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Gossypol and its derivatives arouse interest due to their broad spectrum of biological activities. Despite its wide potential application, there is no reported example of gossypol derivatives bearing stable radical functional groups. The first gossypol nitroxide hybrid compound was prepared here via formation of a Schiff base. By this approach, synthesis of a gossypol nitroxide conjugate was performed by condensation of gossypol with a 4-amino-TEMPO (4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl) free radical, which afforded the target product in high yield. Its structure was proven by a combination of NMR and EPR spectroscopy, infrared spectroscopy, mass spectrometry, and high-resolution mass spectrometry. In addition, the structure of the gossypol nitroxide was determined by single-crystal X-ray diffraction measurements. In crystals, the paramagnetic Schiff base exists in an enamine–enamine tautomeric form. The tautomer is strongly stabilized by the intra- and intermolecular hydrogen bonds promoted by the resonance of π-electrons in the aromatic system. NMR analyses of the gossypol derivative proved that in solutions, the enamine–enamine tautomeric form prevailed. The gossypol nitroxide at micromolar concentrations suppressed the growth of tumor cells; however, compared to gossypol, the cytotoxicity of the obtained conjugate was substantially lower. [ABSTRACT FROM AUTHOR]

Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (Fe3O4 NPs) using dendrimer polymers, yielding Fe3O4-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, Fe3O4 NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in Fe3O4-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that Fe3O4-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects. [ABSTRACT FROM AUTHOR]

Oxidative stress is a major source of ROS-mediated damage to macromolecules, tissues, and the whole body. It is an important marker in the severe picture of pathological conditions. The discovery of free radicals in biological systems gives a "start" to studying various pathological processes related to the development and progression of many diseases. From this moment on, the enrichment of knowledge about the participation of free radicals and free-radical processes in the pathogenesis of cardiovascular, neurodegenerative, and endocrine diseases, inflammatory conditions, and infections, including COVID-19, is increasing exponentially. Excessive inflammatory responses and abnormal reactive oxygen species (ROS) levels may disrupt mitochondrial dynamics, increasing the risk of cell damage. In addition, low serum albumin levels and changes in the normal physiological balance between reduced and oxidized albumin can be a serious prerequisite for impaired antioxidant capacity of the body, worsening the condition in patients. This review presents the interrelationship between oxidative stress, inflammation, and low albumin levels, which are hallmarks of COVID-19. [ABSTRACT FROM AUTHOR]

Gossypol and its derivatives arouse interest due to their broad spectrum of biological activities. Despite its wide potential application, there is no reported example of gossypol derivatives bearing stable radical functional groups. The first gossypol nitroxide hybrid compound was prepared here via formation of a Schiff base. By this approach, synthesis of a gossypol nitroxide conjugate was performed by condensation of gossypol with a 4-amino-TEMPO (4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl) free radical, which afforded the target product in high yield. Its structure was proven by a combination of NMR and EPR spectroscopy, infrared spectroscopy, mass spectrometry, and high-resolution mass spectrometry. In addition, the structure of the gossypol nitroxide was determined by single-crystal X-ray diffraction measurements. In crystals, the paramagnetic Schiff base exists in an enamine–enamine tautomeric form. The tautomer is strongly stabilized by the intra- and intermolecular hydrogen bonds promoted by the resonance of π-electrons in the aromatic system. NMR analyses of the gossypol derivative proved that in solutions, the enamine–enamine tautomeric form prevailed. The gossypol nitroxide at micromolar concentrations suppressed the growth of tumor cells; however, compared to gossypol, the cytotoxicity of the obtained conjugate was substantially lower.

Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (Fe3O4 NPs) using dendrimer polymers, yielding Fe3O4-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, Fe3O4 NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in Fe3O4-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that Fe3O4-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects.

Gold nanoparticles (AuNPs) possess remarkable optical properties and electrical conductivity, making them highly relevant in various fields such as medical diagnoses, biological imaging, and electronic sensors. However, the existing methods for modulating the optical properties of AuNPs are often under limitations such as a high cost, the complexity of detection, a narrow range of application settings, and irreversibility. In this study, we propose a novel approach to address these challenges by constructing a reversible electrochemical switch. The switch (ITO-OMAD) involves covalently linking nitroxide radicals and AuNPs (AuNPs-NO•), followed by tethering this nanocomposite to a siloxane-derived indium tin oxide (ITO) electrode. By simply electrochemically oxidizing/reducing the nitroxide units, one is able to reversibly modulate the optical properties of AuNPs at will. The surface morphology and structure of the as-prepared ITO-OMAD electrode were characterized through scanning electron microscopy (SEM) and cyclic voltammetry (CV). SEM imaging confirmed the successful anchoring of AuNPs on the ITO electrode. Electrochemical tests performed in the three-electrode system demonstrated that the local surface plasmon resonance (LSPR) of AuNPs can be reversibly regulated by alternatively imposing ± 0.5V (vs. Ag/AgCl) to the modified electrode. The development of this electrochemical switch presents a novel approach to effectively control the optical properties of AuNPs. The further exploration and utilization of this reversible electrochemical switch could significantly enhance the versatility and practicality of AuNPs in numerous applications. [ABSTRACT FROM AUTHOR]

The interaction of mono- and tetranuclear hexafluoroacetylacetonates [M4(hfac)4(OMe)4(MeOH)4] (where М = Co, Ni) and [Cu4(hfac)4(OMe)4] with spin-labeled nitrophenols - nitronyl nitroxide 2-(2-hydroxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (HL1) or with corresponding iminonitroxide (HL2) - is found to lead to the formation of solvates of binuclear complexes: [Co2(hfac)2(L2)2(H2O)2], [Ni2(hfac)2(L1)2(H2O)2], [Ni2(hfac)2(L2)2(H2O)], [Cu2(hfac)2(L1)2]. The magnetochemical analysis reveals that exchange interactions between metal ions and coordinated nitronyl nitroxides are strongly feroomagnetic and result in the compensation of spins. Imino nitroxide L2 substitution for nitronyl nitroxide L1 changes the character of exchange interactions in the heterospin molecule to the ferromagnetic one. [ABSTRACT FROM AUTHOR]

A method for the controlled filling of pores in metal–organic frameworks (MOFs) with ionic liquids (ILs) has been proposed, which can be applied for selective gas sorption in MOFs. Using an example of MOF ZIF-8 and IL [BMIm]+[BF4]−, composites with different IL content have been prepared with monitoring by electron paramagnetic resonance (EPR) of nitroxide spin probes. The effect of IL on the sorption of nitrogen(II) oxide into these composites has been studied using inversion gas chromatography. [ABSTRACT FROM AUTHOR]

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.

[Display omitted] • Spin-labeled pH-responsive diblock copolymers could be potentially used for controlled drug delivery applications. • Microfluidic technique offers a powerful and versatile platform for the precise synthesis of nanoparticles. • Electron paramagnetic resonance is a valuable technique for the molecular-level analysis of colloidal polymer systems. This research emphasizes the crucial role of electron paramagnetic resonance (EPR) spectroscopy in nanoparticle analysis, showcasing its distinctive ability to probe molecular-level details. We demonstrate the synthesis and self-assembly of a new class of pH-responsive amphiphilic diblock copolymers, specifically poly[ N -(2-hydroxypropyl)-methacrylamide]- block -poly[2-(diisopropylamino)ethyl methacrylate] (PHPMA- b -PDPA), incorporating 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radicals covalently bound to the hydrophilic PHPMA segment. The copolymer synthesis involved a three-step process, combining reversible addition − fragmentation chain transfer (RAFT) polymerization with carbodiimide (DCC) chemistry. TEMPO radical-containing nanoparticles (RNPs) were created using microfluidic (MF) nanoprecipitation, a technique essential for generating uniform nanoparticles with predictable biodistribution and cellular uptake. Adjusting MF protocol parameters allowed fine-tuning of RNP sizes. EPR spectroscopy confirmed the formation of core–shell RNPs, with features aligning closely with those obtained from scattering techniques like dynamic light scattering (DLS), static light scattering (SLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo-TEM). EPR spectroscopy emerges as a potent tool for molecular-level analysis of colloidal polymer systems. This study highlights the EPR-spin label method's efficacy in probing the internal structural features and dynamics of core–shell nanoparticles, especially their response to pH-triggered disassembly. The findings open new avenues for the use of pH-responsive TEMPO-labeled diblock copolymers in controlled drug delivery applications. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) possess remarkable optical properties and electrical conductivity, making them highly relevant in various fields such as medical diagnoses, biological imaging, and electronic sensors. However, the existing methods for modulating the optical properties of AuNPs are often under limitations such as a high cost, the complexity of detection, a narrow range of application settings, and irreversibility. In this study, we propose a novel approach to address these challenges by constructing a reversible electrochemical switch. The switch (ITO-OMAD) involves covalently linking nitroxide radicals and AuNPs (AuNPs-NO•), followed by tethering this nanocomposite to a siloxane-derived indium tin oxide (ITO) electrode. By simply electrochemically oxidizing/reducing the nitroxide units, one is able to reversibly modulate the optical properties of AuNPs at will. The surface morphology and structure of the as-prepared ITO-OMAD electrode were characterized through scanning electron microscopy (SEM) and cyclic voltammetry (CV). SEM imaging confirmed the successful anchoring of AuNPs on the ITO electrode. Electrochemical tests performed in the three-electrode system demonstrated that the local surface plasmon resonance (LSPR) of AuNPs can be reversibly regulated by alternatively imposing ± 0.5V (vs. Ag/AgCl) to the modified electrode. The development of this electrochemical switch presents a novel approach to effectively control the optical properties of AuNPs. The further exploration and utilization of this reversible electrochemical switch could significantly enhance the versatility and practicality of AuNPs in numerous applications.

The assessment of unregulated level of enzyme activity is a crucial parameter for early diagnoses in a wide range of pathologies. In this study, we propose the use of electron paramagnetic resonance (EPR) as an easy method to probe carboxylesterase (CE) enzymatic activity in vitro. For this application, were synthesized two amphiphilic, nitroxide containing esters, namely Tempo‐C12 (T‐C12) and Tempo‐2‐C12 (T‐2‐C12). They exhibit low solubility in water and form stable micelles in which the radicals are EPR almost silent, but the hydrolysis of the ester bond yields narrows and intense EPR signals. The intensity of the EPR signals is proportional to the enzymatic activity. CEs1, CEs2 and esterase from porcine liver (PLE) were investigated. The obtained results show that T‐C12 and T‐2‐C12‐containing systems display a much higher selectivity toward the CEs2, with a Limit of Detection of the same order of those ones obtained with optical methods. [ABSTRACT FROM AUTHOR]

Significance: Ischemia–reperfusion (IR) injury is a major component of severe damage in vascular occlusion during stroke, myocardial infarction, surgery, and organ transplantation, and is exacerbated by the excessive generation of reactive oxygen species (ROS), which occurs particularly during reperfusion. With the aging of the population, IR injury is becoming a serious problem in various organs, such as the kidney, brain, and heart, as well as in the mesenteric capillaries. Recent Advances: To prevent reperfusion injuries, natural and synthetic low-molecular-weight (LMW) antioxidants have been well studied. Critical Issues: However, these LMW antioxidants have various problems, including adverse effects due to excessive cellular uptake and their rapid clearance by the kidney, and cannot fully exert their potent antioxidant capacity in vivo. Future Directions: To overcome these problems, we designed and developed redox polymers with antioxidants covalently conjugated with them. These polymers self-assemble into nanoparticles in aqueous media, referred to as redox nanoparticles (RNPs). RNPs suppress their uptake into normal cells, accumulate at inflammation sites, and effectively scavenge ROS in damaged tissues. We had developed two types of RNPs: RNPN, which disintegrates in response to acidic pH; and RNPO, which does not collapse, regardless of the environmental pH. Utilizing the pH-sensitive and -insensitive characteristics of RNPN and RNPO, respectively, RNPs were found to exhibit remarkable therapeutic effects on various oxidative stress disorders, including IR injuries. Thus, RNPs are promising nanomedicines for use as next-generation antioxidants. This review summarizes the therapeutic impacts of RNPs in the treatment of kidney, cerebral, myocardial, and intestinal IR injuries. Antioxid. Redox Signal. 36, 70–80. [ABSTRACT FROM AUTHOR]

The structures of hexafluoroacetylacetonate complexes of Cu(II)–Cu(hfac)2– with nitroxide radicals LR1/R2, where R1 and R2 are alkyl substituents in the 1,3-pyrazole moiety are studied by X-ray crystallography. It is found that solid phases of all [Cu(hfac)2LR1/R2] are formed by polymeric chains whose common structural motif is a ditopic bridging coordination of paramagnetic ligands in the head-to-head fashion. The study of the temperature structure dynamics and the related change in the temperature dependence of the effective magnetic moment of the complex shows that changes in both R1 and R2 can substantially affect not only the possibility of the appearance of magnetic anomalies on the temperature curve of the effective magnetic moment but also its shape. [ABSTRACT FROM AUTHOR]

A 12-nuclear heterospin complex of Cu(II) hexafluoroacetylacetonate with dialkylpyrazolyl-substituted nitroxide [Cu2(hfac)4LBu/Et]6 is found, which has a previously unknown molecular structure for heterospin compounds where six {Cu(hfac)2(LBu/Et)} moieties form a 42-membered metallacycle. The ditopic function of connecting organic bridges between Cu atoms is performed by paramagnetic LBu/Et ligands forming a head-to-tail motif inside the metallacycle due to the coordination of the nitrogen atoms of the pyrazole ring (NPz) and one of the oxygen atoms (ONO) of the nitronyl nitroxide moiety. Each LBu/Et completes its structural function to tritopic due to the coordination of the second ONO atom by yet another Cu(hfac)2 moiety. Butyl substituents of the pyrazole moiety tightly fill the space inside the metallacycle, preventing the inclusion of any solvent molecules. Ethyl substituents of the pyrazole rings, methyl groups of the imidazoline moiety, and trifluoromethyl groups of hexafluoroacetylacetonate anions directed into the intermolecular space push the metallacycles apart. As a result, the neighboring metallacycles are magnetically isolated from each other, and the character of the temperature dependence of the effective magnetic moment is determined by strong antiferromagnetic interactions between nitroxides and terminal Cu(hfac)2 moieties inside 12-nuclear molecules. Because of these interactions, below 160 K only spins of intracyclic Cu(II) ions, weakly interacting with each other, contribute to the magnetic susceptibility. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Doubly charged peroxylamine disulfonate (Frémy's salt) resides in the polar nanodomains of room-temperature ionic liquids. • Neutral di- tert -butyl nitroxide (DTBN) resides in the nonpolar nanodomains of room-temperature ionic liquids. • Rotational anisotropy of Frémy's salt increases with increasing cation alkyl chain length. • The activation energy of the rotation of Frémy's salt and di- tert -butyl nitroxide is the same as that of the viscous flow. • Long-range collective motion governs the activation energy of Frémy's salt and di- tert -butyl nitroxide rotation. We have studied the rotational diffusion of two prolate nitroxide probes, the doubly negatively charged peroxylamine disulfonate (Frémy's salt − FS) and neutral di- tert -butyl nitroxide (DTBN), in a series of 1-alkyl-3-methylimidazolium tetrafluoroborate room-temperature ionic liquids (RTILs) having alkyl chain lengths from two to eight carbons using electron paramagnetic resonance (EPR) spectroscopy. Though the size and shape of the probes are reasonably similar, they behave differently due to the charge difference. The rotation of FS is anisotropic, and the rotational anisotropy increases with the alkyl chain length of the cation, while the rotation of DTBN is isotropic. The hyperfine coupling constant of DTBN decreases as a function of the alkyl chain length and is proportional to the relative permittivity of ionic liquids. On the other hand, the hyperfine coupling constant of FS increases with increasing chain length. These behaviors indicate the location of each probe in RTILs. FS is likely located in the polar region near the network of charged imidazolium ions. DTBN molecules are predominately distributed in the nonpolar domains. [ABSTRACT FROM AUTHOR]

Introduction. Polymeric materials (PM) are increasingly used in various industries and agriculture. Under the action of UV light, PM are destroyed. UV stabilizers are used to protect PM from photodegradation. Their action is based on the absorption of the photoactive sunlight component or on the deactivation of excited molecules that have already absorbed a light quantum, as well as on the inhibition of dark light-induced reactions. The work objective is to provide a comparative analysis of compounds of the sterically hindered phenols (SHP) series and nitroxide radicals (NR) as the PM photodegradation inhibitors.Materials and Methods. Reagents of the “purum” grade, LDPE premium grade 15803-020 polyethylene film were used for the investigations. The stabilizer was applied to the film by dipping. Carbonyl groups in polyethylene were determined by IR spectroscopy. IR spectra were recorded on Varian-640 instrument.Research Results. 2,4,6-tri-tert-amylphenol (1), 2-methyl-4,6-di-tert-butylphenol (2), 4-acetylamino-2,2,6,6-tetramethylpiperidin-1-oxyl (3), 3-carboxamido-2,2,5,5-tetramethylpyrrolin-1-oxyl (4) were tested as stabilizers for photo-oxidative degradation of polyethylene. It is known that the accumulation of carbonyl and hydroxyl groups is recorded in PM samples under irradiation in the process of photodegradation through the IR spectroscopy. The absorption band of the carbonyl group at 1720 cm- 1 appears in the IR spectra of oxidized polyethylene. The IR spectra analysis shows that the content of carbonyl groups in the check samples is significantly higher than in the samples treated by stabilizer solutions.Discussion and Conclusions. The experiments show that ni-troxide radicals of 3-carboxamido-2,2,5,5-tetramethylpyrrolin-1-oxyl series and 4-acetylamino-2,2,6,6-tetramethylpiperidin-1-oxyl are the best photostabilizers of polyethylene. Moreover, there is no significant difference between the radicals of the 2,2,6,6-tetramethylpiperidine and 2,2,5,5-tetramethylpyrroline series. Sterically hindered phenols, under photodegradation, have a far smaller stabilizing effect, falling short of nitroxide radicals.

This study focuses on analyzing the noncovalent interaction patterns between three lipid‐nanodisc‐forming polymers and nitroxide radicals which are used as small organic tracer molecules. Besides the negatively charged polymers diisobutylene/maleic acid (DIBMA) and styrene/maleic acid (SMA) (2:1), the solvation behavior of a newly synthesized zwitterionic styrene/maleic amide sulfobetaine copolymer named SMA‐sulfobetaine (SB) is characterized. The applied spin probes vary in their respective chemical structure, allowing the report of different local micropolarities and nanoscopic regions by recording temperature‐dependent continuous‐wave electron paramagnetic resonance (CW EPR) spectra. In combination with light scattering experiments, a nanoscopic interpretation of the dominant polymer/guest molecule interaction patterns is provided. The results indicate that in SMA and DIBMA, ionic interactions dominate the interaction patterns with other molecules. In SMA‐SB, the zwitterionic side chains mainly induce a dynamic assembly with guest molecules due to weaker noncovalent interactions. Depending on the applied spin probe, temperature‐dependent CW EPR measurements reveal nanoscopic cloud points depending on the interaction patterns with SMA‐SB which can occur more than 20 °C below its macroscopically observed upper critical solution temperature. Finally, the detailed dissection of interaction patterns may provide a better understanding that may even allow tuning the polymers' properties for use in lipid nanodisc formation. [ABSTRACT FROM AUTHOR]

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 HO 2 ∙ 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. [ABSTRACT FROM AUTHOR]

The reduction technique of 2,2,5,5-tetramethylpyrroline compounds to pyrrolidines on sodium amalgam preformed under the electrolysis of sodium hydroxide solution is described.

By the interaction of 2-bromo-4,4,5,5-tetramethyl-2-imidazoline-3-oxide-1-oxyl (NN–Br) with tetrakis(triphenylphosphine)palladium(0) a new paramagnetic palladium-organic compound [Pd(NN)(PPh3)2Br] is synthesized. The crystal structure of its tetrahydrofuran solvate is determined by X-ray diffraction. The obtained data allow us to expect that the effective Pd–C bond eclipsing by phenyl rings deactivates the compound in a cross-coupling reaction with aryl halides and provides its high kinetic stability under normal conditions. Magnetochemical studies show the presence of weak antiferromagnetic exchange interactions between spins of paramagnetic [Pd(NN)(PPh3)2Br]. [ABSTRACT FROM AUTHOR]

Poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) is a pH-sensitive polymer, while a few recent studies have shown it to possess temperature responsiveness as well. In this article, poly(2-(diethylamino)ethyl methacrylate-co-2,2,6,6-tetramethyl-4-piperidyl methacrylate)s, DEA-TMPMs, were synthesized. The TMPM moieties in DEA-TMPMs were subsequently oxidized with hydrogen peroxide to obtain poly(2-(diethylamino)ethyl methacrylate-co-2,2,6,6-tetramethylpiperidine-1-oxyl methacrylate), DEA-TMPs, having nitroxide radicals on the polymer chains. DEA-TMPMs were characterized by nuclear magnetic resonance spectroscopy, gel permeation chromatography, differential scanning calorimetry and thermogravimetry techniques, whereas DEA-TMPs were analyzed by Fourier transform infrared spectroscopy, cyclic voltammetry, and electron paramagnetic resonance (EPR) spectroscopy. The results showed that at low pH, the rotational mobility of nitroxide radicals was reduced as EPR spectra mostly consisted of slow-motion component. This slow-motion component in the EPR spectra remained unchanged below neutral pH. These results indicated a sort of interaction among nitroxide radicals and protonated amine groups of DEAEMA monomers. [ABSTRACT FROM AUTHOR]

EPR spectroscopic evidence for intramolecular electron transfer in anionic N‐substituted naphthalimides to yield persistent diradical anions and intermolecular electron transfer from a variety of carbanions to 6‐bromo‐N‐phenyl‐naphthalimide to yield persistent radical–radical anion pairs was recently claimed in two papers by Zhang et al. In this comment, it is shown that the EPR spectra published in both papers do not agree with the proposed triplet‐state species. Rather, the spectra are due to various doublet‐state radicals, deriving from minor side reactions. The misinterpretations invalidate the general conclusions of the papers. [ABSTRACT FROM AUTHOR]

Understanding the segmental dynamics of polymer chains is cardinal to decipher the microscopic behaviour in order to modulate the bulk properties of polymers. The study of electron spin resonance (ESR) spectroscopy of spin-labelled polymers is useful to understand the segmental dynamics of polymer chains in solution. In this paper, poly(acrylic acid)s (PAAs) were spin labelled with 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl radicals. Spin-labelled PAAs (SL-PAAs) were characterised by Fourier-transform infrared spectroscopy, ultraviolet–visible spectroscopy, thermogravimetric analysis, differential scanning calorimetry, cyclic voltammetry (CV), and ESR analyses. The polyelectrolyte complexes of SL-PAAs were prepared by employing poly(diallyldimethylammonium chloride) (PDADMAC) as the polycation and analysed by transmission electron microscopy, dynamic light scattering (DLS), and ESR spectroscopies. The effect of molar mass on the segmental dynamics of SL-PAAs in pristine as well as in the form of polyelectrolyte complexes (PECs) was studied. The results indicated that SL-PAAs show a differential complexation behaviour with PDADMAC in the PECs depending on their molar mass. [ABSTRACT FROM AUTHOR]

Nitroxide radicals are characterized by a long-lived open-shell electronic ground state and are strongly sensitive to the chemical environment, thus representing ideal spin probes and spin labels for paramagnetic biomolecules and materials. However, the interpretation of spectroscopic parameters in structural and dynamic terms requires the aid of accurate quantum chemical computations. In this paper we validate a computational model rooted into double-hybrid functionals and second order vibrational perturbation theory. Then, we provide reference quantum chemical results for the structures, vibrational frequencies and other spectroscopic features of a large panel of nitroxides of current biological and/or technological interest.

Psychomotor stimulants are the most commonly used prohibited substances after cannabis. Globally, their use reaches epidemiological proportions and is one of the most common causes of death in many countries. The use of illicit drugs has negative effects on the cardiovascular system and is one of the causes of serious cardiovascular pathologies, ranging from abnormal heart rhythms to heart attacks and sudden cardiac death. The reactive oxygen species generation, toxic metabolites formation, and oxidative stress play a significant role in cocaine-induced cardiotoxicity. The aim of the present review is to assess acute and chronic cocaine toxicity by focusing on the published literature regarding oxidative stress levels. Hypothetically, this study can serve as a basis for developing a rapid and effective method for determining oxidative stress levels by monitoring changes in the redox status of patients with cocaine intoxication.

Abstract—This review is devoted to the electron paramagnetic resonance (EPR) studies of porous polymer materials (matrixes) made of aliphatic polyesters and doped with paramagnetic biologically active substances using supercritical fluid technologies. Particular attention is paid to the possibilities of EPR spectroscopy for establishing the regularities of the formation of the matrixes, subsequent characterization of the materials obtained, and features of the dopant release to aqueous solutions in vitro. [ABSTRACT FROM AUTHOR]

A method for the synthesis of solvates of dinuclear heterospin complexes of bis(hexafluoroacetylacetonato)copper(ii) with 2-(4-methylpyridin-3-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (LMe) and 2-(4-ethylpyridin-3-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (LEt) of the composition [Cu(hfac)2LR]2 · Solv (Solv = benzene, bromobenzene, toluene, o-xylene, p-xylene) was developed. It was found that a decrease in temperature induces structural transformations of the solid phases of the complexes followed by significant changes in the distances between the paramagnetic centers in the intramolecular exchange clusters {Cu2+-O·-} from 2.321 to 1.974 Å. As a result, the temperature dependences of the effective magnetic moment μeff(T) exhibit magnetic features similar to spin transitions. An analysis of the shape of the μeff(T) curves suggested that the magnetic properties of the compounds under study depend primarily on the molecular packing. A comparison of the magneto-structural correlations typical of the [Cu(hfac)2LR]2 · Solv complexes studied in this work with the data obtained earlier for analogous solvates of heterospin polymer chain complexes showed that the spin transition characteristics of the [Cu(hfac)2LR]2 · Solv systems are much less sensitive to the change of the solvent than the corresponding characteristics of the heterospin polymers containing solvate molecules in the interchain space. The magnetic characteristics of the heterospin dimer molecules depend primarily on which cavity between the dimers is filled with solvate molecules. For solvates with monoclinic symmetry, changes in the solvent molecules occupying same-type cavities have almost no effect on the spin transition characteristics in the heterospin exchange cluster. [ABSTRACT FROM AUTHOR]

Abstract Relative diffusion of free radicals in solution modulates the Heisenberg spin exchange and dipole-dipole interactions among them, which affects their electron paramagnetic resonance (EPR) spectra. The radical concentration dependence of EPR parameters can, in turn, give information about radical diffusivity in a liquid. We studied the diffusivities of the 14N- and 15N-labeled perdeuterated TEMPONE radicals at various temperatures in three viscous liquids: 1‑ethyl‑3‑methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquid, propylene carbonate, and ethylene glycol. By fitting EPR spectra at various radical concentrations, we obtained the concentration coefficients of EPR parameters. The concentration coefficients were related to the radical diffusivity by solving the kinetic equations for the spin evolution of a radical pair, considering the radicals as continuously diffusing spherical objects in the hard-core pair potential. We tested the method by comparing the calculated radical diffusivities of isotopically substituted TEMPONE radicals. Temperature dependences of radical diffusivities were discussed in terms of the Stokes-Einstein relation. Additionally, the radical diffusivities were compared to the self-diffusivities of the studied liquids. At lower temperatures, the radical diffusivities follow the self-diffusivities, while at the higher temperatures, the radical diffusivities start deviating from the self-diffusivities. Graphical abstract Unlabelled Image Highlights • The radical diffusivities of 14N- and 15N-labeled perdeuterated TEMPONE were studied by EPR in three viscous liquids • Diffusivities were obtained from concentration coefficients of EPR parameters by solving kinetic equations of radical pairs • The deviations of the temperature dependences of radical diffusivities from the Stokes-Einstein relation were discussed • Radical diffusivities were found to conform with the self-diffusivities of the studied liquids with decreasing temperature [ABSTRACT FROM AUTHOR]

β‐Peptides are an interesting new class of transmembrane model peptides based on their conformationally stable and well‐defined secondary structures. Herein, we present the synthesis of the paramagnetic β‐amino acid β3‐hTOPP (4‐(3,3,5,5‐tetramethyl‐2,6‐dioxo‐4‐oxylpiperazin‐1‐yl)‐d‐β3‐homophenylglycine) that enables investigations of β‐peptides by EPR spectroscopy. This amino acid adds to the, to date, sparse number of β‐peptide spin labels. Its performance was evaluated by investigating the helical turn of a 314‐helical transmembrane model β‐peptide. Nanometer distances between two incorporated β3‐hTOPP labels in different environments were measured by using pulsed electron/electron double resonance (PELDOR/DEER) spectroscopy. Due to the semi‐rigid conformational design, the label delivers reliable distances and sharp (one‐peak) distance distributions even in the lipid bilayer. The results indicate that the investigated β‐peptide folds into a 3.2514 helix and maintains this conformation in the lipid bilayer. Nitroxide radicals: New semi‐rigid spin label β3‐hTOPP has allowed the investigation of a β‐peptide structure by EPR spectroscopy. Well‐defined inter‐spin distances between two β3‐hTOPP labels in a model β‐peptide have been measured in lipid bilayers using pulsed electron/electron double resonance (PELDOR) spectroscopy. The labelling strategy has permitted to determine the peptide helical structure with resolution at molecular‐length scale (see figure). [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Oxidizing agent K 3 Fe(CN) 6 slows reduction of protein-bound 5-MSL in cells. • Increased protein concentration extends lifetime of doubly 5-MSL labeled GB1. • Nitroxide DEER acquired after unprecedented 3-h incubation in-cell and 5-h in cytosol. • Room temperature continuous wave experiments are possible in Xenopus laevis oocytes. Abstract There is increasing evidence that the stability, structure, dynamics, and function of many proteins differ in cells versus in vitro. The determination of protein structure and dynamics within the native cellular environment may lead to better understanding of protein behavior. Electron spin resonance (ESR) has emerged as a technique that can report on protein structure and dynamics within cells. Nitroxide based spin labels are capable of reporting on protein dynamics, structure, and backbone flexibility but are limited due to nitroxide reduction occurring in cells. In order to overcome this limitation, we used the oxidizing agent potassium ferricyanide (K 3 Fe(CN) 6) as well as the cleavage resistant spin label 3-malemido-PROXYL (5-MSL). Furthermore, we hypothesized that injection concentration is an important parameter regarding nitroxide reduction kinetics. By increasing the injection concentration of doubly 5-MSL labeled protein into Xenopus laevis oocytes, we found an increased nitroxide lifetime. Our work demonstrates unprecedented incubation times of 3-h in-cell and 5-h in-cytosol for double electron–electron resonance (DEER) experiments using nitroxide spin labels. This allows for more meaningful measurements of larger protein systems which may require longer incubation times for equilibration in the cellular milieu. Even longer incubation times are possible by combining our approach with more shielded nitroxides and Q-band. [ABSTRACT FROM AUTHOR]

Liquid crystalline (LC) organic radicals were expected to show a novel non-linear magnetic response to external magnetic and electric fields due to their coherent collective molecular motion. We have found that a series of chiral and achiral all-organic LC radicals having one or two five-membered cyclic nitroxide radical (PROXYL) units in the core position and, thereby, with a negative dielectric anisotropy exhibit spin glass (SG)-like superparamagnetic features, such as a magnetic hysteresis (referred to as ‘positive magneto-LC effect’), and thermal and impurity effects during a heating and cooling cycle in weak magnetic fields. Furthermore, for the first time, a nonlinear magneto-electric (ME) effect has been detected with respect to one of the LC radicals showing a ferroelectric (chiral Smectic C) phase. The mechanism of the positive magneto-LC effect is proposed and discussed by comparison of our experimental results with the well-known magnetic properties of SG materials and on the basis of the experimental results of a nonlinear ME effect. A recent theoretical study by means of molecular dynamic simulation and density functional theory calculations suggesting the high possibility of conservation of the memory of spin-spin interactions between magnetic moments owing to the ceaseless molecular contacts in the LC and isotropic states is briefly mentioned as well.

Four albumin-nitroxide conjugates were prepared and tested as metal-free organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI). Each human serum albumin (HSA) carrier bears multiple nitroxides conjugated via homocysteine thiolactones. These molecular conjugates retain important physical and biological properties of their HSA component, and the resistance of their nitroxide groups to bioreduction was retained or enhanced. The relaxivities are similar for these four conjugates and are much greater than those of their individual components: the HSA or the small nitroxide molecules. This new family of conjugates has excellent prospects for optimization as ORCAs.

This Correspondence reports on a structural and mechanistic misinterpretation of an observed EPR spectrum, a misleading presentation of DNA cleavage data, and the physicochemically unsupported assignment of nitric oxide as a major DNA cleaving agent in the article cited in the title. [ABSTRACT FROM AUTHOR]

A substrate‐independent and versatile coating platform for (spatially resolved) surface functionalization, based on nitroxide radical coupling (NRC) reactions and the formation of thermo‐labile alkoxyamine functional groups, was introduced. Nitroxide‐decorated poly(glycidyl methacrylate) (PGMA) microspheres, obtained through bioinspired copolymer surface deposition using dopamine and a nitroxide functional dopamine derivative as monomers, were conjugated with small functional groups in a rewritable process. Reversible coding of the nitroxide functional microspheres by NRC and decoding through thermal alkoxyamine fission were monitored and characterized by electron paramagnetic resonance (EPR) spectroscopy and X‐ray photoelectron spectroscopy (XPS). In addition, this nitroxide coating system was exploited in "grafting‐to" polymer surface ligations of poly(methyl methacrylate) (PMMA) and poly(2,2,2‐trifluoroethyl methacrylate) (PTFEMA) in spatially confined areas. Polymer strands terminated with an Irgacure 2959 (2‐hydroxy‐4′‐(2‐hydroxyethoxy)‐2‐methylpropiophenone) photoinitiator were obtained through chain‐transfer polymerization, and subsequently coupled to nitroxide‐immobilized poly(dopamine) (PDA)‐coated silicon substrates by using rapid photoclick NRC reactions. Light‐driven polymer surface coding was visualized by time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) and XPS imaging. Coating with nitroxide: A versatile, bioinspired nitroxide functional coating platform is presented for precise programming of various materials. Nitroxide‐coated polymeric microspheres with rewritable properties were manufactured, exemplified in consecutive nitroxide radical coupling (coding) and thermal alkoxyamine fission (decoding) reaction steps. Photoinduced dual‐polymer‐patterned surfaces were further generated highlighting the broad applicability of our nitroxide coating system. [ABSTRACT FROM AUTHOR]

In this review on advanced biomolecular EPR spectroscopy, which addresses both the EPR and NMR communities, considerable emphasis is put on delineating the complementarity of NMR and EPR regarding the measurement of interactions and dynamics of large molecules embedded in fluid-solution or solid-state environments. Our focus is on the characterization of protein structure, dynamics and interactions, using sophisticated EPR spectroscopy methods. New developments in pulsed microwave and sweepable cryomagnet technology as well as ultrafast electronics for signal data handling and processing have pushed the limits of EPR spectroscopy to new horizons reaching millimeter and sub-millimeter wavelengths and 15 T Zeeman fields. Expanding traditional applications to paramagnetic systems, spin-labeling of biomolecules has become a mainstream multifrequency approach in EPR spectroscopy. In the high-frequency/high-field EPR region, sub-micromolar concentrations of nitroxide spin-labeled molecules are now sufficient to characterize reaction intermediates of complex biomolecular processes. This offers promising analytical applications in biochemistry and molecular biology where sample material is often difficult to prepare in sufficient concentration for NMR characterization. For multifrequency EPR experiments on frozen solutions typical sample volumes are of the order of 250 L (S-band), 150 L (X-band), 10 L (Q-band) and 1 L (W-band). These are orders of magnitude smaller than the sample volumes required for modern liquid- or solid-state NMR spectroscopy. An important additional advantage of EPR over NMR is the ability to detect and characterize even short-lived paramagnetic reaction intermediates (down to a lifetime of a few ns). Electron-nuclear and electron-electron double-resonance techniques such as electron-nuclear double resonance (ENDOR), ELDOR-detected NMR, PELDOR (DEER) further improve the spectroscopic selectivity for the various magnetic interactions and their evolution in the frequency and time domains. PELDOR techniques applied to frozen-solution samples of doubly spin-labeled proteins allow for molecular distance measurements ranging up to about 100 Å. For disordered frozen-solution samples high-field EPR spectroscopy allows greatly improved orientational selection of the molecules within the laboratory axes reference system by means of the anisotropic electron Zeeman interaction. Single-crystal resolution is approached at the canonical g-tensor orientations--even for molecules with very small g-anisotropies. Unique structural, functional, and dynamic information about molecular systems is thus revealed that can hardly be obtained by other analytical techniques. On the other hand, the limitation to systems with unpaired electrons means that EPR is less widely used than NMR. However, this limitation also means that EPR offers greater specificity, since ordinary chemical solvents and matrices do not give rise to EPR in contrast to NMR spectra. Thus, multifrequency EPR spectroscopy plays an important role in better understanding paramagnetic species such as organic and inorganic radicals, transition metal complexes as found in many catalysts or metalloenzymes, transient species such as light-generated spin-correlated radical pairs and triplets occurring in protein complexes of photosynthetic reaction centers, electron-transfer relays, etc. Special attention is drawn to high-field EPR experiments on photosynthetic reaction centers embedded in specific sugar matrices that enable organisms to survive extreme dryness and heat stress by adopting an anhydrobiotic state. After a more general overview on methods and applications of advanced multifrequency EPR spectroscopy, a few representative examples are reviewed to some detail in two Case Studies: (I) High-field ELDOR-detected NMR (EDNMR) as a general method for electron-nuclear hyperfine spectroscopy of nitroxide radical and transition metal containing systems; (II) High-field ENDOR and EDNMR studies of the Oxygen Evolving Complex (OEC) in Photosystem II, which performs water oxidation in photosynthesis, i.e., the light-driven splitting of water into its elemental constituents, which is one of the most important chemical reactions on Earth. [ABSTRACT FROM AUTHOR]

The cytotoxicity and antioxidant properties of water-soluble (at physiological pH) chitosan- (poly)nitroxides (CPNs) containing pyrroline-based nitroxide and having different molecular weights of the polysaccharide backbone were studied on normal (Vero) and tumor (HepG2) cell models. The compounds were found to exhibit low cytotoxicity and to effectively reduce the level of reactive oxygen species (ROS) generated upon the breakdown of tert-butyl hydroperoxide in normal cells. In tumor cells, the CPNs have little effect on the ROS level under the oxidative stress. The results show that CPNs also represent a promising platform for the development of cell delivery systems for biologically active compounds. [ABSTRACT FROM AUTHOR]

Five new ionic conjugates based on α-tocopheryl succinate were synthesized, including amino- TEMPO, cytisine, convolvin, amantadine, and rimantadine as functional groups. Using bacterial test systems, the safety of the compounds obtained was shown, and antioxidant properties were studied. Investigation of the cytotoxic properties of synthesized conjugates with a chromane skeleton revealed their selectivity to the MCF7 breast cancer line, the effect was most pronounced for derivatives with amino-TEMPO and rimantadine fragments. [ABSTRACT FROM AUTHOR]

[Display omitted] A one-stage synthesis of paramagnetic Re(I) compounds based on the reaction of [Re(CO) 5 Br] with spin-labeled N -donor heterocycles was developed. Nitronyl nitroxide derivatives of 1 H- imidazole (L1), 1 H- pyrazole (L2), di(1 H -pyrazol-1-yl)methane (L3) and 4-methyl-2-(1 H -pyrazol-1-yl)quinoline (L4) can easily substitute two coordinated CO molecules in [Re(CO) 5 Br], resulting in a series of paramagnetic fac- [Re(CO) 3 (L i) n Br]· x Solv complexes. Single crystal XRD studies showed that the paramagnetic L1-L4 ligands are coordinated by Re(I) through the imine atoms N of the heterocycles. According to SQUID measurements and EPR spectroscopy data, magnetic behavior of [Re(CO) 3 (L1) 2 Br] (1), [Re(CO) 3 (L2) 2 Br] (2), and [Re(CO) 3 (L3)Br] (3) complexes are typical for biradicals, while [Re(CO) 3 (L4)Br] (4) is typical for monoradical. The combination of Re(I) therapeutic properties and contrasting characteristics of nitroxide radicals in diagnostic magnetic resonance imaging, stability and simplicity of synthesis make [Re(CO) 3 (L i) n Br] valuable model objects for material design for theranostics purposes. [ABSTRACT FROM AUTHOR]