aim and objectives of the study are to compare the antianxiety effects of Vitamin C, buspirone, and diazepam in albino rats using elevated plus maze and hole board apparatus. Materials and Methods: 36 albino rats of either sex were divided into 6 groups of 6 rats each and drugs were administered orally. Group 1 received distilled water 10 ml/kg, Group 2 received Vitamin C 200 mg/kg, Group 3 received buspirone 10 mg/kg, Group 4 received diazepam 1 mg/kg, Group 5 received buspirone 10 mg/kg + Vitamin C 200 mg/kg, and Group 6 received diazepam 1 mg/kg + Vitamin C 200 mg/kg. Antianxiety effects of these drugs were tested after 14 days of drug administration using hole board apparatus and elevated plus maze. The methods used for statistical analysis were mean, standard deviation, confidence interval, median, interquartile range (IQR), frequency and percentage, ANOVA, Kruskal–Wallis test, and Fisher’s exact test. Results: On average time spent in open arms by Group 5 was 98.00 sec (IQR: 19.75–138.00) which was higher than other groups, but it was not statistically significant (P = 0.845). The time spent in closed arms in seconds by Group 4 was 245 ± 28.863, which was higher than other groups, but it was not statistically significant (P = 0. 805). On average head dip by Group 5 was 9.83 ± 4.708, which was higher than other groups, but it was not statistically significant (P = 0.141). Conclusion: Group 5 rats that received buspirone and Vitamin C, followed by Group 6 rats that received diazepam and Vitamin C had spent more time and had more entries into the open arms. Furthermore, Groups 5 and 6 animals had a greater number of head dips in the hole board apparatus compared to the behavior of all animals in other groups. Buspirone and diazepam are known anxiolytics. When these drugs were given in combination with Vitamin C, the antianxiety behaviors in rats were more compared to the drugs given alone in the present study but it was not statistically significant.

Unusual reactivity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) with Fe3+ controlled by competing reactions.

2,2-Diphenyl-1-picrylhydrazyl (DPPH) is a stable organic free radical widely used in various fields as a model free radical. There is scarce information about the stability of this compound in the chemical environments in which it is used. Side reactions between DPPH and other species can alter the precision of experiments that use DPPH, such as the evaluation of antioxidant properties amongst others. Following recent investigations highlighting reactions between DPPH and metal cations or Lewis acids, a quantitative reaction between DPPH and Fe3+ in acetonitrile was studied in the present work. UV-Vis spectroscopy and electrochemistry were used to monitor the reaction. The results obtained indicate a fast and multistep reaction between Fe3+ and DPPH that can be simplified as a simple redox reaction with the formation of Fe2+ and DPPH+. The reaction mechanism proposed follows complex steps involving two competing phenomena: a disproportionation which accelerates the reaction and an oxidation process that slows it down through DPPH regeneration.

Cyano modified triphenylmethyl radical skeletons: higher stability and efficiency.

We introduced cyano groups to replace chlorine atoms in the tris(2,4,6-trichlorophenyl)methyl (TTM) radical skeleton, resulting in two cyano-modified TTM skeletons. The incorporation of cyano groups effectively suppresses nonradiative transition processes and lowers the frontier molecular orbital energy levels compared to those of the TTM radical. Consequently, enhanced photoluminescence quantum efficiency (PLQE) and a shift towards longer-wavelength emission in solution were achieved. Furthermore, the cyano-modified TTM skeletons exhibited improved stabilities. The development of these two skeletons adds diversity to stable organic luminescent radical skeletons.

Изучение состава фенольных соединений, антирадикальной активности и влияния на фагоцитоз сухого водного экстракта шишек сосны обыкновенной

Pine cone is a new promising type of plant raw material for using in a medical practice. Objective: determination of the phenolic compounds composition of pine cones dry aqueous extract, research of its toxicity, antiradical activity and effect on phagocytosis. Materials and methods. The research object was a collection of pine cones gathered in October 2020. A dry aqueous extract was obtained from the cones by extraction with hot water. The phenolic compounds composition of the pine cones dry aqueous extract was determined by ultra-efficient liquid chromatography/MS on a Waters Acquisition chromatograph with a diode-matrix UV detector and a tandem quadrupole MC detector TQD (Waters). To determine the antiradical activity, a reaction with a stable free radical, 2,2-diphenyl-1-picrylhydrazyl (DPPH), was used. The acute toxicity of the pine cones dry extract was researched by the V.V. Prozorovsky express method on white non-linear mice. The phagocytic activity of peripheral blood leukocytes was determined in vivo by a modified method. Results. The phenolic compounds composition of the extract was analysed. The research identified 12 substances present in the extract, representing at least 1% of the total area on the chromatogram. The following procyanidins were found in the pine cones extract: procyanidin B2, procyanidin B3, procyanidin C1, procyanidin D1. Additionally, flavonoids and phenolic carboxylic acids were identified. The pine cones dry extract demonstrated pronounced antiradical activity, comparable to that of ascorbic acid. The acute toxicity determination revealed that the LD50 of the researched compounds is in doses greater than 1260 mg/kg. Upon examination of the effect of pine cone extract on the phagocytic activity of peripheral blood leukocytes, an increase in the phagocytic index was observed, yet no change was noted in the activity of total leukocyte phagocytosis. Conclusion. The dry aqueous extract of pine cones contains biologically active components of phenolic nature, which suggests that further research into its pharmacological activity may be promising.

A water-soluble aza-adamantyl nitroxide radical and its complexes with β-cyclodextrin derivatives

A water-soluble, stable aza-adamantyl nitroxide radical has been synthesized. Complexation with selected β-cyclodextrin derivatives increases its water-solubility and maintains well the stability of the radical.

Chemical profile and biological potential of essential oil of Psidium bahianum Landrum & Funch (Myrtaceae).

The genus Psidium, belonging to the family Myrtaceae, encompasses several plant species rich in essential oils. Several studies involving different research areas have shown promising results for essential oils, which has attracted interest from diverse sectors, including pharmaceutical, food, and cosmetic industries. Thus, the objective of this study was to evaluate the biological activity of the essential oil extracted from Psidium bahianum leaves (EOPb) collected in an Atlantic Forest remnant in the northern coast of the state of Bahia, Brazil. EOPb was extracted by steam distillation and analyzed through proton nuclear magnetic resonance (1H-NMR). The free radical scavenging activity was assessed using the DPPH methodology (analyzing the scavenging of the stable free radical 1,1-diphenyl-2-picrylhydrazyl). Antimicrobial disk diffusion assays were conducted; toxicity was determined through assays on sheep erythrocytes and Artemia salina. 1H-NMR evaluation showed the presence mainly of monoterpenes and sesquisterpenes. The percentage of antioxidant activity was 18.03±2.53 53 for 125 125 µg mL-1. Antimicrobial assays showed that the essential oil at a concentration of 10 mg mL-1 inhibited the growth of the microorganisms Staphylococcus aureus, Bacillus subtilis, B. cereus, Micrococcus luteus, Escherichia coli, Aspergillus niger, Candida albicans, and C. glabrata. The toxicity results indicated that concentrations of EOPb at 10, 100, 250, and 500 µg mL-1 were not toxic to sheep erythrocytes. The toxicity assay on A. salina showed that the lethal concentration for 50% of individuals (LC50) within 24 and 48 hours were 371.48 and 302 µg mL-1 of EOPb, respectively, which were considered moderately toxic, whereas the LC50 within 72 horas was 33.11 µg mL-1, considered highly toxic. These findings are promising, as the essential oil from P. bahianum leaves showed antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungi. The data obtained for the essential oil toxicity in A. salina could be tested on different tumor cell lines.

One pot oxygen mediated syntheses of stable radicals

Aerial oxygen and base mediated synthesis is performed for three unprecedented neutral carbon centered radicals in solid state, whose emissions and stabilities depend on C(sp3)-, C(sp2)- or H-substitution at the radical center.

A radical containing micellar probe for assessing esterase enzymatic activity with ultra-low field Overhauser-enhanced magnetic resonance imaging.

The ability to track altered enzyme activity using a non-invasive imaging protocol is crucial for the early diagnosis of many diseases but is often challenging. Herein, we show that Overhauser magnetic resonance imaging (OMRI) can be used to monitor enzymatic conversion at an ultra-low field (206 μT) using a highly sensitive "off/on" probe with a nitroxide stable radical containing ester, named T2C12-T80. This TEMPO derivative containing probe forms stable electron paramagnetic resonance (EPR) silent micelles in water that are hydrolysed by esterases, thus yielding narrow EPR signals whose intensities correlate directly with specific enzymatic activity. The responsiveness of the probe to tumours, facilitated by increased esterase activity, was initially determined by comparing EPR signals measured upon incubation with 3T3 (healthy fibroblasts used as control), HepG2 (human hepatoma) and Hs766T (human pancreatic cancer cells) cell lysates and then with Hs766T and 3T3 living cells. Next, Overhauser MR images were detected on a phantom containing the probe and the esterases to show that the approach is well suited for being translated to the in vivo detection at the earth's magnetic field. Regarding detection sensitivity, ultra-low field OMRI (ULF-OMRI) is beneficial over OMRI at higher fields (e.g. 0.2 T) since Overhauser enhancements are significantly higher and the technique is safe in terms of the specific absorption rate.

Perylenemonoimide-based superstable radical anions and dianions with solid-state emission properties

The ambient stable radical anions originated from perylenemonoimide via sulfur oxidation was explored in this investigation.

Synthesis of NiII porphyrin-NiII 5,15-diazaporphyrin hybrid tapes.

NiII porphyrin (P) and NiII 5,15-diazaporphyrin (DAP) hybrid tapes were synthesized by Suzuki-Miyaura cross-coupling reactions of meso- or β-borylated P with β-brominated DAP followed by intramolecular oxidative fusion reactions. Meso-β doubly linked hybrid tapes were synthesized by oxidation of singly linked precursors with DDQ-FeCl3. Synthesis of triply linked hybrid tapes was achieved by oxidation with DDQ-FeCl3-AgOTf with suppression of peripheral β-chlorination. In these tapes, DAP segments were present as a 20π-electronic unit, but their local antiaromatic contribution was trivial. Remarkably, these hybrid tapes were stable and exhibited extremely enhanced absorption bands in the NIR region and multiple reversible redox waves. A pentameric hybrid tape showed a remarkably sharp and red-shifted band at 1168 nm with ε = 5.75 × 105 M-1 cm-1. Singly linked P-DAP dyads were oxidized with DDQ-FeCl3 to give stable radicals, which were oxidized further to afford dimeric hybrid tapes possessing a nitrogen atom at the peripheral-side meso-position.