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Study of the segmental mobility of polymer chains is important when the polymer is used as drag reduction agents of crude oil. Electron spin resonance (ESR) spectroscopy can provide important information about segmental dynamics of polymer chains, which is related to their microenvironment. In this article, we employed an amphiphilic polymer to study the effect of hydrophilic/hydrophobic balance of the polymers on the segmental motion of polymer chains. Poly(styrene-co-maleic acid) (PSMA) was spin labeled with 4-amino TEMPO radicals by increasing the concentration of radical moiety on the polymer chains. The PSMA and spin labeled-PSMAs (SL-PSMAs) were characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) spectroscopy, Cyclic voltammetry (CV) and ESR techniques. Inter-polymer complexes (IPCs) of SL-PSMA-2 were prepared by employing polyethylene glycols (PEGs) of varying molecular weights. The results showed that the increased hydrophobic interactions of nitroxide radicals on the SL-PSMAs’ chains reduced the rotational mobility of spin labels and the random coil-to-globular transition of polymer chains occurred at higher pH value for SL-PSMAs, which showed a slow motion component in the ESR spectra of SL-PSMAs. Further, by increasing the molecular weight of PEGs in IPCs the complexation was increased, which also reduced the rotational motion of spin labels due to interpolymer hydrogen bonding causing a slow motion component in the ESR spectra.

The oxidative damage of DNA is associated with aging and the development of various diseases. Although nucleoside-derived radicals play an important role in DNA oxidation, their analysis methods are limited. Herein, we propose a fluorometric detection and structural analysis of radicals on the surface of oxidatively damaged DNA using a profluorescent nitroxide probe combined with liquid chromatography-fluorometry and high-resolution tandem mass spectrometry.

To explore the effect of different positions and number of pyrrolidine bound to the carbon cage on the stabilization effect of fulleropyrrolidine derivatives to nitrocellulose (NC)/nitroglycerine (NG), we synthesized N-(4-methoxy) phenylpyrrolidine-C60 and four different of bis(N-(4-methoxy) phenylpyrrolidine)-C60 compounds through Prato reaction. Their structures were characterized by UV–vis, 1H NMR, 13C NMR, high-resolution mass spectroscopy, and single-crystal X-ray diffraction. Their stabilization effect to NC/NG were investigated using differential scanning calorimetry, methyl violet, vacuum stabilization effect, weight loss, and accelerating rate calorimeter tests. The results indicated these compounds had excellent stabilization effect to NC/NG. The stabilization effect of the fulleropyrrolidine bisadducts to NC/NG is significantly better than that of fulleropyrrolidine monoadduct and C60. Moreover, the position where pyrrolidine binds to fullerene in fulleropyrrolidine bisadducts is different, and its stabilization effect to NC is also different. The stabilization effect order of different bisadduct isomers to nitrocellulose is as follows: e-edge > trans-2> cis-2> trans-3. Electron paramagnetic resonance (EPR) and FT-IR were used to study the stabilization mechanism of fulleropyrrolidine derivatives to NC/NG. The EPR results also show that fulleropyrrolidine bisadducts with different addition sites have different abilities to absorb nitroxide, and their ability is better than that of the monoadduct and C60, which is consistent with the results of stabilization effect performance test.

Pairing the spectral resolution provided by high magnetic fields at ambient temperature with the enhanced sensitivity offered by dynamic nuclear polarization (DNP) is a major goal of modern solid-state NMR spectroscopy, which will allow one to unlock ever-challenging applications. This study demonstrates that, by combining HyTEK2, a hybrid BDPA-nitroxide biradical polarizing agent, with ortho-terphenyl (OTP), a rigid DNP matrix, enhancement factors as high as 65 can be obtained at 230 K, 40 kHz magic angle spinning (MAS), and 18.8 T. The temperature dependence of the DNP enhancement and its behavior around the glass transition temperature (Tg) of the matrix is investigated by variable-temperature EPR measurements of the electron relaxation properties and numerical simulations. A correlation is suggested between the decrease in enhancement at the passage of the Tg and the concomitant drop of both transverse electron relaxation times in the biradical.

Nitroxide spin probes and spin labels are broadly utilized in EPR oximetry studies ranging from in vivo investigation to profiling heterogeneous environment of lipid bilayer membranes and proteins by site-specific oxygen-accessibility experiments. In such experiments, effective collision distances of the spin exchange interaction between the nitroxide and molecular oxygen are typically assumed to be the same even though localization of spin density over the nitroxide moiety is known to be affected by local polarity. Furthermore, some biophysical studies, such as those involving lipid bilayers, are often carried out with structurally different nitroxides but the results are analyzed under an assumption that proportionality between changes in the nitroxide electronic relaxation times and the product of the local oxygen concentration and translational diffusion coefficients remain the same. Here, we present an experimental verification of such a prevailing but not yet verified assumption by measuring effects of molecular oxygen in air and pure oxygen at atmospheric pressure on continuous wave EPR spectra of six structurally different nitroxides including those capable of reversible protonation. The data were analyzed using a convolution fitting model, which, by comparing EPR spectra measured at two different oxygen concentrations, allows one to extract the peak-to-peak width $${\Delta }B_{{{\text{p}} - {\text{p}}}}$$ of a Lorentzian function that characterizes the effect of oxygen broadening. While the data on oxygen broadening measured by comparing EPR spectra of nitroxide solutions equilibrated with nitrogen and pure oxygen show clear trends that are rationalized by differences in the nitroxide structure, the overall variations in $${\Delta }B_{{{\text{p}} - {\text{p}}}}$$ for various nitroxides fall within ca. ± 5%. Such variations are comparable to the effect of “salting-out” of molecular oxygen in aqueous solutions when electrolytes are present in physiological concentrations. Overall, the data further establish nitroxides as robust EPR molecular probes to measure the product of local oxygen concentration and its translational diffusion coefficient under a wide range of conditions such as pH and electrolyte concentrations.

Nitroxide-mediated polymerization (NMP) allows one to synthesize well-defined polymers with narrow molar mass distribution (MMD) and latent functionality. For acrylates, however, side reactions, such as backbiting and beta-scission and increases in viscosity, can complicate the molecular control, affecting the MMD dispersity, the double bound content, and the degree of livingness. On top of this, acrylate polymerizations are highly exothermic and thus dedicated temperature control is recommended, even under general lab-scale NMP conditions. In the present work, we account for both side reactions, diffusional limitations and nonisothermicity, so that a detailed model-based design for NMP of n-butyl acrylate can be performed in view of a better evaluation of its commercial potential. The relevance of temperature control and semibatch feeding strategies is particularly explored, benefiting from (i) a successful benchmark to NMP lab-scale batch literature data and (ii) a previous successful benchmark under various lab-scale free radical polymerization (FRP) conditions. It is showcased that specific set points of NMP characteristics, e.g., polymerization time, number average molar mass, and unsaturation level, can be achieved for a high monomer conversion by realizing less conventional thus nonlinear number average molar mass profiles, which is highly relevant for the polymer synthesis and reaction engineering community. The current work, which puts forward a dedicated research strategy from FRP to NMP to minimize error on kinetic parameter determination steps, opens the pathway to maximize the potential of reversible deactivation radical polymerization techniques for their more elegant implementation and appreciation in the society.

TEMPOL nitroxide radicals are frequently used as a polarizing agent for liquid-state Overhauser dynamic nuclear polarization. To achieve large signal enhancements at high magnetic fields (9.4 T), f...

The membrane transporter BtuB is site-directedly spin labelled on the surface of living Escherichia coli via Diels–Alder click chemistry of the genetically encoded amino acid SCO-l-lysine. The previously introduced photoactivatable nitroxide PaNDA prevents off-target labelling, is used for distance measurements, and the temporally shifted activation of the nitroxide allows for advanced experimental setups. This study describes significant evolution of Diels–Alder-mediated spin labelling on cellular surfaces and opens up new vistas for the the study of membrane proteins., The membrane transporter BtuB is site-directedly spin labelled on the surface of living bacteria via Diels–Alder click chemistry.

To investigate the capability of π-π stacking motifs to enable spin-spin coupling, we designed and synthesized three pairs of regio-isomers featuring two radical moieties joined by a [2.2]paracyclophane (CP) unit. By fusing indeno units to CP, two partially stacked fluorene radicals are covalently linked, exhibiting evident antiferromagnetic (AFM) coupling regardless of the orientation of two spins. Remarkably, while possessing high diradical indices of 0.8 and 0.9, the two molecules demonstrate good air stability by virtue of their singlet ground state. Single crystals help unravel the structural basis of their AFM coupling behaviors. When two radical centers are arranged at the pseudometa-positions around CP, the face-to-face stacked phenylene rings intrinsically confer orbital interactions that promote AFM coupling. On the other hand, if two radicals are directed in the pseudopara-orientation, significant orbital overlapping is observed between the radical centers (i.e., C9 of fluorene) and the aromatic carbons laid on the side, rendering AFM coupling between the two spins. In contrast, when two fluorene radicals are tethered to CP via C9 through a single C-C bond, ferromagnetic (FM) coupling is manifested by both diradical isomers featuring pseudometa- and pseudopara-connectivity. With minimal spin distributed on CP and thus limited contribution from π-π stacking, their spin-spin coupling properties are more similar to a pair of nitroxide diradical analogues, in which the two spins are dominantly coupled via through-space interactions. From these results, important conclusions are elucidated such as that although through-space interactions may confer FM coupling, with weakened strength shown by PAH radicals due to their lower polarity, face-to-face stacked π-frameworks tend to induce AFM coupling, because favorable orbital interactions are readily achieved by PAH systems hosting delocalized spins that are capable of adopting varied stacking motifs.

Nitroxide compounds have been used as redox-sensitive imaging probes by electron paramagnetic resonance (EPR) for assessing oxidative stress in vivo. Fast redox reactions of nitroxide radicals are favorable for assessment of higher redox sensitivity; however, a variety of nitroxides have not been trialed for use as imaging probes due to their very rapid in vivo reduction, which cannot be captured at the slow operation speed of existing EPR imagers. To overcome this limitation, we improved our EPR system to provide a stable and highly sensitive imaging operation. We challenged the improved EPR imager to perform three-dimensional (3D) EPR imaging of mouse brain using two useful nitroxide imaging probes, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) and 2,6-dispiro-4',4"-dipyrane-piperidine-4-one-N-oxyl (DiPy). The second-order rate constant of DiPy with ascorbic acid is 10 times larger than that of Tempol. The improved EPR imager obtained clear 3D EPR images of mouse brain and demonstrated that Tempol could exist with an unpaired electron. The imager also successfully obtained 3D EPR images of mouse head after administration of DiPy. As 126 projections can be acquired in a period of 6 s, 3D EPR imaging can visualize the sequential process of DiPy entering the brain, being distributed within the brain, and being reduced within the brain. These improvements to the EPR imager will enable useful nitroxide imaging probes that were previously unsuitable as imaging probes due to their rapid reduction to be considered for use for sensitive redox assessment in an in vivo system.

This study describes the adsorption of free radical TEMPO onto Al2O3 nanoparticles in the solvents with different polarities including DMF, methanol, acetone, THF, petroleum ether and n-hexane at ambient temperature to evaluate the radical scavenging activity. The adsorption percentage of radical is calculated by measuring the maximum adsorption intensity of the ultraviolet (UV) absorption spectrum of TEMPO in the presence and the absence of Al2O3 nanoparticles. The morphology of Al2O3 nanoparticles before and after adsorption of TEMPO is studied using transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared (FT-IR) spectroscopy. The adsorption energy and other thermochemical data for the adsorption of TEMPO over different active sites of Al2O3 are estimated via dispersion corrected density functional theory (DFT + Disp). The donor-acceptor interactions between Al2O3 and TEMPO are calculated using natural bond orbital (NBO) theory. It is found that Al2O3 nanoparticles have efficient radical scavenging activity (RSA) in the range of 50-72%. Approximately, a linear relationship between dielectric constant of solvent and the absorption percentage of TEMPO over Al2O3 nanoparticles is achieved. So that with decreasing the polarity of solvent, the adsorption of TEMPO onto Al2O3 nanoparticles is increased. The adsorption of TEMPO over Lewis acidic sites of Al2O3 is more favored than Bronsted acidic and basic sites. The comparison between experimental and calculated IR spectra of TEMPO/Al2O3 complexes provides the good evidence for adsorption of TEMPO onto the surface of Al2O3 nanoparticles.

A series of branched high-molecular-weight alkoxyamines (HAAs) based on polystyrene of different molecular weight were synthesized using nitroxide radicals generated in situ in the presence of conjugated dinitrones (N,N-dimethylglyoxaldinitrone, N,N-di-tert-butylgly-oxaldinitrone, and N,N-diphenylglyoxaldinitrone). Structural features of the products obtained were studied by MALDI-TOF mass spectrometry. Modification of the synthesized HAAs in the presence of azobisisobutyronitrile, carbon tetrabromide, dodecyl mercaptane, 4,5,5-trimethyl-2,2-diethyl-2,5-dihydroimidazole-1-oxyl, and 3,5-di-tert-butylbenzoquinone, as well as thermolysis of the HAAs in the presence of atmospheric oxygen showed that the nitroxide fragments are located within the polymer chain irrespective of the initial structure of the conjugated dinitrone. The molecular weight characteristics and conformational properties of the nitroxide-containing linear macromolecules and polymers were studied by static and dynamic light scattering and by viscometry. In most cases, the calculated values of the ρ-parameter (Rg/Rh) and the Zimm viscosity factor of the branched polystyrene samples synthesized using conjugated dinitrones are lower than those of linear analogues.

Synthesis of bis-spiro-oxetane and bis-spiro-tetrahydrofuran pyrroline nitroxide radicals relies on the Mitsunobu reaction-mediated double cyclizations of N-Boc protected pyrroline tetraols. Structures of the nitroxide radicals are supported by X-ray crystallography. In a trehalose/sucrose matrix at room temperature, the bis-spiro-oxetane nitroxide radical possesses electron spin coherence time, Tm ≈ 0.7 μs. The observed enhanced Tm is most likely associated with strong hydrogen bonding of oxetane moieties to the trehalose/sucrose matrix.

In this work, we investigated the redox transients of a number of water-soluble spin labels upon their interactions with Photosystem II (PS II) core complexes isolated from spinach leaves. We have found that the reactivity of nitroxide radicals, determined by the rate of their reduction upon illumination of PS II, depends on the chemical structure of radicals and the capability of their coming close to low-potential redox centers of photoactive PS II complexes. An enhanced capability of nitroxide radicals to accept electrons from PS II correlates with their chemical structure. Nitroxide radicals NTI (2,2,5,5-tetramethyl-4-nitromethylene-3-imidazolidine-N-oxyl) and Tacet (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl-acetate), containing polar groups, appear to be most efficient acceptors of electrons donated by PS II compared to neutral (TEMPOL, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) or positively charged (Tamine, 4-amino-2,2,6,6-tetramethylpiperidine-l-oxyl) spin labels. We assume that enhanced reactivities of polar nitroxide radicals, NTI and Tacet, are determined (1) by their relatively high redox potentials, providing the possibility to accept electrons from PS II, and (2) by their affinities to the closest binding sites on the surface of PS II in the vicinity of the primary plastoquinone acceptor PQA (12–14 Å) or/and in the intraprotein cavity for the secondary plastoquinone PQB (~ 22 Å).

Methano[60]fullerenes with two and four nitroxide radicals are studied by EPR spectroscopy. It is shown that nitroxide derivatives of fullerene C60 undergo conformational changes in liquid solution. It is established that transitions between the two conformations take place in the case of the biradical adduct of C60 fullerene. For the tetraradical adduct in the trans-3 position, it is shown that the biradicals do not interact and behave independently; therefore, the two-conformational model provides a good description of the experimental data. A more complicated situation is implemented for the tetraradical adduct in the equatorial position. The biradicals are not independent for this system, and their interaction leads to an increase in the number of possible conformations. Thermodynamic parameters for these systems are calculated.

Solution-based syntheses are omnipresent in chemistry but are often associated with obvious disadvantages, and the search for new mild and green synthetic methods continues to be a hot topic. Here, comparative studies in four different reaction media were conducted, that is, the solid-state mechano- and slow-chemistry synthesis, melted phase, and solution protocols, and the impact of the employed solvent-free solid-state versus liquid-phase synthetic approaches was highlighted on a pool of products. A moderately exothermic model reaction system was chosen based on bis(pentafluorophenyl)zinc, (C6 F5 )2 Zn, and 2,2,6,6-tetramethylpiperidinyl oxide (TEMPO) as a stable nitroxyl radical, anticipating that these reagents may offer a unique landscape for addressing kinetic and thermodynamic aspects of wet and solvent-free solid-state processes. In a toluene solution two distinct paramagnetic Lewis acid-base adducts (C6 F5 )2 Zn(η1 -TEMPO) (1) and (C6 F5 )2 Zn(η1 -TEMPO)2 (2) equilibrated, but only 2 was affordable by crystallization. In turn, crystallization from the melt was the only method yielding single crystals of 1. Moreover, the solid-state approaches were stoichiometry sensitive and allowed for the selective synthesis of both adducts by simple stoichiometric control over the substrates. Density functional theory (DFT) calculations were carried out to examine selected structural and thermodynamic features of the adducts 1 and 2. Compound 2 is a unique non-redox active metal complex supported by two nitroxide radicals, and the magnetic studies revealed weak-to-moderate intramolecular antiferromagnetic interactions between the two coordinated TEMPO molecules.

The structures of low-molecular-weight chitosan oligomers and their two nitroxide derivatives were examined using the force field molecular dynamics (MD) and density functional theory calculations with implicit and explicit solvent models. Rotamers of both neutral oligomers and those protonated at amino group were determined and the influence of the chain length and solvent (water) on their stability was studied. Bent conformations of the chitosan chain were found to be the most stable in the gas phase, whereas a linear structure of the polysaccharide is more preferred in water. Conformational transitions between the bent structures can occur only via the linear conformation of chitosan. According to the MD calculations, the nitroxides linked at the amino group do not form intramolecular hydrogen bonds with polar groups of the polysaccharide. The nitroxide substituents enhance the conformational flexibility of chitosan, but the linear conformation of the substituted oligomers remains most populated in water.

Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) has enabled promising applications in spectroscopy and imaging, but remains poorly widespread due to experimental complexity. Broad democratization of dDNP could be realized by remote preparation and distribution of hyperpolarized samples from dedicated facilities. Here we show the synthesis of hyperpolarizing polymers (HYPOPs) that can generate radical- and contaminant-free hyperpolarized samples within minutes with lifetimes exceeding hours in the solid state. HYPOPs feature tunable macroporous porosity, with porous volumes up to 80% and concentration of nitroxide radicals grafted in the bulk matrix up to 285 μmol g−1. Analytes can be efficiently impregnated as aqueous/alcoholic solutions and hyperpolarized up to P(13C) = 25% within 8 min, through the combination of 1H spin diffusion and 1H → 13C cross polarization. Solutions of 13C-analytes of biological interest hyperpolarized in HYPOPs display a very long solid-state 13C relaxation times of 5.7 h at 3.8 K, thus prefiguring transportation over long distances., Hyperpolarization by dissolution dynamic nuclear polarization has brought highly sensitive magnetic resonance to reality but there still remains severe limitations. Here the authors show an approach relying on the generation of hyperpolarizing polymers that bear a dual function.

In our previous work [Edeleva et al. Chem. Commun. 2019, 55, 190-193], we proposed a versatile approach to the activation of the homolysis of an aldonitrone group-containing alkoxyamine by 1,3-dipolar cycloaddition to a vinyl monomer. Both nitroxide- and alkoxyamine-containing aldonitrones were found to be capable of reacting with the activated alkenes. In the present study, the kinetics of these reactions with 11 different vinyl monomers were investigated using EPR and NMR spectroscopy, and apparent activation energies as well as pre-exponential factors were determined. The influence of monomer structure on the rate of the 1,3-dipolar cycloaddition is discussed. For the vinyl monomers typically used in nitroxide mediated polymerization (styrene, methyl methacrylate) the rate coefficient of cycloaddition to the nitroxide is around k(353 K) ∼4 ⋅ 10-4 L mol-1 s-1 , whereas for n-butyl acrylate and methyl vinyl ketone we observed the fastest cycloaddition reaction with k(353 K)=8 ⋅ 10-3 and 4 ⋅ 10-2 L mol-1 s-1 respectively.

EPR line shapes in fluid solution and electron spin relaxation times and lineshapes in frozen solution were measured at X-band for two dinitroxides. For dinitroxide 1, which has two proxyl nitroxides connected by an amide linkage, the fluid solution spectra are in the strong exchange limit (J >> nitrogen hyperfine coupling) and the interspin distance in glassy water:glycerol is about 8.8 A. For dinitroxide 2, which has two proxyl nitroxides connected by a bridging ethylenediamine and two amide linkages, the fluid solution spectra are characteristic of dynamic exchange between conformations with strong exchange (J > 850 MHz) and conformations with weaker exchange interaction. For 2, the interspin distance in glassy water:glycerol is about 9.2 A and J > 600 MHz. T1 and Tm for both dinitroxides in 1:1 water:glycerol were measured at 10 to 160 K. Relaxation times are within experimental uncertainty of values for a pyrrolinoxyl monoradical and very similar to values for a nitroxide with a piperidinyl ring. These data demonstrate that even for these relatively flexible linkages dipolar interaction with an interspin distance of about 9 A does not provide an effective spin–lattice relaxation mechanism for dinitroxides in glassy water:glycerol.

It has been observed that acrylate monomers are very difficult to polymerize with the low cost nitroxide catalyst 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO). Therefore, costly acyclic nitroxides such as N-tert-butyl-N-(1-diethylphosphono-2,2-dimethyl)-N-oxyl, (SG1), 2,2,5-Trimethyl-4-phenyl-3-azahexane-3-nitroxide (TIPNO) and TIPNO derivatives have to be used for the polymerization of the acrylic acid derivatives. There are very few reports on the use of TEMPO-derivatives toward the polymerization of n-butyl acrylate. Generally different reducing agents viz. glucose, ascorbic acid, hydroxyacetone etc. have been used to destroy excess TEMPO during the polymerization reaction. The acrylate polymerizations fail in the presence of TEMPO due to the strong C–O bond formed between the acrylate chain end and nitroxide. To the best of our knowledge, no literature report is available on the use of TEMPO without reducing agent or high temperature initiators, toward the polymerization of n-butyl acrylate. The present study has been carried out with a view to re-examine the application of low cost nitroxide TEMPO, so that it can be utilized towards the polymerization of acrylate monomers (e.g. n-butyl acrylate). We have been able to polymerize n-butyl acrylate using the nitroxide TEMPO as initiator (via a macroinitiator). In this synthesis, a polystyrene macroinitiator was synthesized in the first step from TEMPO, after this TEMPO end-capped styrene macroinitiator (PSt-TEMPO) is used to polymerize n-butyl acrylate monomer. The amount of macroinitiator taken was varied from 0.05% to 50% by weight of n-butyl acrylate monomer. The polymerization was carried out at 120°C by bulk polymerization method. The experimental findings showed a gradual increase in molecular weight of the polymer formed and decrease in the polydispersity index (PDI) with increase in amount of PSt-TEMPO macroinitiator taken. In all experiments conversion was more than 80%. These results indicate that the polymerization takes place through controlled polymerization process. Effect of different solvents on polymerization has also been investigated. In the following experiments TEMPO capped styrene has been used as macroinitiator leading to the successful synthesis of poly n-Butyl acrylate. It has been found that styrene macroinitiator is highly efficient for the nitroxide mediated polymerization, even in very small concentration for the synthesis of poly n-butyl acrylate. High concentration of macroinitiator results in the formation of block copolymers of polystyrene and poly ( n-butyl acrylate) viz. polystyrene-block-poly-( n-butyl acrylate). The use of TEMPO toward controlled polymerization is of much importance, because it is the nitroxide commercially available at the lowest cost.

Herein, we report a novel strategy for introducing a luminophore into generic polymers facilitated by mechanical stimulation. In this study, polymeric mechanoradicals were formed in situ under ball-milling conditions to undergo radical-radical coupling with a prefluorescent nitroxide-based reagent in order to incorporate a luminophore into the polymer main chains via a covalent bond. This method allowed the direct and conceptually simple preparation of luminescent polymeric materials from a wide range of generic polymers such as polystyrene, polymethyl methacrylate, and polyethylene. These results indicate that the present mechanoradical coupling strategy may help to transform existing commodity polymers into more valuable functional materials.

A nitronyl nitroxide biradical with a capping N-donor group was discovered to improve single-molecule-magnet behavior of the Dy-biradical cluster, generating a magnetic reversal barrier of 146 K. As far as we know, the effective energy barrier of the Dy compound is largest in the nitronyl nitroxide 4f system by far.

This research was funded, in whole or in part, by the Wellcome Trust (099149/Z/12/Z and 204821/Z/16/Z). A CC BY or equivalent license is applied to the author-accepted manuscript arising from this submission, in accordance with the grant’s open-access conditions. B.E.B. and K.A. acknowledge support by the Leverhulme Trust (RPG-2018-397). J.L.W. was supported by the BBSRC DTP Eastbio. B.E.B. acknowledges equipment funding by BBSRC (BB/R013780/1). The study of ever more complex biomolecular assemblies implicated in human health and disease is facilitated by a suite of complementary biophysical methods. Pulse Dipolar electron paramagnetic resonance Spectroscopy (PDS) is a powerful tool that provides highly precise geometric constraints in frozen solution, however the drive towards PDS at physiologically relevant sub-μM concentrations is limited by the currently achievable concentration sensitivity. Recently, PDS using a combination of nitroxide and CuII based spin labels allowed measuring 500 nM concentration of a model protein. Using commercial instrumentation and spin labels we demonstrate CuII-CuII and nitroxide-nitroxide PDS measurements at protein concentrations below previous examples reaching 500 and 100 nM, respectively. These results demonstrate the general feasibility of sub-μM PDS measurements at short to intermediate distances (~1.5 - 3.5 nm), and are of particular relevance for applications where the achievable concentration is limiting. Postprint

MdfA from Escherichia coli is a prototypical secondary multi-drug (Mdr) transporter that exchanges drugs for protons. MdfA-mediated drug efflux is driven by the proton gradient and enabled by conformational changes that accompany the recruitment of drugs and their release. In this work, we applied distance measurements by W-band double electron-electron resonance (DEER) spectroscopy to explore the binding of mito-TEMPO, a nitroxide-labeled substrate analog, to Gd(III)-labeled MdfA. The choice of Gd(III)-nitroxide DEER enabled measurements in the presence of excess of mito-TEMPO, which has a relatively low affinity to MdfA. Distance measurements between mito-TEMPO and MdfA labeled at the periplasmic edges of either of three selected transmembrane helices (TM3101, TM5168, and TM9310) revealed rather similar distance distributions in detergent micelles (n-dodecyl-β- d -maltopyranoside, DDM)) and in lipid nanodiscs (ND). By grafting the predicted positions of the Gd(III) tag on the inward-facing (If) crystal structure, we looked for binding positions that reproduced the maxima of the distance distributions. The results show that the location of the mito-TEMPO nitroxide in DDM-solubilized or ND-reconstituted MdfA is similar (only 0.4 nm apart). In both cases, we located the nitroxide moiety near the ligand binding pocket in the If structure. However, according to the DEER-derived position, the substrate clashes with TM11, suggesting that for mito-TEMPO-bound MdfA, TM11 should move relative to the If structure. Additional DEER studies with MdfA labeled with Gd(III) at two sites revealed that TM9 also dislocates upon substrate binding. Together with our previous reports, this study demonstrates the utility of Gd(III)-Gd(III) and Gd(III)-nitroxide DEER measurements for studying the conformational behavior of transporters.

Macromolecular radicals, radical polymers, and polyradicals bear unique functionalities derived from their pendant radical groups. The increasing need for organic functional materials is driving the growth in research interest in macromolecular radicals for batteries, electronics, memory, and imaging. This Viewpoint summarizes the current state-of-knowledge regarding the macromolecular nitroxide radicals' redox mechanism, conductivity, chain conformation, controlled polymerization, network structure, conjugated forms, and applications. The nitroxide radical group is the focus because it is the most widely studied. Although most literature focuses upon applications, an emerging body of work is highlighting the fundamental physicochemical properties of macromolecular radicals. To this end, this Viewpoint recommends areas of opportunity in fundamental studies and best practices in reporting.

The free radical and controlled radical polymerization of sodium 4-vinylbenzenesulfonate using graphene oxide as a radical initiator was studied. This work demonstrates that graphene oxide can initiate radical polymerization in an aqueous solution without any additional initiator. Poly(sodium 4-vinylbenzenesulfonate) obtained via reversible addition–fragmentation chain transfer polymerization had a controlled molecular weight with a very narrow polydispersity ranging between 1.01 and 1.03. The reduction process of graphene oxide as well as the resulting composite material properties were analyzed in detail.

High grafting density polymer brushes are grown on an inimer coating bearing nitroxide-mediated polymerization (NMP) inimers and glycidyl methacrylate (GMA). The inimer coating is cross-linked on the substrate to provide an initiator layer with needed stability during long exposure to organic solvents at moderate to high temperatures. Surface-initiated nitroxide-mediated polymerization (SI-NMP) is conducted to grow polystyrene (PS) brushes on the coating with a sacrificial layer designed to cleave the brushes. The cleaved brushes have larger molecular weights than the corresponding free polymers. The grafting density of the brushes is as high as 1.12 chains/nm2 throughout the brush growth, which is among the densest PS brushes reported so far. Atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) depth profiling are used to reveal the surface morphology and kinetics of the growth.

A novel approach is presented whereby nitroxide-mediated radical polymerization (NMP) is conducted in an aqueous heterogeneous system at an initial polymerization rate an order of magnitude greater than the corresponding bulk system, accompanied by an improvement in the level of control over the molecular weight distribution. NMP of styrene mediated by

The synthesis of cyclic polystyrene (PSt) with an alkoxyamine functionality has been accomplished by intramolecular radical coupling in the presence of a nitroso radical trap. Linear α,ω-dibrominated polystyrene, produced by the atom transfer radical polymerization (ATRP) of styrene using a dibrominated initiator, was subjected to chain-end activation via the atom transfer radical coupling (ATRC) process under pseudodilute conditions in the presence of 2-methyl-2-nitrosopropane (MNP). This radical trap-assisted, intramolecular ATRC (RTA-ATRC) produced cyclic polymers in greater than 90% yields, possessing ⟨G⟩ values in the 0.8–0.9 range as determined by gel permeation chromatography (GPC). Thermal-induced opening of the cycles, made possible by the incorporated alkoxyamine, resulted in a return to the original apparent molecular weight, further supporting the formation of cyclic polymers in the RTA-ATRC reaction. Liquid chromatography–mass spectrometry (LC-MS) provided direct confirmation of the cyclic ar...

A new alkoxyamine based on a highly thermally stable nitroxide is used for the controlled polymerization of styrene and butyl acrylate at temperatures up to 200 °C. High monomer conversions are reached in a few minutes with a linear increase in polymer chain-length with conversion, a final dispersity (Đ) of ∼1.2, and successful chain-extension of the resulting material. The alkoxyamine concentration was altered to target various chain lengths, with autopolymerization dictating the polymerization rate of styrene regardless of alkoxyamine concentration. Controlled polymerization of methacrylate monomers and acrylic acid was successful with the addition of styrene. The new material opens the possibility to increase the range of specialty products made for applications in coatings, inks, overprint varnishes, and adhesives.

Anionic polymerization of 4-methacryloyloxy-TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidin-1-oxyl) was successfully carried out using methyl methacrylate-capped 1,1-diphenylhexyllithium (DPHLi/MMA), of which nucleophilicity is moderate enough to suppress the side reaction between the nitroxide radical of TEMPO moiety and the carbanion of DPHLi, to yield the radical polymer with well-controlled molecular weight, narrow polydispersity index (PDI1.10), high yield (95%), and almost 1.0 radicals per monomer unit.

Although both stable free organic radicals and biomass-derived hydrochars have emerged as appealing, green, multifunctional materials, their association has not been explored. In this study, strength is found to lie in their union, which primarily leads to stable redox-active free-radical-hydrochar composites that can generate unexpected opportunities for the development of advanced metal-free sustainable materials. The composites are obtained by a straightforward green one-pot hydrothermal procedure. The loading of stable free radicals of nitroxide type and their localization is engineered by the nature of the carbohydrate and the reaction status; vigorous reaction parameters promote faster nucleation and growth kinetics of the hydrochar products, leading to a covalent immobilization of redox species on the surface of the carbonaceous microspherical aggregates. The nitroxide free-radical-hydrochar materials demonstrate enhancements in terms of both electrocatalytic activity and capacitive features.

The mechanism of 1,2-substituted ethylene and 1,4-substituted butadiene oxidation with cyclic multiple chain termination by nitroxide radicals has been confirmed using a large set of nitroxides of piperidine, pyrroline, pyrrolidine and imidazoline series. This mechanism includes hydroperoxyl radicals as chain propagating agents and is realized both in non-polar and in polar media. The solvent effect on the rate constant of nitroxide and hydroperoxide radicals interaction is explained by the specific solvation of $${\text{HO}}_{{2}}^{{{ \bullet }}}$$ radicals. An additional effect in high dielectric constant media can be provided by the nonspecific solvation of nitroxide radicals. In low polar solvents the reactivity of > NO• is almost completely determined by > NO–H bond energy of hydroxylamine.

The use of redox-active organic compounds to make rechargeable batteries is a promising strategy for future energy storage especially from a resource and environmental sustainability point of view. While many organic structures have been identified as potential electroactive materials, their direct application in solid-state energy storage is limited. This is due to their high solubility in common organic electrolytes, resulting in poor long-term battery performance. In this work, we overcome this significant problem by synthesizing very low soluble nitroxide radicals with theoretical capacities of 111–131 mAh g−1, equal to or higher than most commonly used nitroxide radical polymers. These new structures consist of TEMPO (i.e. 2,2,6,6-tetramethylpiperidinyl-1-oxy) radicals and triazole ring linkages synthesized by the copper-catalyzed azide-alkyne cycloaddition (CuAAC) ‘click’ reaction. Analysis of electrode morphology and electrochemical performance at increasing mass loading of the nitroxide radicals demonstrate the importance of lower solubility, preventing the shuttle effect observed for common organic electrode materials. The electrodes with the content of active materials up to 80 wt% can still maintain a good interaction with the carbon and conductivity throughout the electrode and deliver a capacity greater than 60 mAh g−1 over 200 cycles.

X-band EPR spectroscopy and X-ray analysis (XRA) were used to study structure and dynamics of the intramolecular electron spin exchange in nitroxide biradical B1, in which radical rings are linked by two acethylene groups (–C≡C–) and two para-phenylene groups –(C6H4–) as well as of the corresponding radical R1. The existence of two (cys- and trans-) conformers with different values of the exchange integral of the biradical and conformational transitions between them have been revealed. The energetically most stable geometry of biradical B1 has been calculated using DFT method with its good agreement with the X-ray data.

Four biradical-Ln complexes with different transition metal ions, namely [LnM(hfac)5 (NITPh-PyPzbis)] (MII =MnII and LnIII =Gd 1, Dy 2; MII =NiII and LnIII =Tb 3, Dy 4), were prepared by the reaction of Ln(hfac)3 ⋅ 2H2 O, Mn(hfac)2 ⋅ 2H2 O or Ni(hfac)2 ⋅ 2H2 O with NITPh-PyPzbis biradical (hfac=hexafluoroacetylacetonate, NITPh-PyPzbis=5-(3-(2-pyridinyl)-1H-pyrazol-1-yl)-1,3-bis(1'-oxyl-3'-oxido- 4',4',5',5'-tetramethyl-4,5-hydro-1H-imidazol-2-yl)benzene). In complexes 1-4, the NITPh-PyPzbis biradical chelates one LnIII ion by means of its aminoxyl moieties and the transition metal ion is introduced through the two N donors from the pyridyl pyrazolyl moiety. Magnetic investigations indicate that complex 4 displays visible maxima in frequency/temperature-dependent χ'' signals with two-step relaxation processes, but complex 2 exhibits no slow magnetization relaxation. The comparison of structure parameters of both Dy complexes indicates that the symmetries of coordination spheres of two Dy ions are D2d for 2 and C2v for 4, which thus probably results in different magnetic relaxation behaviors. This work provides new insight for improving properties of Ln-biradical based SMMs.

Biobased farnesene (Far) was polymerized by nitroxide-mediated polymerization in miniemulsions using two different alkoxyamine initiators, the SG1-based and succinimidyl-modified BlocBuilder (NHS-BB) and Dispolreg 007 (D7). Stable emulsions were observed after 30 h of reaction at 90 °C, where NHS-BB-initiated systems resulted in smaller particles (∼300 nm) than using D7 (∼400 nm). Successful chain extension of the poly(Far) macroinitiators (24,500–39,700 g mol–1) with styrene were achieved using 15 wt % surfactant relative to monomer concentration. Compartmentalization effects were not observed in these emulsions as the polymerization rate was still much slower compared to the bulk, even though Z-averaged particle sizes were around 300–400 nm. Finally, all biobased diblock copolymers were synthesized by chain-extending poly(Far) macroinitiators with isobornyl methacrylate (iBOMA), where the D7 initiator showed more effective chain extension (less unreacted macroinitiator) than NHS-BB.

Hybrids, produced by hybridization of proteins, peptides, DNA, and other new biomolecules with polymers, often have unique functional properties. These properties, such as biocompatibility, stability and specificity, lead to various smart biomaterials. This review mainly introduces biomolecule-polymer hybrid materials by reversible deactivation radical polymerization (RDRP), emphasizing reverse addition-fragmentation chain transfer (RAFT) polymerization, and nitroxide mediated polymerization (NMP). It includes the methods of RDRP to improve the biocompatibility of biomedical materials and organisms by surface modification. The key to the current synthesis of biomolecule-polymer hybrids is to control polymerization. Besides, this review describes several different kinds of biomolecule-polymer hybrid materials and their applications in the biomedical field. These progresses provide ideas for the investigation of biodegradable and highly bioactive biomedical soft tissue materials. The research hotspots of nanotechnology in biomedical fields are controlled drug release materials and gene therapy carrier materials. Research showed that RDRP method could improve the therapeutic effect and reduce the dosage and side effects of the drug. Specifically, by means of RDRP, the original materials can be modified to develop intelligent polymer materials as membrane materials with selective permeability and surface modification.

It is well known that lipid carbon radicals (lipid radicals) are the origin of lipid peroxidation and are involved in various diseases such as cancer. Therefore, the in vivo detection of lipid radicals would be expected to lead to early diagnosis of these diseases. However, there are no methods for measuring lipid radicals in vivo. Nitroxides are known to be highly reactive with lipid radicals, but they tend to be reduced in vivo. Focusing on the excellent detection sensitivity of nuclear medical imaging, we have developed a radioiodinated nitroxide derivative with resistance to bioreduction for the in vivo detection of lipid radicals. The desired compound was obtained successfully and was highly stable against bioreduction while maintaining high reactivity toward lipid radicals. The I-125 labeling was efficacious with radiochemical yields of 84-87% and radiochemical purities of >99%. A cellular uptake assay showed that the radioiodinated compound was significantly taken up by cells under lipid radical-producing conditions compared to that in the absence of lipid radical production. A biodistribution study indicated that the radioiodinated compound accumulated more in organs where lipid peroxidation was promoted than the methoxyamine derivative, which lost reactivity to lipid radicals. These results indicated that the developed probe became trapped in cells or organs by reacting with lipid radicals. Thus, the radioiodinated nitroxide is a candidate probe for in vivo detection of lipid radicals.

Electrochemical processes in Li-O2 batteries benefit from the action of soluble electrocatalysts (redox mediators, RMs) that can facilitate charge or discharge reactions and minimize the blockage of the cathode with the insoluble discharge product Li2O2. In this work, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) analogues (RPTIOs) as new redox mediators for Li-O2 batteries have been investigated. Cyclic voltammetry, scanning electron microscopy, X-ray diffraction studies, and the galvanostatic cycling of the Li-O2 batteries showed that the RPTIOs could effectively catalyze the charge process while having a low impact on the discharge reaction. A direct connection was observed between the character of the substituent on the 2-position of the imidazoline ring, the oxidation redox potential of the RPTIO, and the value of the charge voltage of the battery with this RM, paving a path for further optimization.

International audience; Two mononuclear complexes [(Et3NH)[M(hfac)2L] (M = Ni, 1; Zn, 2) have been synthesized using a nitronyl-nitroxide radical substituted nitrophenol, that is 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl, HL, as a proligand. The crystal structures of 1 and 2 have been solved and indicate an octahedral coordination geometry of the metal ions. The magnetic behavior for 1 is characterized by a strong antiferromagnetic metal–radical interaction (J = −351 ± 1 cm−1; H = −JSNiSRad). This exchange interaction was rationalized by DFT calculations. The EPR spectra recorded in both solution and solid state at 120 K confirm the S = ½ ground state for 1.