Radical Mediators Research Articles

Unveiling the critical role of crystallinity in photogenerated hole transfer behavior of TiO2 with an aminoxyl radical mediator

Integrating aminoxyl radical mediators (ARMs) with titanium dioxide (TiO2) based photoelectrochemical (PEC) processes presents a promising approach for achieving mild and sustainable chemical transformations. However, a comprehensive understanding of the interaction between ARMs and PEC processes remains elusive. This study investigates the PEC behavior of photoelectrodes fabricated from single- and polycrystalline TiO2 in the presence of a representative ARM, 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl radical, in acetonitrile. Interestingly, we observe contrasting PEC behavior: photocurrent enhancement for single-crystalline TiO2 and photocurrent suppression for polycrystalline TiO2. We attribute this difference to subtle variations in surface properties arising from the material’s crystallinity. Photoelectrochemical impedance spectroscopy (PEIS) is employed to gain deeper insights into the influence of surface defects on charge transfer and recombination mechanisms. The PEIS results suggest that an anomalous hole transfer mechanism mediated by surface trap states governs the PEC performance of polycrystalline TiO2.

Selective Electrochemical Oxidation of Benzylic C-H to Benzylic Alcohols with the Aid of Imidazolium Radical Mediators.

Selective oxidation of benzylic C-H to benzylic alcohols is a well-known challenge in the chemical community since benzylic C-H is more prone to be overoxidized to benzylic ketones. In this work, we report the highly selective electro-oxidation of benzylic C-H to benzylic alcohols in an undivided cell in ionic liquid-based solution. As an example, the selectivity toward xanthydrol could be as high as 95.7% at complete conversion of xanthene, a typical benzylic C-H compound, on gram-scale in imidazolium bromide/H2O/DMF. Mechanism investigation reveals that the imidazolium radical generated in situ participants in a proton-coupled electron transfer process and low-barrier hydrogen bonds stabilize the reaction intermediates, together steering the redox equilibrium, favoring benzylic alcohols over benzylic ketones.

Electrochemical Characterization of the Laccase-Catalyzed Oxidation of 2,6-Dimethoxyphenol: an Insight into the Direct Electron Transfer by Enzyme and Enzyme-Mediator System.

The oxidation process of 2,6-dimethoxyphenol (2,6-DMP) by laccase from Botryosphaeria rhodina MAMB-05 and the corresponding enzyme-mediator systems was studied using cyclic voltammetry (CV). The enzyme was classified as a high oxidation potential laccase (> 0.70) V vs. NHE) based on its Redox potential at different pHs. The cyclic voltammograms for 2,6-DMP (- 58.7mV pH-1) showed that its oxidation potential decreased more significantly compared to the enzyme (- 50.2mV pH-1) by varying the pH. The 2,2'-azino-bis[3-ethyl-benzothiazoline-6-sulfonic acid] diammonium salt (ABTS) and 2,2,6,6-tetramethylpiperidine 1-oxyl radical (TEMPO) mediators were effectively oxidized by laccase from B. rhodina MAMB-05. The influence of laccase on the comproportionation of ABTS and the ionic step of the oxidation of TEMPO was also studied using CV. A higher potential difference was observed between laccase and the substrate, and correlated with higher enzyme activity. For the laccase-mediator systems, there was no clear correlation of potential difference between laccase and mediators with enzyme activity towards 2,6-DMP. This observation suggests that there are other limiting parameters for enzyme activity despite Redox potential difference, especially during ionic steps of the mechanism.

Modulation of dual centers on cobalt-molybdenum oxides featuring synergistic effect of intermediate activation and radical mediator for electrocatalytic urea splitting

Construction of dual sites to break adsorption-energy scaling limitations offers an effective means of facilitating urea electrolysis for H 2 production, but a fundamental understanding of their synergistic mechanisms remains incomplete. Herein, we report a facile H 2 vapor-assisted strategy for the controllable fabrication of the bimetallic active Co 2 Mo 3 O 8 electrocatalyst for alkaline urea splitting, with an applied voltage of only 1.50 V required to deliver 50 mA cm −2 . Direct spectroscopic evidence and theoretical investigation demonstrate that the Co sites are responsible for the activation of intermediates, whereas the assisting Mo centers are identified as the OH or H radical mediators. Specifically, the synergistic effect of the Co–Mo dual sites was conclusively verified by the in-situ Raman and X­ray photoelectron spectroscopy. Theoretical calculations reveal that the short H-bonding (Mo-HO∙∙∙H–N amine CO–Co) and Co–C–N–Mo configuration formed at the Co–Mo bridge are the key features determining a high reactivity for urea oxidation. The accelerated reaction rate is attributable to the conversion of the endoergic CO 2 desorption to an exoergic reaction. In an alkaline H 2 evolution, Co atoms are the reaction sites for O–H bond cleavage of H 2 O, while Mo sites are considered to be the H 2 -evolving centers. Determination of the individual functionality of synergistic dual centers represents a critical step towards the rational design of highly-efficient electrocatalysts. • We report a facile H 2 vapor-assisted strategy for the fabrication of the Co 2 Mo 3 O 8 catalyst for the alkaline urea splitting. • In situ reconstructed Co 3 O 4 and high-valence Mo (VI) species on the surface are responsible for increased urea oxidation. • The short H-bonding and Co-C-N-Mo configuration are the key features determining a high reactivity for urea oxidation. • In an alkaline HER, Co atom accounts for cleavage of H-OH bond, while Mo site is identified as the H 2 -evolving center.

Chemoselective Electrochemical Oxidation of Secondary Alcohols Using a Recyclable Chloride-Based Mediator

AbstractSelective anodic oxidation of alcohols in the presence of other functional groups can be accomplished by using nitroxyl radical mediators. However, the electrochemical chemoselective oxidation of secondary alcohols in the presence of primary alcohols is an unsolved issue. Herein, we report an electrochemical procedure for the selective oxidation of secondary alcohols by using an inexpensive chloride salt that acts as a redox mediator and supporting electrolyte. The method is based on the controlled anodic generation of active chlorine species, which selectively oxidize secondary alcohols to the corresponding ketones when primary hydroxy groups are present. The method has been demonstrated for a variety of substrates. The corresponding ketones were obtained in good to excellent yields. Moreover, the chloride salt can be easily recovered by a simple extraction procedure for reuse, rendering the method highly sustainable.

Sodium Thiophosphate Cathodes and Polymeric Membranes for High Energy Density Redox Flow Batteries

Redox flow batteries (RFBs) are promising energy storage devices for grid-level applications due to their long cycle life and the ability to independently scale their energy and power densities. The energy density of conventional RFBs is dictated by their capacity (which is directly related to the solubility of the redox species in the electrolyte) and operating potential. Aqueous RFBs generally have low operating potentials ca. 1.5 V, resulting in poor energy densities (25 – 30 Wh/kg for an all vanadium RFB), whereas systems containing organic electrolytes with wider electrochemical windows have moderately higher energy densities. Our team recently demonstrated proof-of-concept for a revolutionary approach which uses mediated electrochemical reactions in a RFB configuration to drive reversible Na storage in a red P anode. Extremely high capacities ~1,000 mAh/gP have been demonstrated using this method. In this configuration, the anion radical mediators are recycled several times throughout the cell stack during a single charge/discharge cycle, effectively decoupling the RFB’s energy density from the redox species’ solubility in the electrolyte. By pairing this mediated red P anode with a sulfide-based cathode, energy densities up to 200 Wh/kg (~10x that of conventional RFBs) can potentially be achieved. This presentation will describe our recent progress developing polymer membranes and high energy density cathodes/catholytes for RFBs. The preparation and characterization of ionically conductive, mechanically robust poly(ethylene oxide) (PEO)-based membranes which are chemically resistant to and prevent crossover of the radical mediators will be discussed. The synthesis and electrochemical properties of a new class of high energy density sodium thiophosphate cathodes for RFBs will also be provided. Acknowledgements This research is supported by Dr. Imre Gyuk, Manager, Energy Storage Program, Office of Electricity Delivery and Reliability, U.S. Department of Energy and the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy.

Use of Imidoxyl Radical Mediators for Electrochemical Oxidation/Depolymerization of Lignin

Lignin is an abundantbiopolymer with aromatic subunits in itsbackbone, and depolymerizationof this polymer could provide a source of valuable aromatic chemicals. The beta-O-4 unit, which features secondary benzylic and primary aliphatic alcohols (Figure 1), is the most prevalent linkage in the structure of lignin, and its cleavage provides high yields of aromatic monomers. The hydroxyl functional groups within this linkage are susceptible to oxidation, and their controlled oxidationprovides the basis for lignin depolymerization.[i]We have shown previously that the benzylic alcohol in lignin undergoes selective oxidation with an aminoxyl/NOxcocatalyst system under aerobic conditions. Subsequent treatment of the oxidized lignin with formic acid affords high yields of aromatic monomers.[ii]This talk will describe a complementary electrochemical method for selective oxidation of the benzylic alcohols in lignin. N-Hydroxyimide derivatives undergo facile proton coupled electron transfer at electrode surfaces to generate an imidoxyl radical that promotes efficient hydrogen atom transfer from the of benzylic hydroxyl groups.[iii]Our advances in the use of electrochemically generated imidoxyl radicals for chemoselective oxidation of hydroxyl groups in the structure of lignin will be presented. Benzylic alcohol oxidation proceeds efficiently to the corresponding ketones using imidoxyl radicals as electrocatalyst in water/acetone as solvent and with acetic acid/acetate as buffer and supporting electrolyte. Treatment of the oxidized lignin with formic acid affords more than 30 wt% of monomeric aromatic compounds. [i]. Li,C.; Zhao,X.; Wang,A.; Huber, G.W.; Zhang T. Chem. Rev. 2015,115, 11559. [ii]. Rahimi, A.; Ulbrich, A.; Coon, J. J.; Stahl S. S.Nature 2014, 515, 249. [iii]. Nutting, J. E.; Rafiee, M. R.; Stahl, S. S. Chem. Rev. 2018, 118, 4834. Figure 1. Imidoxyl catalyzed electrochemical oxidation of lignin followed by formic acid catalyzed depolymerization. Figure 1

Eco-friendly and facile integrated biological-cum-photo assisted electrooxidation process for degradation of textile wastewater

The present article reports an integrated treatment method viz biodegradation followed by photo-assisted electrooxidation, as a new approach, for the abatement of textile wastewater. In the first stage of the integrated treatment scheme, the chemical oxygen demand (COD) of the real textile effluent was reduced by a biodegradation process using hydrogels of cellulose-degrading Bacillus cereus. The bio-treated effluent was then subjected to the second stage of the integrated scheme viz indirect electrooxidation (InDEO) as well as photo-assisted indirect electro oxidation (P-InDEO) process using Ti/IrO2–RuO2–TiO2 and Ti as electrodes and applying a current density of 20 mA cm−2. The influence of cellulose in InDEO has been reported here, for the first time. UV–Visible light of 280–800 nm has been irradiated toward the anode/electrolyte interface in P-InDEO. The effectiveness of this combined treatment process in textile effluent degradation has been probed by chemical oxygen demand (COD) measurements and 1H – nuclear magnetic resonance spectroscopy (NMR). The obtained results indicate that the biological treatment allows obtaining a 93% of cellulose degradation and 47% of COD removal, increasing the efficiency of the subsequent InDEO by a 33%. In silico molecular docking analysis ascertained that cellulose fibers affect the InDEO process by interacting with the dyes that are responsible of the COD. On the other hand, P-InDEO resulted in both 95% of decolorization and 68% of COD removal, as a result of radical mediators. Free radicals generated during P-InDEO were characterized as oxychloride (OCl) by electron paramagnetic resonance spectroscopy (EPR). This form of coupled approach is especially suggested for the treatment of textile wastewater containing cellulose.

Enzymatic dehydrogenative polymerization of monolignol dimers

The structure and biosynthesis of lignin are not yet fully understood, especially the step following the initial dimerization of monolignol. Liquid chromatograph mass spectrometer (LC–MS) was used to analyze the consumption rates of monolignol dimers formed by β-O-4, β-5, and β-β couplings between coniferyl alcohols in efforts to understand the activity of monolignol dimers in enzymatic dehydrogenative polymerization. We investigated the reaction kinetics in single-component and mixed-component reaction systems containing one and two species of the dimers, respectively. A difference was observed between the consumption rates of the three dimers we tested, and the consumption rate of one dimer in the single-component reaction was different from that in a mixed-component reaction. In qualitative LC–MS analyses, coniferyl alcohol oligomers were detected in the reaction products. Some monolignol tetramers were formed by 5-5 and 5-O-4 coupling between the dimers. The results of this work suggested that monolignol dimers with β-5 and β-β linkages could function as radical mediators in enzyme-catalyzed polymerization.

Quantification of thiazolidine-4-carboxylic acid in toxicant-exposed cells by isotope-dilution liquid chromatography-mass spectrometry reveals an intrinsic antagonistic response to oxidative stress-induced toxicity.

Carcinogenic formaldehyde is produced by endogenous protein oxidation and various exogenous sources. With formaldehyde being both ubiquitous in the ambient environment and one of the most common reactive carbonyls produced from endogenous metabolism, quantifying formaldehyde exposure is an essential step in risk assessments. We present in this study an approach to assess the risk of exposure to oxidative stress by quantifying thiazolidine-4-carboxylic acid (TA), a cysteine-conjugated metabolite of formaldehyde in toxicant-exposed Escherichia coli. The method entails TA derivatization with ethyl chloroformate, addition of isotope-labeled TA derivatives as internal standards, solid-phase extraction of the derivatives, and quantification by liquid chromatography-mass spectrometry (LC-MS). After validating for accuracy and precision, the developed method was used to detect TA in oxidizing agent-exposed E. coli samples. Dose-dependent TA formation was observed in E. coli exposed to hydroxyl radical mediators Fe(2+)-EDTA, H2O2, and NaOCl, indicating the potential use of TA as a biomarker of exposure to oxidative stress and disease risk.

Selective cytotoxic action and DNA damage by calcitriol-Cu(II) interaction: putative mechanism of cancer prevention.

BackgroundVitamin D is known to play an important role in cancer-prevention. One of the features associated with the onset of malignancy is the elevation of Cu (II) levels. The mode of cancer-prevention mediated by calcitriol, the biologically active form of vitamin D, remain largely unknown.MethodsUsing exogenously added Cu (II) to stimulate a malignancy like condition in a novel cellular system of rabbit calcitriol overloaded lymphocytes, we assessed lipid peroxidation, protein carbonylation, DNA damage and consequent apoptosis. Free radical mediators were identified using free radical scavengers and the role of Cu (II) in the reaction was elucidated using chelators of redox active cellular metal ions.ResultsLipid peroxidation and protein carbonylation (markers of oxidative stress), consequent DNA fragmentation and apoptosis were observed due to calcitriol-Cu (II) interaction. Hydroxyl radicals, hydrogen peroxide and superoxide anions mediate oxidative stress produced during this interaction. Amongst cellular redox active metals, copper was found to be responsible for this reaction.ConclusionThis is the first report implicating Cu (II) and calcitriol interaction as the cause of selective cytotoxic action of calcitriol against malignant cells. We show that this interaction leads to the production of oxidative stress due to free radical production and consequent DNA fragmentation, which leads to apoptosis. A putative mechanism is presented to explain this biological effect.

ChemInform Abstract: Free Radical Mediated Hydroxymethylation Using CO and HCHO

AbstractReview: 36 refs.

Free Radical-mediated Hydroxymethylation Using CO and HCHO

Tin-free radical hydroxymethylations of haloalkanes using CO and HCHO as a C1 unit proceed efficiently in the presence of borohydrides as radical mediators. In the approach using CO, the formation of aldehydes by radical carbonylation and their subsequent reduction by hydrides lead to alcohols. On the other hand, the use of formaldehyde is more straightforward, in which the key reaction is alkyl radical addition to formaldehyde to give alkoxy radical, which abstracts hydrogen from borohydride reagents. The cascade sequences were observed in the reaction of cholesteryl bromide with HCHO, which displays the diverse applications of HCHO in radical chemistry.

The multiple challenges of obstructive sleep apnea in children: morbidity and treatment

To delineate some of the major morbid phenotypes that have emerged in pediatric obstructive sleep apnea (OSA), address new concepts in our understanding of OSA-associated morbidities, and elaborate on innovative therapeutic schemes that may improve outcomes for this condition. In addition, the conceptual framework whereby a childhood condition such as OSA can be linked to specific adult diseases will be presented. OSA in children is a frequent condition that affects up to 3% of nonobese, otherwise healthy children. In recent years, increased awareness of OSA and changes in obesity rates in children have contributed to significant changes in disease prevalence and clinical presentation, such that distinct morbidity-related phenotypes have become apparent. Furthermore, oxidative stress and systemic inflammatory pathways are mechanistically involved in the pathophysiology of OSA-associated morbidity. Adenotonsillectomy, the treatment of choice for pediatric OSA, may not be as efficacious as previously thought. Alternative nonsurgical therapies have started to emerge and may become an essential component of treatment. Pediatric OSA, particularly when obesity is concurrently present, is associated with substantial end-organ morbidities that primarily but not exclusively affect central nervous and cardiovascular systems. These morbidities are pathophysiologically mediated by inflammatory and free radical mediators. Although adenotonsillectomy remains the first line of treatment, more critical assessment of its role is needed, and incorporation of nonsurgical approaches to pediatric OSA seems warranted.

Synthetic Radical Reactions Using Dibutylchlorogermane and Dibutylethoxygermane as Radical Mediators.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Radical mediators and mitogen-activated protein kinase signaling in oxygen-dependent radiosensitivity of human tumor cell lines

Oxygen enhancement of tumor radiosensitivity is attributed to DNA damage by reactive oxygen species. The mechanism remains unclear but may involve mitochondria as major sources of oxygen and nitrogen radicals as well as central effectors of energy homeostasis and apoptosis. Here we used dihydrorhodamine and 2′,7′-dichlorodihydrofluorescein to compare mitochondrial and total cell generation, respectively, of reactive oxygen or nitrogen species in cells irradiated at 5 Gy. Irradiation in the presence of oxygen selectively stimulated mitochondrial radical production in HeLa and MeWo cells, but in MCF7 cells radical production was more generalized. In all three cell lines oxygen impaired cell proliferation as measured by resazurin reduction 7 days after irradiation. Antioxidants N-acetylcysteine, ascorbic acid, and melatonin largely prevented dye oxidation during normoxic irradiation yet had no effect on oxygen-dependent irradiation injury. However, NO synthase inhibitor N( G)-monomethyl- l-arginine protected HeLa and MCF7 though not MeWo cells, consistent with their different levels of constitutive NO generation. SB203580 inhibition of p38 MAPK appreciably protected HeLa and marginally protected MCF7 cells against oxygen-dependent irradiation injury, while the less specific JNK/SAPK inhibitor SP600125 and ERK inhibitor U0126 had no effect. None of the inhibitors affected MeWo radiosensitivity. Therefore oxygen-enhanced radiosensitivity in these tumor cell lines does not depend on extensive production of oxygen radicals and is cell-type dependent. NO mediates oxygen-dependent injury in HeLa and MCF7 cells, by p38-dependent and MAPK–independent mechanisms, respectively. In MeWo cells this oxygen-enhanced radiosensitivity is independent of both NO and MAPK signaling.

Synthetic Radical Reactions Using Dibutylchlorogermane and ­Dibutylethoxygermane as Radical Mediators

In the presence of Et 3 B as radical initiator, dibutylchlorogermane (1a) and dibutylethoxygermane (lb) reacted with bromo- and iodoalkanes at room temperature to give the corresponding aikanes in high yields. Hydrogermanela was more reactive than 1b. However, lb worked as a better radical mediator in intermolecular radical addition of haloalkanes to electron-deficient alkenes.

Hydrogen bonding between histidine and lignin model compounds or redox mediators as calculated with the DFT method. Effects on the ease of oxidation.

Using the Density Functional Theory method, the effect of hydrogen bonding between imidazole (IM) and ten benzyl alcohol derivatives (BA) on the ionization potentials of the latter is calculated. IM is used as a model for histidine, which is found in the reaction sites of laccases and lignin peroxidases, and the BA-derivatives serve as lignin model compounds. A marked decrease ([similar]15 kcal mol(-1)) is found for the IP's of the BA-derivatives when paired with IM. This should facilitate the one-electron oxidation of BA in the reaction site of the enzyme. The same effect is found for the known redox mediators violuric acid, 1-hydroxybenzotriazole and N-hydroxyacetanilide which are assumed to enter the reaction site of the enzymes. Furthermore, upon one-electron oxidation the strength of the H-bond from BA to IM is considerably increased and in the case of the mediators this effect is so pronounced that the relevant proton shifts from them to IM. If this occurs in the active site of the enzyme then the oxidized redox mediators are released into the aqueous phase in their neutral form rather than as radical cations (deprotonation of the radical cations). The oxidation power of the neutral radical mediators, however, is too low to initialize oxidation of lignin. A more likely reaction pathway is oxidation of the substrates via hydrogen abstraction. The pertinent bond dissociation energies are similar for the BA-derivatives and the redox mediators, which in principle allows the reaction to occur.

Enhanced activity by poly(ethylene glycol) modification of Coriolopsis gallica laccase.

We are studying the enzymatic modification of polycyclic aromatic hydrocarbons (PAHs) by the laccase from Coriolopsis gallica UAMH 8260. The enzyme was produced during growth in a stirred tank reactor to 15 units ml(-1), among the highest levels described for a wild-type fungus; the enzyme was the major protein produced under these conditions. After purification, it exhibited characteristics typical of a white rot fungal laccase. Fifteen azo and phenolic compounds at 1 mM concentration were tested as mediators in the laccase oxidation of anthracene. Higher anthracene oxidation was obtained with the mediator combination of ABTS and HBT, showing a correlation between the oxidation rate and the mediator concentration. Reactions with substituted phenols and anilines, conventional laccase substrates, and PAHs were compared using the native laccase and enzyme preparations chemically modified with 5000 MW-poly(ethylene glycol). Chemically modified laccase oxidized a similar range of substituted phenols as the native enzyme but with a higher catalytic efficiency. The k(cat) increase by the chemical modification may be as great as 1300 times for syringaldazine oxidation. No effect was found of chemical modification on mediated PAH oxidation. Both unmodified and PEG-modified laccases increased PAH oxidation up to 1000 times in the presence of radical mediators. Thus, a change of the protein surface improves the mediator oxidation efficiency, but does not affect non-enzymatic PAH oxidation by oxidized mediators.

Oxidation of carbazole, N-ethylcarbazole, fluorene, and dibenzothiophene by the laccase of Coriolopsis gallica

Purified laccase from Coriolopsis gallica UAMH8260 oxidized carbazole, N-ethylcarbazole, fluorene, and dibenzothiophene in the presence of 1-hydroxybenzotriazole and 2,2′-azinobis (3-ethylbenzthiazoline-6-sulfonic acid) as free radical mediators. Susceptibility to laccase oxidation appears related to the ionization potential (IP) of the substrate: compounds with an IP above 8.52, dibenzofuran (IP = 8.77) and benzothiophene (IP = 8.73) were not attacked. Carbazole (IP = 7.68) was the most sensitive to oxidation with >99% transformed with 10 milliunits of laccase after 1 h, though most reactions were carried out for 18 h. 9-Fluorenone was identified as the product of fluorene (IP = 8.52) oxidation, and dibenzothiophene sulfone from dibenzothiophene (IP = 8.44). Although carbazole and N-ethylcarbazole were both completely removed within 18 h, no oxidation or condensation metabolites were detected. This investigation is the first to report the oxidation of dibenzothiophene, carbazole, and N-ethylcarbazole by laccase.