Stable Radical Research Articles

Step-growth irreversible deactivation radical polymerization: synergistic developments with chain-growth reversible deactivation radical polymerization

Abstract Recent advances in chain-growth reversible deactivation radical polymerization (CG-RDRP), i.e. the so-called “living radical polymerization”, have synergistically developed step-growth radical polymerizations via controlled formation of radical species from covalent bonds followed by irreversible deactivation of the resulting radical species. The monomers for radical polyaddition are thus designed to possess carbon–halogen or thioester bonds, which can generate radical species in the presence of transition metal catalysts and radical initiators, as well as carbon‒carbon double bonds, which will irreversibly form carbon–halogen or thioester bonds. Radical polycondensations are achievable via radical coupling reactions of carbon-centered radicals generated from carbon–halogen bonds or radical quenching reactions with nitroxides. Furthermore, radical addition-condensation polymerizations are achieved by a sequence of reactions, i.e. the formation of radical species from carbon–halogen bonds, radical addition to nitroso or thiocarbonylthio compounds, and coupling or quenching reactions with the resulting stable radical. These step-growth irreversible deactivation radical polymerizations (SG-IDRP) enable the synthesis of a variety of polymers, such as polyethers, polyesters, polyamides, and polyimides, which have aliphatic, aromatic, polar, and degradable groups in their main chains. Sequence-regulated vinyl polymer structures can also be constructed by designing monomers. Combinations with CG-RDRPs further lead to unique hybrid block, multiblock, graft, hyperbranched, and network polymers.

Supramolecular Chiral Aggregation of Porphyrin Induced by Photo-Generated Triphenylamines Radical Cations.

Here, it is shown that photoirradiation triggered chiral J-aggregates formation of an achiral anionic porphyrin, TPPS (tetrakis(4-sulfonatophenyl) porphyrin), in the presence of chiral triphenylamine (TPA) derivatives. A series of chiral triarylamines linked with aromatic rings is designed through urea or amide bonds. UV-irradiation of self-assembled urea-linked triphenylamine derivatives causes the formation of persistent radical cations in the chlorinated solvents, which subsequently induces the aggregation of TPPS. Transferring chirality of TPA derivatives to achiral TPPS J-aggregates leads to the chiral assemblies with remarkable chiroptical signals. The experimental results demonstrate that, TPA derivatives linked by the urea bond can effectively promote the aggregation of TPPS rather than those with the amide bond although the photo-generated radical cations are both produced. It is suggested that the urea-linked TPA derivatives are more favorable to stable radical cations and thus cause the formation of TPPS chiral J-aggregation. This work may open up an avenue for designing photo-modulated chiral supramolecular assemblies.

Energetics of the OH radical H-abstraction reactions from simple aldehydes and their geminal diol forms.

Carbonyl compounds, especially aldehydes, emitted to the atmosphere, may suffer hydration in aerosols or water droplets in clouds. At the same time, they can react with hydroxyl radicals which may add or abstract hydrogen atoms from these species. The interplay between hydration and hydrogen abstraction is studied using density functional and quantum composite theoretical methods, both in the gas phase and in simulated bulk water. The H-abstraction from the aldehydic and geminal diol forms of formaldehyde, acetaldehyde, glycolaldehyde, glyoxal, methylglyoxal, and acrolein is studied to determine whether the substituent has any noticeable effect in the preference for the abstraction of one form or another. It is found that abstraction of the H-atom adjacent to the carbonyl group gives a more stable radical than same abstraction from the geminal diol in the case of formaldehyde, acetaldehyde, and glycolaldehyde. The presence of a delocalizing group in the Cα (a carbonyl group in glyoxal and methylglyoxal, and a vinyl group in acrolein), reverts this trend, and now the abstraction of the H-atom from the geminal diol gives more stable radicals. A further study was conducted abstracting hydrogen atoms from the other different positions in the species considered, both in the aldehydic and geminal diol forms. Only in the case of glycolaldehyde, the radical formed by H-abstraction from the -CH2OH group is more stable than any of the other radical species. Abstraction of the hydrogen atom in one of the hydroxyl groups in the geminal diol is equivalent to the addition of the •OH radical to the aldehyde. It leads, in some cases, to decomposition into a smaller radical and a neutral molecule. In these cases, some interesting theoretical differences are observed between the results in gas phase and (simulated) bulk solvent, as well as with respect to the method of calculation chosen. DFT (M06-2X, B2PLYP, PW6B95), CCSD(T), and composite (CBS-QB3, jun-ChS, SCVECV-f12) methods using Dunning basis sets and extrapolation to the CBS limit were used to study the energetics of closed shell aldehydes in their keto and geminal-diol forms, as well as the radical derived from them by hydrogen abstraction. Both gas phase and simulated bulk solvent calculations were performed, in the last case using the Polarizable Continuum Model.

Nucleotide binding to the ATP-cone in anaerobic ribonucleotide reductases allosterically regulates activity by modulating substrate binding.

A small, nucleotide-binding domain, the ATP-cone, is found at the N-terminus of most ribonucleotide reductase (RNR) catalytic subunits. By binding adenosine triphosphate (ATP) or deoxyadenosine triphosphate (dATP) it regulates the enzyme activity of all classes of RNR. Functional and structural work on aerobic RNRs has revealed a plethora of ways in which dATP inhibits activity by inducing oligomerisation and preventing a productive radical transfer from one subunit to the active site in the other. Anaerobic RNRs, on the other hand, store a stable glycyl radical next to the active site and the basis for their dATP-dependent inhibition is completely unknown. We present biochemical, biophysical, and structural information on the effects of ATP and dATP binding to the anaerobic RNR from Prevotella copri. The enzyme exists in a dimer-tetramer equilibrium biased towards dimers when two ATP molecules are bound to the ATP-cone and tetramers when two dATP molecules are bound. In the presence of ATP, P. copri NrdD is active and has a fully ordered glycyl radical domain (GRD) in one monomer of the dimer. Binding of dATP to the ATP-cone results in loss of activity and increased dynamics of the GRD, such that it cannot be detected in the cryo-EM structures. The glycyl radical is formed even in the dATP-bound form, but the substrate does not bind. The structures implicate a complex network of interactions in activity regulation that involve the GRD more than 30 Å away from the dATP molecules, the allosteric substrate specificity site and a conserved but previously unseen flap over the active site. Taken together, the results suggest that dATP inhibition in anaerobic RNRs acts by increasing the flexibility of the flap and GRD, thereby preventing both substrate binding and radical mobilisation.

Photochemical Initiation and Reactions of Thiyl Radicals Studied with SH2' Radical Traps.

A radical trapping method based on an SH2' homolytic substitution reaction was applied to study the mechanism of a photochemical spirocyclisation of indole-ynones in the presence of thiols. Starting material, products and a range of trapped radical intermediates were simultaneously detected in reaction mixtures by mass spectrometry (MS). The trapped intermediates included both initiating and main chain propagating radicals. These data made it possible to propose a self-initiation mechanism consistent with the originally postulated photoexcitation of an intramolecular electron donor-acceptor complex of the substrate. The effect of thiol structure on the MS peak intensity of the reaction components was rationalised in terms of the relative stability of the radical intermediates. The results were compared to a simpler related reaction, a photochemical thiol-ene addition where reagents, products and trapped intermediate radicals were also detected by MS. Relative MS peak intensities were again explained by a combination of electronic and steric effects on the stability of intermediate radicals. Overall, SH2' radical trapping was demonstrated to be a powerful experimental technique for providing mechanistic evidence on photochemical and other organic radical reactions.

Stable Radical Isoporphyrin Copolymer Prepared with Di(phenylphosphane).

Two diphosphanes with variable-length ligands tested as nucleophiles to prepare isoporphyrin copolymers in the presence of ditolylporphyrin of zinc (ZnT2P) prevented the oxidation of the diphosphine ligand. This paper demonstrates the power of this approach and describes the photoelectrocatalytic properties. The obtained copolymers were characterized by UV-vis spectroscopy, X-ray photoelectron spectroscopy, atomic force micrograph (AFM), EQCM (Electrochemical Quartz Cristal Microbalance) and electrochemistry. Their impedance properties (EIS) were studied and their photovoltaic performances were also investigated by photocurrent transient measurements under visible light irradiation.

Organophotocatalyzed Cross Coupling of C- and Si-Radical to Access Dibenzylic Silanes from para-Quinone Methides and Silanecarboxylic Acids.

Herein we present a catalytic cross-coupling strategy between C-radicals and Si-radicals, enabling the efficient, gentle, and versatile synthesis of dibenzylic silanes from para-quinone methides and silanecarboxylic acids as the stable silyl radical precursors. The reaction is facilitated by an inexpensive organophotocatalyst and exhibits broad compatibility with various electron-donating and electron-withdrawing functional groups. Notably, mechanistic investigations suggest the involvement of dibenzylic and silyl radicals, underscoring a novel radical coupling mechanism that introduces a fresh perspective on C-Si bond formation.

Synthesis and pharmacological evaluation of novel N-aryl-cinnamoyl-hydrazone hybrids designed as neuroprotective agents for the treatment of Parkinson’s disease

Molecular hybridization between structural fragments from the structures of curcumin (1) and resveratrol (2) was used as a designing tool to generate a new N-acyl-cinnamoyl-hydrazone hybrid molecular architecture. Twenty-eight new compounds were synthesized and evaluated for multifunctional activities related to Parkinson’s disease (PD), including neuroprotection, antioxidant, metal chelating ability, and Keap1/Nrf2 pathway activation. Compounds 3b (PQM-161) and 3e (PQM-164) were highlighted for their significant antioxidant profile, acting directly as induced free radical stabilizers by DPPH and indirectly by modulating intracellular inhibition of t-BOOH-induced ROS formation in neuronal cells. The mechanism of action was determined as a result of Keap1/Nrf2 pathway activation by both compounds and confirmed by different experiments. Furthermore, compound 3e (PQM-164) exhibited a significant effect on the accumulation of α-synuclein and anti-inflammatory activity, leading to an expressive decrease in gene expression of iNOS, IL-1β, and TNF-α. Overall, these results highlighted compound 3e as a promising and innovative multifunctional drug prototype candidate for PD treatment.

Stable Radicals in Dihydrophenazine Derivatives-Doped Epoxy Resin for High Photothermal Conversion.

Organic radicals exhibit great potential in photothermal applications, however, their innate high reactivity with oxygen renders the preparation of stable organic radicals highly challenging. In this work, a series of co-doped radical polymers ares prepared by doping dihydrophenazine derivatives (DPPs) into the epoxy resin matrix. DPPs can form radical species through the electron transfer process, which are further stabilized by the complex 3D network structure of epoxy resin. Experimental results show that the photothermal conversion efficiency is as high as 79.9%, and the temperature can quickly rise to ≈130°C within 60 s. Due to the excellent visible light transmittance and mechanical properties of co-doped systems, this study further demonstrates their practical applications in energy-saving solar windows and thermoelectric power generation.

Modulation of the Human Erythrocyte Antioxidant System by the 5- and 6-Membered Heterocycle-Based Nitroxides.

Nitroxides are stable radicals consisting of a nitroxyl group, >N-O•, which carries an unpaired electron. This group is responsible for the paramagnetic and antioxidant properties of these compounds. A recent study evaluated the effects of pyrrolidine and pyrroline derivatives of nitroxides on the antioxidant system of human red blood cells (RBCs). It showed that nitroxides caused an increase in the activity of superoxide dismutase (SOD) and the level of methemoglobin (MetHb) in cells (in pyrroline derivatives) but had no effect on the activity of catalase and lactate dehydrogenase. Nitroxides also reduced the concentration of ascorbic acid (AA) in cells but did not cause any oxidation of proteins or lipids. Interestingly, nitroxides initiated an increase in thiols in the plasma membranes and hemolysate. However, the study also revealed that nitroxides may have pro-oxidant properties. The drop in the AA concentration and the increase in the MetHb level and in SOD activity may indicate the pro-oxidant properties of nitroxides in red blood cells.

Phenyl Derivatives Modulate the Luminescent Properties and Stability of CzBTM-Type Radicals

The distinctive electron structures of luminescent radicals offer considerable potential for a diverse array of applications. Up to now, the luminescent properties of radicals have been modulated through the introduction of electron-donating substituents, predominantly derivatives of carbazole and polyaromatic amines with more and more complicated structures and redshifted luminescent spectra. Herein, four kinds of (N-carbazolyl)bis(2,4,6-tirchlorophenyl)-methyl (CzBTM) radicals, Ph2CzBTM, Mes2CzBTM, Ph2PyIDBTM, and Mes2PyIDBTM, were synthesized and characterized by introducing simple phenyl and 2,4,6-trimethylphenyl groups to CzBTM and PyIDBTM. These radicals exhibit rare blueshifted emission spectra compared to their parent radicals. Furthermore, modifications to CzBTM significantly enhanced the photoluminescence quantum yields (PLQYs), with a highest PLQY of 21% for Mes2CzBTM among CzBTM-type radicals. Additionally, the molecular structures, photophysical properties of molecular orbitals, and stability of the four radicals were systematically investigated. This study provides a novel strategy for tuning the luminescent color of radicals to shorter wavelengths and improving thermostability.

1-Ethyl-3-methylimidazolium Acetate as a Reactive Solvent for Elemental Sulfur and Poly(sulfur nitride).

We investigate the reactive dissolution process of poly(sulfur nitride) (SN)x in the ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate [EMIm][OAc] in comparison to the process of elemental sulfur in the same IL. It has been known from the literature that during the reaction of S8 with [EMIm][OAc], the respective thione is formed via a radical mechanism. Here, we present new results on the kinetics of the formation of the respective imidazole thione (EMImS) via the hexasulfur dianion [S6]2- and the trisulfur radical anion [S3]•-. We can show that [S6]2- is formed first, which dissociates then to [S3]•-. Also, long-term stable radicals occur, which are necessary side products provided in a reaction scheme. During the reaction of [EMIm][OAc] with (SN)x chains, two further products can be identified, one of which is the corresponding imine. The reactions are followed by time-resolved NMR spectroscopic methods that showed the corresponding product distributions and allowed the assignment of the individual signals. In addition, continuous-wave (CW) EPR and UV/vis spectroscopic measurements show the course of the reactions. Another significant difference in both reactions is the formation of a long-term stable radical in the sulfur-IL system, which remains active over 35 days, while for the (SN)x-IL system, we can determine a radical species only with the spin trap 5,5-dimethyl-1-pyrrolin-N-oxide, which indicates the existence of short-living radicals. Since the molecular dynamics are restricted based on the EPR spectra, these radicals must be large.

Robust Radicals Featuring B- and N-Embedded Dioxygen-Bridged Units: Synthesis, Structures, and Optical Properties.

Tris(2,4,6-trichlorophenyl)methyl (TTM) group has been widely used for constructing organic radicals, but the poor optical stabilities limit the application prospects of the TTM radicals. In this work, the rigid B- and N-embedded dioxygen-bridged (BO and NO) units were attached to the TTM skeleton as the strong electron-withdrawing and electron-donating groups, respectively. The rigidity and strong electronic effect of the BO and NO units contribute to the high chemical and optical stability of BO-TTM and NO-TTM radicals. Notably, NO-TTM exhibits near-infrared emission at 830 nm with a narrow full width at half maximum (FWHM) of 55 nm (100 meV), while BO-TTM shows blue-shifted luminescence at 635 nm and a narrower FWHM of merely 43 nm (130 meV). This study has developed a methodology to produce highly efficient and enduring luminescent radicals, which could tune emission properties such as wavelength and FWHM.

The paradigm of magnetic molecule in quantum matter: Slow molecular spin relaxation

The quantum nature of single-ion magnets, single-molecule magnets, and single-chain magnets has been manifested among other phenomena by magnetic hysteresis due to slow spin relaxation, competing with fast quantum tunneling at low temperatures. Slow spin relaxation, described by Arrhenius-type law with the effective barrier energies Ueff = 50 cm–1, was discovered 3 decades ago in paramagnetic Mn12-acetate complex of oxy-bridged mixed-valence manganese ions, below the blocking temperature TB = 3 K. In contrast to common magnetic materials, it is governed primarily by magnetic anisotropy, set by zero-splitting of spin states of a magnetic ion in a field of ligands, and spin-lattice coupling. The emerging studies on the border of coordination chemistry, physics of spin systems with reduced dimensionality, and nanotechnologies, were performed in search of routes for enhancement of Ueff and TB characteristics, in line with increase of operation temperature and quantum correlation time, mandatory for quantum applications. The best results with TB ∼ 80 K and Ueff ∼ 1261 cm–1, were obtained for DyIII single-ion magnet, so far. Numerous excellent research and review articles address particular activities behind this achievement. It follows, that present challenges are dictated by the rational development of novel, smart magnetic molecules, featured by butterfly cores, cyano-bridges, 2D metal-organic frameworks, and metal-free graphene nanoclusters, as well as stable free radicals, magnetized by spare electrons. These species are briefly considered here with respect to the unique experience of international collaborative activity, established by Prof. Juan Bartolomé.

Specificity of Photochemical Energy Conversion in PhotosystemI from the Green Microalga Chlorella ohadii.

Primary excitation energy transfer and charge separation in photosystemI(PSI) from the extremophile desert green alga Chlorella ohadii grown in low light were studied using broadband femtosecond pump-probe spectroscopy in the spectral range from 400 to 850nm and in the time range from 50fs to 500ps. Photochemical reactions were induced by the excitation into the blue and red edges of the chlorophyll Qy absorption band and compared with similar processes in PSI from the cyanobacterium Synechocystissp. PCC6803. When PSI from C.ohadii was excited at 660nm, the processes of energy redistribution in the light-harvesting antenna complex were observed within a time interval of up to 25ps, while formation of the stable radical ion pair P700+A1- was kinetically heterogeneous with characteristic times of 25 and 120ps. When PSI was excited into the red edge of the Qy band at 715nm, primary charge separation reactions occurred within the time range of 7ps in half of the complexes. In the remaining complexes, formation of the radical ion pair P700+A1- was limited by the energy transfer and occurred with a characteristic time of 70ps. Similar photochemical reactions in PSI from Synechocystis6803 were significantly faster: upon excitation at 680nm, formation of the primary radical ion pairs occurred with a time of 3ps in ~30% complexes. Excitation at 720nm resulted in kinetically unresolvable ultrafast primary charge separation in 50% complexes, and subsequent formation of P700+A1- was observed within 25ps. The photodynamics of PSI from C.ohadii was noticeably similar to the excitation energy transfer and charge separation in PSI from the microalga Chlamydomonas reinhardtii; however, the dynamics of energy transfer in C.ohadii PSI also included slower components.

Evaluation of the Antioxidant Activity of Matricaria chamomilla L. and Identification of Chemical Compounds by GC-MS Technology

The aim of the present study was the preparation of Chamomilla extract in different solvents (water, ethanol and hexane) and the determination of the active compounds in Matricaria chamomilla L extracts by using GC-MS analyses. and studying their biological activity as antioxidants using DPPH. A stable free radical is widely used to assess the free radical scavenging activity of antioxidant compounds. The yield of the final product was 26.5% aqueous extract, 19.5% ethanoic extract and 12.5% hexan extract. The result showed a significant decrease in percentage inhibition in hexane extract and a significant increase in aqueous and ethanol extracts. This study's findings, taken as a whole, proved beyond a reasonable doubt that chamomile is a valuable medical herb. that contains phenolic, flavonoids, esters and other compounds in a high ratio in aqueous extract, as shown by GC-MS analyses and that it appears to have a high power of antioxidant activity. Chamomile provides potential anti-oxidant, anti-inflammatory and anti-cancer treatments.

Furan-oxadiazole hybrids as promising antioxidants: Synthesis, characterization, ADME and molecular docking studies on peroxiredoxin-2

The study involves the synthesis and characterization of a novel series of furan-based compounds 1–9 incorporating strategic modifications with isatin, pyrazole, and oxadiazole motifs. The synthesized compounds were characterized and assigned with different spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and mass spectra. Antioxidant screening assays using the DPPH radical scavenging method revealed that the oxadiazole derivative 9 exhibited exceptional antioxidant activity, with an EC50 value of 0.0038 mM, attributed to the oxadiazole ring's favourable electron delocalization and radical stabilization properties. Molecular docking simulations with the Peroxiredoxin-2 (Prdx-2) crystal structure (PDB: 5IJT) predicted favourable binding interactions for the synthesized compounds, with docking scores ranging from -6.1629 to -7.9878 kcal/mol. The sugar moieties facilitated hydrogen bonding interactions with key active site residues, while the furan and phenyl rings contributed to π-hydrogen interactions. Furthermore, in silico ADME prediction studies assessed the drug-likeness and pharmacokinetic properties of the compounds, identifying promising lead candidates for further optimization and development as potential antioxidant therapeutics targeting Prdx-2.

Synthesis and Antioxidant Activity of N-Benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine Oxides.

The synthesis, antioxidant capacity, and anti-inflammatory activity of four novel N-benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine oxides 10a-d are reported herein. The nitrones 10a-d were tested for their antioxidant properties and their ability to inhibit soybean lipoxygenase (LOX). Four diverse antioxidant tests were used for in vitro antioxidant assays, namely, interaction with the stable free radical DPPH (1,1-diphenyl-2-picrylhydrazyl radical) as well as with the water-soluble azo compound AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride), competition with DMSO for hydroxyl radicals, and the scavenging of cationic radical ABTS•+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation). Nitrones 10b, 10c, and 10d, having the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, exhibited high interaction with DPPH (64.5-81% after 20 min; 79-96% after 60 min), whereas nitrone 10a with unfunctionalized phenyl group showed the lowest inhibitory potency (57% after 20 min, 78% after 60 min). Nitrones 10a and 10d, decorated with phenyl and 4-fluoro-3-methylphenyl motif, respectively, appeared the most potent inhibitors of lipid peroxidation. The results obtained from radical cation ABTS•+ were not significant, since all tested compounds 10a-d showed negligible activity (8-46%), much lower than Trolox (91%). Nitrone 10c, bearing the 2,4-difluorophenyl motif, was found to be the most potent LOX inhibitor (IC50 = 10 μM).

Correlation between Radical and Quartet State Coherence Times in Photogenerated Triplet-Radical Conjugates.

Molecular quartet states, generated by photoexcitation of chromophore-radical conjugates, have been shown to exhibit attractive properties for applications in the field of molecular spintronics. Many of these applications, such as quantum sensing, require a coherent manipulation of the spin system, implying the need to control the quartet state spin coherence properties. By examining the influence of structural and matrix-related factors, we demonstrate a correlation between the coherence decay of the photogenerated quartet state and that of the tethered stable radical, paving the way for a rational design of photogenerated molecular three-spin systems with optimized coherence properties.

Confinement-enhanced stabilization and enrichment of hydroxyl radicals within Ni-based metal–organic frameworks for radiation-self-Fenton degradation of dye pollutants

Confinement-enhanced stabilization and enrichment of hydroxyl radicals within Ni-based metal–organic frameworks for radiation-self-Fenton degradation of dye pollutants