Stable Nitroxyl Radicals Research Articles

Ab Initio Shape of Supramolecular Complexes of Cucurbit[8]uril in Solution Found from Small-Angle X-ray Scattering Data

Previous studies of the spatial structure of the guest–host complexes of macrocyclic cavitands cucurbiturils with a number of nitroxyl radicals by ESR, NMR, and crystallographic methods showed that, in aqueous solutions containing a number of nitroxyl radicals as guest molecules, ordered aggregates in the form of an equilateral triangle, with three guest–host monocomplexes located in its vertices, may arise. We performed experiments on small-angle X-ray scattering of aqueous solutions of guest–host cucurbit[8]uril complexes with a stable nitroxyl radical (protonated tempoamine) and, based on the experimental results, carried out ab initio modeling of the shape of aggregates of complexes in the natural state in solution. The search for models of the shape of aggregates was performed either using no additional information about their structure or assuming the presence of a threefold axis. ESR is applied as an independent method for studying the aggregation of complexes in solution. It is shown that the shape of the particles constituting complexes at high cavitand and guest concentrations in an aqueous solution is close in its parameters to an equilateral triangle, which is in agreement with the known crystallographic and ESR data.

A NEW QUANTITATIVE METHOD OF EXPRESS ANALYSIS OF NATURAL RUBBER DIRECTLY IN THE ROOT OF THE RUBBER PLANT BY THE SPIN PROBE EPR METHOD

In this work, the phenomenon of selective sorption of a stable nitroxyl radical TEMPO on rubber particles in the powder of dried and dispersed root of kok-sagyz was discovered. This feature of the rubber-bearing root material contributed to the development of a new, highly sensitive method of quantitative analysis of rubber by the integral intensity of the EPR TEMPO signal. The main advantages of the proposed method are the speed and the ability to determine the content of rubber directly in the roots of the plant in microquantities (5–30 mg).

Mutual Activation of Two Radical Trapping Agents: Unusual "Win-Win Synergy" of Resveratrol and TEMPO during Scavenging of dpph• Radical in Methanol.

The reaction of the 2,2'-diphenyl-1-picrylhydrazyl radical (dpph•) with resveratrol in methanol (kMeOH = 192 M-1 s-1) is greatly accelerated in the presence of stable nitroxyl radical TEMPO• (kmixMeOH = 1.4 × 103 M-1 s-1). This synergistic effect is surprising because TEMPO• alone reacts with dpph• relatively slowly (kS = 31 M-1 s-1 in methanol and 0.03 M-1 s-1 in nonpolar ethyl acetate). We propose a putative mechanism in which a mutual activation occurs within the acid-base pair TEMPO•/RSV to the resveratrol (RSV) anion and TEMPOH•+ radical cation, both being extremely fast scavengers of the dpph• radical. The fast initial reaction is followed by a much slower but continuous decay of dpph• because a nitroxyl radical is recovered from the TEMPOnium cation, which is reduced directly by RSV/RSV- to TEMPO• or recovered indirectly via a reaction with methanol, producing TEMPOH subsequently oxidized by dpph• to TEMPO•.

Heterogeneous Catalysis for Oxidation of Alcohol via 1‐Methyl‐2‐azaadamanane N‐oxyl Immobilized on Magnetic Polystyrene Nanosphere

AbstractHeterogeneous selective oxidation of alcohol to carbonyl compounds with stable organic nitroxyl radicals is highly attractive yet grand challenging. Described herein is a highly promising heterogeneous strategy for this reaction in which a catalytic amount of 1‐methyl‐2‐azaadamanane N‐oxyl immobilized on magnetic polystyrene nanosphere (1‐Me‐AZADO/MPNs) was used and a series of carbonyl compounds were obtained from various alcohols in 73–99 % isolated yields and high selectivity (>99 %) under Anelli conditions, thus offering a greener and more convenient methods in the synthesis of carbonyl compounds. The attractive features of convenient magnetic separation (within seconds), good recyclability (up to 20 runs) and fast reaction rates (5–20 min) were very efficient to improve the utility of azaadamantane‐type‐nitroxyl radicals in the oxygenation.

Влияние озона на структуру биоразлагаемых матриц на основе смесей поли(3-гидроксибутирата), полилактида и хитозана

Changes in fibrous and film materials based on mixtures of biodegradable polyesters polyhydroxybutyrate, polylactide, and chitosan polysaccharide during ozonolysis were studied by the structural-dynamic EPR method using a stable nitroxyl radical—the TEMPO probe. Fibers and films were obtained from solutions in chloroform, respectively, by electrospinning and casting onto glass. It is shown that the lower packing density in the amorphous regions of mixed samples determines the increased rate of their oxidation by ozone compared to homopolymers. A two-stage kinetic mechanism of ozonolysis has been demonstrated, including the formation of side groups and subsequent degradation of the polymer chain. It has been found that the activation energy of probe rotation depends on the amount of polymer in the mixture, while the activation barrier is minimal for polyester mixtures in the same concentration range where the ozonolysis constants are maximum. It has been shown that the presence of chitosan in ternary compositions leads to an increase in the degree and rate of ozonolysis.

LONG-TERM RADIATION-INDUCED EFFECTS ON SOLID STATE CHITOSAN

Treatment of chitosan with ionising radiation is one of the methods by which it is modified for various applications. However, in the case of chitosan irradiated in the solid state, the radicals formed during irradiation can be stabilised in its crystalline phase and subsequently cause post-irradiation changes. It has been observed that further degradation of the polymer occurs during storage of the irradiated polymer, resulting in an increase in oxidation products and a decrease in deacetylation degree. This effect results from the transformation of radicals leading to the formation of stable nitroxyl radicals, a process observed years after irradiation.

A Case Study on the Desired Selectivity in Solid-State Mechano- and Slow-Chemistry, Melt, and Solution Methodologies.

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.

Achieving Maximal Enhancement of Electron Spin Polarization in Stable Nitroxyl Radicals at Room Temperature.

Enhancing the polarization of spin levels at room temperature is one of the active research areas in magnetic resonance. Generation of electron spin hyperpolarization involves a complex interplay of electronic and spin processes. In this work, the optimization of crucial electron spin polarization (ESP) generating parameters and synthesis of a radical-chromophore adduct are described. The ESP of the synthesized adduct is about 550 times the equilibrium polarization at room temperature, which is possibly the maximal value for a chromophore-nitroxyl system. The present work highlights the crucial role of the photophysical quenching process toward the generation of a large ESP. Additionally, a chromophore-diradical adduct is synthesized, and the effects of the additional radical in the ESP generation process are discussed. Enhanced photochemical stability is demonstrated for the diradical adducts, thereby suggesting a potential route toward the generation of photostable radical-chromophore adducts for future studies. The large ESP in these molecules should enable a wide range of applications, such as in DNP, spintronics, and magnetometers.

Lanthanide Complexes with a Tripodal Nitroxyl Radical Showing Strong Magnetic Coupling.

A series of isomorphous mononuclear complexes of Ln(III) ions comprising one stable tripodal oxazolidine nitroxyl radical were obtained in acetonitrile media starting from nitrates. The compounds, [LnRad(NO3)3] (Ln = Gd, Tb, Dy, Tm, Y; Rad = 4,4-dimethyl-2,2-bis(pyridin-2-yl)-1,3-oxazolidine-3-oxyl), have a molecular structure. Their coordination polyhedron, LnO7N2, can be described as a tricapped trigonal prism with symmetry not far from D3h. The extracted value of 23 cm-1 for the antiferromagnetic coupling of Gd-Rad established from the DC magnetic and EPR data is a record strength for the complexes of 4f elements with nitroxyl radicals. The terbium derivative displays frequency-dependent out-of-phase signals in zero field, indicating single-molecule magnetic behavior. With an applied field of 0.1 T, an effective barrier of 57 cm-1 is found.

Probing the efficiency of thermal and photochemical bond homolysis in functionalized nanostructured SBA-15 silicas

Abstract The formation of radical species in solution can be triggered through thermal or photochemical activation of a suitable precursor. This EPR study aimed to establish if these two activation modes were as effective in mesoporous silicas as in solution. First, a calibration system was devised and validated to reliably quantify the radical formation. Alkoxyamines were selected to generate stable nitroxyl radicals upon heating or irradiation. Thanks to direct synthesis by the sol-gel process, these precursors were selectively located on the pore surface or in the framework of mesoporous silicas. The thermal or photo-chemical activation of the functionalized materials showed that nitroxides were formed in yields comparable to those observed in solution. No significant differences were observed with the implementation of these activation modes between the solution and the mesoporous silicas. Moreover, the thermal experiments enabled to measure the C–O bond dissociation constants of alkoxyamines covalently anchored to a nanostructured silica, their values were in the same order of magnitude than those determined in solution.

Structural analysis of a glucoglucuronan derived from laminarin and the mechanisms of its anti-lung cancer activity

Laminarin (LA), a storage glucan, was purified from the brown alga Sargassum thunbergii. After specific oxidation using the stable nitroxyl radical, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), together with NaBr and NaClO, glucoglucuronan (LAO) was obtained. Compositional analysis of LAO showed a molar ratio of glucuronic acid (GlcA) to glucose (Glc) of 12.7: 1. Nuclear magnetic resonance (NMR) and mass spectroscopy (MS) showed LAO to have a backbone of (1 → 3)-linked β-D-GlcpA interspersed with (1 → 3, 1 → 6)-linked β-D-Glcp, that was terminated with β-D-GlcpA. LAO inhibited human lung cancer A549 cell proliferation in vitro. IC50 values at 12 h and 24 h were 2.70 mg/mL and 2.85 mg/mL, respectively. Western blotting showed that TSC2 was up-regulated at an LAO concentration of 3.80 mg/mL. FAK, PI3K, P-AKT and mTOR were down-regulated, indicating LAO inhibited cancer cell proliferation through the FAK/PI3K/AKT/mTOR pathway. Surface plasmon resonance (SPR) studies revealed that LAO showed an IC50 of 0.07 mg/mL inhibiting the binding of heparin to fibroblast growth factor 1 (FGF1) LAO inhibition of heparin binding to FGF2 fluctuated between 15% and 28%, suggesting that LAO inhibits A549 cell proliferation by selectively interacting with FGF1.

Possible artefacts of antioxidant assays performed in the presence of nitroxides and nitroxide-containing nanoparticles

Nitroxides and nitroxide-containing nanoparticles (RNP) are excellent antioxidants. However, they have relatively high reduction potentials, which make them behave like oxidants or show little activity in some antioxidant assays. We found that stable nitroxyl radicals (TEMPO and 4-amino-TEMPO) has low reactivity in the test of scavenging of 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical (ABTS•). As a result, supplementation of blood plasma with nitroxides may decrease its total antioxidant capacity assayed with ABTS•. Nitroxides oxidize Fe2+ and in this way interfere with the ferric-Xylenol Orange assay of peroxides. Nitroxides as well as RNP directly oxidize glutathione and fluorogenic probes used for estimation of reactive oxygen species (ROS) (dihydro-2′7′-dichlorofluorescein diacetate, dihydroethidine and dihydrorhodamine 123) and thus produce artefacts in assays of glutathione and ROS in cell-free and cellular systems. These results point to the necessity of careful interpretation of antioxidant assays concerning nitroxides and RNP or performed in their presence.

Initiated and Inhibited Oxidation of 1,1-Dichloro-2-Methyl-2-Vinylcyclopropane

Initiated and inhibited oxidation of 2-methyl-2-vinyl-gem-dichlorocyclopropane has been studied. It has been found that in the oxidation process, chain propagation occurs via the addition of a polyperoxy radical to the double bond. The studied monomer is close to methacrylic acid esters in activity. The inhibiting effect of phenol and amine antioxidants and stable nitroxyl radicals on the radical chain oxidation of 2-methyl-2-vinyl-gem-dichlorocyclopropane has been examined, and amines and nitroxyls have been shown to repeatedly terminate chains due to the regeneration of the inhibitor.

Radical Intermediates in Reactions of Mixed Phosphonium–Iodonium Ylides

The active intermediates generated in the photolysis of phosphonium–iodonium ylides and their reaction with acetylenes have been studied with electron and nuclear magnetic resonance spectroscopy. The radical mechanism of the ylides decomposition and of the interaction with acetylenes has been established using a stable nitroxyl radical. The radical products of these reactions have been monitored for the first time by EPR, and their spectroscopic parameters were determined. The chemical structure of the active intermediates of the reactions under study has been proposed.

Nitrogen Dioxide Catalyzed Aerobic Oxidative Cleavage of C(OH)-C Bonds of Secondary Alcohols to Produce Acids.

Stable organic nitroxyl radicals are an important class of catalysts for oxidation reactions, but their wide applications are hindered by their steric hinderance, high cost, complex operation, and separation procedures. Herein, NO2 in DMSO is shown to effectively catalyze the aerobic oxidative cleavage of C(OH)-C bonds to form a carboxylic group, and NO2 was generated in situ by decomposition of nitrates. A diverse range of secondary alcohols were selectively converted into acids in excellent yields in this transition-metal-free system without any additives. Preliminary results also indicate its applicability to depolymerize recalcitrant macromolecular lignin. Detail studies revealed that NO2 from nitrates promoted the reaction, and NO2 served as hydrogen acceptor and radical initiator for the tandem oxidative reaction.

Toward Achieving the Theoretical Limit of Electron Spin Polarization in Covalently Linked Radical-Chromophore Dyads.

Electron spin systems with non-Boltzmann spin distributions are commonly observed in photophysical and photochemical processes involving free radicals. Understanding the origin of electron spin polarization (ESP) reveals detailed insight into the spin-dependent interactions occurring in these processes. The ability to transfer ESP to the nuclear spins of the solvent to produce large nuclear polarization is itself an active area of research in the field called dynamic nuclear polarization (DNP). Harnessing ESP in such fields demands a large magnitude of ESP and importantly on free radicals that are stable. In this work, we explored various factors that could play a prominent role in generation of ESP on the stable nitroxyl radical. By exploiting the dependence of ESP on the zero-field splitting parameter DT of the chromophore triplets and a careful choice of the chromophores for efficient quenching of their excited states by a free radical, we present here our strategies for designing covalently linked chromophore-free radical dyads, which could generate high magnitudes of ESP. Syntheses and EPR studies on a series of such dyads to demonstrate successful realization of our strategy are reported here. Our work reveals that, along with the DT value and the triplet quenching efficiency, the relative orientational dynamics of the radical and chromophore moiety and an efficient intersystem crossing of the chromophore primarily govern the ESP of the chromophore-radical dyads. One such molecule, an anthraquinone moiety linked to a TEMPO free radical that optimally satisfies the above criteria, produces a very large value of ESP-about 300 times its Boltzmann value-reaching almost half of the theoretical maximum of the radical-triplet pair mechanism of ESP. Coupled with its excellent photostability in benzene and the use of ambient conditions, this molecule should prove to be highly desirable in photoinduced DNP studies and other applications such as highly sensitive magnetometers, which require generation of large nuclear spin polarization in the solvent by transferring the electron spin polarization.

Real-Time Insight into the Doping Mechanism of Redox-Active Organic Radical Polymers

In recent years, organic radical polymers have received great attention as active materials for fast-charging battery electrodes. Organic radical polymers are electrochemically active owing to the reversible reduction-oxidation (redox) reaction of pendant radical groups and offer a vast synthetic landscape for customization. Interest in these polymers as battery electrodes has grown due to its high theoretical capacities, fast electron transfer kinetics, and long cyclability. One commonly studied stable nitroxide radical polymer is poly(2,2,6,6-tetramethylpiperidinyloxy methacrylate) (PTMA). This electroactive material consists of stable nitroxyl radical groups attached to a polymethylacrylate backbone. Upon oxidation or charging, the neutral nitroxide radical transfers an electron to the current collector, resulting in an oxoammonium cation. Simultaneously, anions dope the polymer cathode to maintain charge neutrality. Upon reduction or discharging, the polymer is de-doped and the neutral nitroxide radical is retrieved. Electronic charge transfer within the organic radical polymer occurs by an electron hopping mechanism with Brownian motion of the redox centers. Although there is much more understood about electron transfer in organic radical polymers, there is significantly less understood regarding mass transfer and the doping mechanism, which is equally important for understanding the overall redox mechanism. Here, we specifically examine ion transport in PTMA cathodes for nonaqueous batteries. Using in situ electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D), we quantitatively observe the ion transport (or doping) process in organic radical polymers during the redox process for the first time. EQCM-D monitors changes in frequency and dissipation of a PTMA-coated quartz crystal during cyclic voltammetry. The change of mass and shear viscosity can be further obtained from viscoelastic modeling of the raw data, leading to a quantitative view of mass transport associated with the doping process. This work is reported in Wang, S., Li, F., Easley, A.D., & Lutkenhaus, J.L., Nature Materials 18 (1), 69-75 (2019). Here, we quantify the real-time mass transfer of anions and solvent during the reduction and oxidation of PTMA, which allows for the first-ever separation of lithium expulsion and anion uptake in an organic radical polymer. This is accomplished using in situ electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D) during cyclic voltammetry, a method that yields the instantaneous electrode mass change and shear modulus via viscoelastic modeling. We present an analysis method for PTMA by which the mass exchanged per electron transferred is quantified, and, in some cases, the number of solvent molecules transferred can also be calculated. Our results show that two doing modes dominate in oxidation: doping by lithium-ion expulsion and doping by anion uptake. The effect of dopant anion type (i.e. CF3SO3 -, ClO4 -, and BF4 -), the degree of solvent participation, and the effect on charge storage behavior with mass transport is correlated to polymer-dopant and dopant-solvent interactions. Understanding the detailed mass and charge transport process is a leap forward in describing the redox reaction doping mechanism in organic radical polymers and adds a new facet of discussion in the nature of electron transport, as the two are intimately coupled. In turn, this may impact the future design of organic radical polymers for any application in which the polymer is in contact with electrolyte (organic batteries, electrochromics, sensors).

Complex macromolecular structures from stable radical containing block copolymers

ABSTRACTA novel synthetic strategy for the synthesis of graft copolymers is reported. Block copolymers containing segments with stable nitroxyl radicals side groups were first prepared by anionic polymerization, which were then used as a precursor for the subsequent nitroxide‐mediated radical polymerization (NMRP) of styrene. This way, block–graft copolymers with polystyrene side chains grafted from one of the blocks were successfully synthesized in a controlled manner. In addition, block–graft copolymers with grafted polystyrene chains and a poly(tert‐butyl methacrylate) block were subjected to hydrolysis to yield the corresponding amphiphilic polymers. The structures and the molecular weight characteristics of the polymers were characterized by spectral and chromatographic analyses. The surface morphology of thus obtained polymers was also investigated by microscopic techniques. © 2019 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 62–69

Novel highly conductive cathode material based on stable-radical organic framework and polymerized nickel complex for electrochemical energy storage devices

Redox polymers bearing stable nitroxyl radical groups, such as poly-TEMPO-methacrylate (PTMA), are attractive candidates for application in power sources of novel kind, which combine the high power output of supercapacitors and high energy of rechargeable batteries. An important advantage of PTMA is the availability and low cost of the starting materials combined with high charging/discharging voltage, fast electron transfer kinetics and good mechanical properties of the polymer. However, low electron conductivity and high solubility in common organic electrolytes hamper the broad application of TEMPO-based compounds as cathode materials. In the present work, we report a simple strategy to overcome these limitations by the use of a practical and polymer-rich electrode based on redox-conducting polymer blends of polymerized nickel complexes with salen-type Schiff bases and PTMA. Electrochemical properties of the material are tested both in thin film systems and in asymmetric supercapacitor prototypes with aqueous electrolyte, which demonstrate high specific capacity (83 mAh g−1 at 1C, 53 mAh g−1 at 5C and 47 mAh g−1 at 10C), high rate capability as well as cycling stability (55% capacity retention after 1000 cycles).

Enantioselective Synthesis of Pyrroloindolines via Noncovalent Stabilization of Indole Radical Cations and Applications to the Synthesis of Alkaloid Natural Products.

While interest in the synthetic chemistry of radical cations continues to grow, controlling enantioselectivity in the reactions of these intermediates remains a challenge. Based on recent insights into the oxidation of tryptophan in enzymatic systems, we report a photocatalytic method for the generation of indole radical cations as hydrogen-bonded adducts with chiral phosphate anions. These noncovalent open-shell complexes can be intercepted by the stable nitroxyl radical TEMPO· to form alkoxyamine-substituted pyrroloindolines with high levels of enantioselectivity. Further elaboration of these optically enriched adducts can be achieved via a catalytic single-electron oxidation/mesolytic cleavage sequence to furnish transient carbocation intermediates that may be intercepted by a wide range of nucleophiles. Taken together, this two-step sequence provides a simple catalytic method to access a wide range of substituted pyrroloindolines in enantioenriched form via a standard experimental protocol from a common synthetic intermediate. The design, development, mechanistic study, and scope of this process are presented, as are applications of this method to the synthesis of several dimeric pyrroloindoline natural products.