Cyclic Hydroxylamines as Monitors of Peroxynitrite and Superoxide-Revisited

There is a considerable need for methods that allow quantitative determination in vitro and in vivo of transient oxidative species such as peroxynitrite (ONOOH/ONOO–) and superoxide (HO2•/O2•−). Cyclic hydroxylamines, which upon oxidation yield their respective stable nitroxide radicals, have been suggested as spin probes of peroxynitrite and superoxide. The present study investigated this approach by following the kinetics of peroxynitrite decay in the absence and presence of various 5-membered and 6-membered ring hydroxylamines, and comparing the yield of their respective nitroxides using electron paramagnetic spectroscopy. The results demonstrate that hydroxylamines do not react directly with peroxynitrite, but are oxidized to their respective nitroxides by the radicals formed during peroxynitrite self-decomposition, namely •OH and •NO2. The accumulated nitroxides are far below their expected yield, had the hydroxylamines fully scavenged all these radicals, due to multiple competing reactions of the oxidized forms of the hydroxylamines with •NO2 and ONOO–. Therefore, cyclic hydroxylamines cannot be used for quantitative assay of peroxynitrite in vitro. The situation is even more complex in vivo where •OH and •NO2 are formed also via other oxidizing reactions systems. The present study also compared the yield of accumulated nitroxides under constant flux of superoxide in the presence of various cyclic hydroxylamines. It is demonstrated that certain 5-membered ring hydroxylamines, which their respective nitroxides are poor SOD-mimics, might be considered as stoichiometric monitors of superoxide in vitro at highest possible concentrations and pH.

Application of Redox-Responsive Hydrogels Based on 2,2,6,6-Tetramethyl-1-Piperidinyloxy Methacrylate and Oligo(Ethyleneglycol) Methacrylate in Controlled Release and Catalysis

Hydrogels have reached momentum due to their potential application in a variety of fields including their ability to deliver active molecules upon application of a specific chemical or physical stimulus and to act as easily recyclable catalysts in a green chemistry approach. In this paper, we demonstrate that the same redox-responsive hydrogels based on polymer networks containing 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) stable nitroxide radicals and oligoethylene glycol methyl ether methacrylate (OEGMA) can be successfully used either for the electrochemically triggered release of aspirin or as catalysts for the oxidation of primary alcohols into aldehydes. For the first application, we take the opportunity of the positive charges present on the oxoammonium groups of oxidized TEMPO to encapsulate negatively charged aspirin molecules. The further electrochemical reduction of oxoammonium groups into nitroxide radicals triggers the release of aspirin molecules. For the second application, our hydrogels are swelled with benzylic alcohol and tert-butyl nitrite as co-catalyst and the temperature is raised to 50 °C to start the oxidation reaction. Interestingly enough, benzaldehyde is not miscible with our hydrogels and phase-separate on top of them allowing the easy recovery of the reaction product and the recyclability of the hydrogel catalyst.

Re(i)-nitroxide complexes

Stable nitroxide-substituted cyrhetrenes were synthesized and characterized by EPR, CV, XRD, magnetochemistry and quantum chemistry methods.

Characterization of Aqueous Lower Polarity Solvation Shells Around Amphiphilic TEMPO Radicals in Water

Solvation of the stable nitroxide radicals 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) and 4-Oxo-TEMPO (TEMPONE) in water and THF is studied. With electron paramagnetic resonance (EPR) spectroscopy at X- and Q-band as well as spectral simulations, the existence of pure water shells enclosing TEMPO in aqueous solution that lead to significantly reduced local polarity at the nitroxide is shown. These aqueous lower polarity solvation shells (ALPSS) offer TEMPO a local polarity that is similar to that in organic solvents like THF. Furthermore, using double electron-electron resonance (DEER) spectroscopy, local enrichment and inhomogenous distribution without collisions of dissolved TEMPO in water is found that can be correlated with potentially attractive interactions mediated through ALPSS. However, no local enrichment of TEMPO is found in organic solvents such as THF. These results are substantiated by MD and metadynamics simulations and physical methods like DLS and MS.

Characterization of Aqueous Lower Polarity Solvation Shells Around Amphiphilic TEMPO Radicals in Water

Solvation of the stable nitroxide radicals 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) and 4-Oxo-TEMPO (TEMPONE) in water and THF is studied. With electron paramagnetic resonance (EPR) spectroscopy at X- and Q-band as well as spectral simulations, the existence of pure water shells enclosing TEMPO in aqueous solution that lead to significantly reduced local polarity at the nitroxide is shown. These aqueous lower polarity solvation shells (ALPSS) offer TEMPO a local polarity that is similar to that in organic solvents like THF. Furthermore, using double electron-electron resonance (DEER) spectroscopy, local enrichment and inhomogenous distribution without collisions of dissolved TEMPO in water is found that can be correlated with potentially attractive interactions mediated through ALPSS. However, no local enrichment of TEMPO is found in organic solvents such as THF. These results are substantiated by MD and metadynamics simulations and physical methods like DLS and MS.

It takes two for chronic wounds to heal: dispersing bacterial biofilm and modulating inflammation with dual action plasma coatings

We plasma polymerized the stable nitroxide radical TEMPO into thin coatings and exploited the coatings' unique qualities in targeting both infection and inflammation simultaneously; demonstrating a novel alternative as to how chronic wounds could be treated in the future.

Assessment of the Relaxation-Enhancing Properties of a Nitroxide-Based Contrast Agent TEEPO-Glc with In Vivo Magnetic Resonance Imaging

Magnetic resonance imaging examinations are frequently carried out using contrast agents to improve the image quality. Practically all clinically used contrast agents are based on paramagnetic metals and lack in selectivity and specificity. A group of stable organic radicals, nitroxides, has raised interest as new metal-free contrast agents for MRI. Their structures can easily be modified to incorporate different functionalities. In the present study, a stable nitroxide TEEPO (2,2,6,6-tetraethylpiperidin-1-oxyl) was linked to a glucose moiety (Glc) to construct a water-soluble, potentially tumor-targeting compound with contrast-enhancing ability. The ability was assessed with in vivo MRI experiments. The constructed TEEPO-Glc agent proved to shorten the T1 relaxation time in tumor, while the T1 time in healthy brain tissue remained the same. The results indicate the potential of TEEPO-Glc as a valuable addition to the growing field of metal-free contrast enhancement in MRI-based diagnostics.

A Theoretical and Experimental Study for Screening Inhibitors for Styrene Polymerization

Styrene is one of the most important monomers utilized in the synthesis of various polymers. Nevertheless, during distillation, storage, and transportation of ST, undesired polymer (i.e., UP) formation can take place. Thus, the control of undesired polymerization of styrene is a challenging issue facing industry. To tackle the mentioned issue, the antipolymer and antioxidant activity of stable nitroxide radicals (i.e., SNRs) and phenolics in styrene polymerization were studied by density functional theory (DFT) calculation and experimental approach. The electrophilicity index and growth percentage have been determined by DFT calculation and experimental approach, respectively. It is depicted that 2,6-di-tert-butyl-4-methoxyphenol (DTBMP) and 2,6-di-tert-butyl-4-methylphenol (BHT) from phenolics, and 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-Oxyl (4-hydroxy-TEMPO) and 4-oxo-2,2,6,6-tetramethylpiperidine 1-Oxyl (4-oxo-TEMPO) from stable nitroxide radicals were the most effective inhibitors. Also, the growth percentage of DTMBP, BHT, 4-hydroxy-TEMPO, and 4-oxo-TEMPO after 4 h were 16.40, 42.50, 24.85, and 46.8, respectively. In addition, the conversion percentage of DTMBP, BHT, 4-hydroxy-TEMPO, and 4-oxo-TEMPO after 4 h were obtained to be 0.048, 0.111, 0.065, and 0.134, respectively. Furthermore, the synergistic effect of these inhibitors was investigated experimentally, indicating that DTMBP/4-hydroxy-TEMPO exerted the best synergistic effects on the inhibition of polymerization. The optimum inhibition effect was observed at the blend of 4-hydroxy-TEMPO (25 wt.%) and DTMBP (75 wt.%,) corresponding to 6.8% polymer growth after 4 h.

Ion-Conducting Redox-Active Polymer Gels Based on Stable Nitroxide Radicals

Redox-active polymer networks based on stable nitroxide radicals are a very promising class of materials to be used in the so-called organic radical batteries. In order to obtain fast-charging and high power electrodes, however, excellent ionic conductivity inside the electrode material is required to allow easy diffusion of ions and fast redox reactions. In this contribution, we investigated redox-active poly(2,2,6,6-tetramethylpiperidinyloxy-4-yl methacrylate) chains cross-linked through ionic liquid-like 1,2,3-triazolium groups. Different networks were prepared in which the amount of cross-linker and the counter-anion associated to the 1,2,3-triazolium group were varied. The ionic conductivities of the different polymer networks were first measured in the solid state by electrochemical impedance spectroscopy at different temperatures, and an increased ionic conductivity was measured when 1,2,3-triazolium groups were present in the network. The effects of the chemical nature of the counterions associated to the 1,2,3-triazolium groups and of the crosslinking density were then studied. The best ionic conductivities were obtained when bis (trifluoromethane)sulfonamide (TFSI) counter-anions were used, and when the crosslinking density of the TFSI-containing gel was higher. Finally, those ion-conducting gels were loaded with free LiTFSI and the transference number of lithium ions was accordingly measured. The good ionic conductivities and lithium ions transference numbers measured for the investigated redox-active gels make them ideal candidates for application as electrode materials for either organic radical batteries or pseudo-capacitors energy storage devices.