Oxygen Transfer Agent Research Articles

The mechanism and origins of the chemo- and regio-selectivity of ruthenium porphyrin catalyzed C[sbnd]H bonds oxidation

Selective functionalization of polymers derived from branched alkane monomers is extremely challenging due to the low reactivity of CH bonds and uncontrolled depolymerization. In this work, the chemoselective and regioselective catalytic oxygenation mechanism of hydrocarbons with ruthenium porphyrin complexes and aromatic N-oxides was investigated by density functional theory (DFT) calculations. The results revealed that the oxoruthenium porphyrin species with remarkable reactivity as oxygen transfer agents is responsible for the hydrogen abstraction from CH bonds followed by fast hydroxyl radical rebound. Details regarding the calculations of various oxidation processes show that the regioselectivity is related to the intrinsic strength of different CH bonds in branched alkanes and the charge transfer of the hydrogen atom transfer (HAT) step. Comparing the oxidations of branched alkanes to alcohols and ketones, the chemoselectivity is attributed to the relative barriers of HAT pathways in the two-step oxidation stage. Finally, the substituent effects of fluorine in the porphyrin ligand are elucidated and a stronger electron-withdrawing group is predicted to promote the HAT process and regulate hydroxyl radical rebound, ultimately enabling more efficient oxidation. These findings provide relevant information for understanding the selective oxidation of polyolefins through transition metal catalysis and enzymatic catalysis.

Untangling the catalytic importance of the Se oxidation state in organoselenium-mediated oxygen-transfer reactions: the conversion of aniline to nitrobenzene.

Seleninic acids and their precursors are well-known oxygen-transfer agents that can catalyze several oxidations with H2O2 as the final oxidant. Until very recently, the Se(iv) "peroxyseleninic" acid species has been considered the only plausible catalytic oxidant. Conversely, in 2020, the involvement of Se(vi) "peroxyselenonic" acid has been proposed for the selenium mediated epoxidation of alkenes. In this work, we theoretically probe different mechanisms of H2O2 activation and of Se(iv) to Se(vi) interconversion. In addition, we investigate through a combined theoretical (DFT) and experimental approach the mechanistic steps leading to the oxidation of aniline to nitrobenzene, when Se(iv) seleninic acid or Se(vi) selenonic acids are used as catalysts and H2O2 as the oxidant. This process encompasses three subsequent organoselenium mediated oxidations by H2O2. These results provide a mechanistic explanation of the advantages and disadvantages of both oxidation states (iv and vi) in the different stages of catalytic oxygen-transfer reactions: hydrogen peroxide activation and actual substrate oxidation. While the Se(vi) "peroxyselenonic" acid is found to be a better oxidant, the privileged role of "peroxyseleninic" acid as the main active species is assessed and its origin is identified in the lower catalyst-distortion that seleninic acid undergoes when activating H2O2. Conversely, the higher catalyst-distortion that characterizes the reaction of selenonic acid with H2O2 supports an inactivating role of Se(iv) to Se(vi) interconversion.

Photocatalytic Oxygen Transfer as an Innovative Route for N2O Upgrading**

AbstractAs concentration of nitrous oxide (N2O) keeps growing steeply in the atmosphere, upgrading this anthropogenic greenhouse gas as a potential oxygen transfer agent constitutes a real challenge to limit global warming and ozone layer depletion. Decomposition of N2O is mainly described under highly energy‐consuming thermal activation, owing to its high stability and large activation barrier, making it kinetically inert. Herein, we demonstrate the controlled photocatalytic upgrading of N2O as an oxygen atom donor, releasing only dinitrogen (N2) as a benign co‐product. The doped Ag@TiO2 photocatalyst specifically activates N2O for controlled oxidation of phosphines avoiding mineralization, under mild conditions (room temperature, 1 atm, λ=365 nm), as a proof‐of‐concept of the valorization of N2O as an oxygen transfer agent. The catalytic system is active and selective in various organic solvents, as well as innovatively in water, depending on the phosphine structure.

Ni-Catalyzed Oxygen Transfer from N2O onto sp3-Hybridized Carbons.

Herein we disclose a catalytic synthesis of cycloalkanols that harnesses the potential of N2O as an oxygen transfer agent onto sp3-hybridized carbons. The protocol is distinguished by its mild conditions and wide substrate scope, thus offering an opportunity to access carbocyclic compounds from simple precursors even in an enantioselective manner. Preliminary mechanistic studies suggest that the oxygen insertion event occurs at an alkylnickel species and that N2O is the O transfer reagent.

Solar-driven chemical looping reforming of methane over SrFeO3-δ-Ca0.5Mn0.5O nanocomposite foam

Strontium ferrite (SrFeO3-δ) is a very attractive oxygen transfer agent for chemical looping reactions and hydrogen-rich syngas generation. Dispersing SrFeO3 in a medium such as Ca0.5Mn0.5O could enhance the activity and cyclability. In this study, SrFeO3-δ-Ca0.5Mn0.5O (30 wt% SrFeO3-δ) nanocomposite with a reticulated foam structure was explored as the oxygen carrier for chemical looping reforming of methane in a solar tubular reactor. The foam nanocomposite was prepared by a hard-templating method. The performance was investigated at temperatures of 850–1000 °C and methane flowrates of 25–250 STP mL/min, and the oxidative gas was either CO2 or H2O in the oxidation step. In the reduction step of 27 successive redox cycles, the production rate of CO changed marginally and CO yield maintained at about 1.9 mmol/g, even though sintering occurred. The productivity of H2 decreased first and then tended to be stable at 3.8 mmol/g (i.e., twice the CO yield) as the cycling number increased (the average oxygen storage capacity of the material was ∼1.95 mmol/g). Microscopic and X-ray diffraction investigations suggested that the element distribution pattern and crystalline phase of the foam nanocomposite remained almost unchanged after 27 redox cycles, confirming material stability. The maximum solar-to-fuel efficiency for the foam nanocomposite was 5.68%, which was 21.4% higher than that for the powder nanocomposite. To increase syngas productivity and solar-to-fuel efficiency, it is required to conduct the reforming reaction at high temperatures and methane flowrates. However, the energy upgrade factor will decrease as methane flowrate increases.

Orthogonal Preparation of SrFeO3-δ Nanocomposites as Effective Oxygen Transfer Agents for Chemical-Looping Steam Methane Reforming

Orthogonal Preparation of SrFeO_3-δ Nanocomposites as Effective Oxygen Transfer Agents for Chemical-Looping Steam Methane Reforming

Essentials for Combined Experimental and Computational 77Se NMR of Organoselenium Catalysts and Bioinspired Antioxidants

The importance of selenium in biology, in organic catalysis, and green chemistry is well established. Selenoproteins, among which are ubiquitous Glutathione Peroxidases (GPx), play a key role in mitigating oxidative stress by reducing H2O2 and hydroperoxides using glutathione as a cofactor. Organoselenides, particularly diphenyl diselenide, in the presence of H2O2, are efficient and often green oxygen transfer agents in important organic reactions, such as Baeyer-Villiger oxidations of ketones/aldehydes, the conversion of alkenes into epoxides, and the oxidations of alcohols and nitrogen- containing compounds. NMR spectroscopy can facilitate the investigation of the properties of this element in a biological environment and the characterization of the peculiar species of its chemistry. In this short review, a brief overview of the experimental and computational 77Se NMR-based techniques is outlined, with a particular focus on their applications to the study of biologically relevant organoselenium compounds and bio-mimetic systems. Experimental protocols, together with computational methods used in different contexts, are presented and their potential as efficient investigation tools is critically discussed. It emerges that while the 77Se NMR measurement is a consolidated technique, no standard computational protocol is available to compute the shielding constant of the chalcogen nucleus with accuracy and the optimal approach combines molecular dynamics in solution and quantum chemistry calculations to take into account the conformational freedom.

Oxidation of 1-propanol to propionic acid with hydrogen peroxide catalysed by heteropolyoxometalates

BackgroundPropionic acid as a very valuable chemical is in high demand, and it is industrially produced via the oxo-synthesis of ethylene or ethyl alcohol and via the oxidation of propionaldehyde with oxygen. It is urgent to discover a new preparation method for propionic acid via a green route. Recyclable amino-acid-based organic–inorganic heteropolyoxometalates were first used to high-efficiently catalyse the selective oxidation of 1-propanol to propionic acid with H2O2 as an oxidant.ResultA series of amino-acid-based heteropoly catalysts using different types of amino acids and heteropoly acids were synthesized, and the experimental results showed proline-based heteropolyphosphatotungstate (ProH)3[PW12O40] exhibited excellent catalytic activity for the selective catalytic oxidation of 1-propanol to propionic acid owing to its high capacity as an oxygen transfer agent and suitable acidity. Under optimized reaction conditions, the conversion of 1-propanol and the selectivity of propionic acid reached 88% and 75%, respectively. Over four cycles, the conversion remained at >80%, and the selectivity was >60%. (ProH)3[PW12O40] was also used to catalyse the oxidations of 1-butanol, 1-pentanol, 1-hexanol, and benzyl alcohol. All the reactions had high conversions, with the corresponding acids being the primary oxidation product.ConclusionsProline-based heteropolyoxometalate (ProH)3[PW12O40] has been successfully used to catalyse the selective oxidation of primary alcohols to the corresponding carboxylic acids with H2O2 as the oxidant. The new developed catalytic oxidation system is mild, high-efficient, and reliable. This study provides a potential green route for the preparation propionic acid.

Chlorine-promoted perovskite nanocomposite as a high-performance oxygen transfer agent for chemical looping methane-assisted CO2 splitting

Metal oxide-mediated CO2 splitting with the assistance of methane (aka chemical looping dry reforming of methane) is a novel and attractive approach for CO2 utilization. Herein, we demonstrate that doping and tailoring the redox window of strontium ferrite (SrFeO3-δ)-calcium oxide nanocomposites are effective strategies to improve the performance of chemical looping reforming. The oxygen storage capacity of this redox material is about 0.82 mol O/kg. Chlorine promotes coking in the reduction step; the tailored window not only suppresses complete oxidation of methane but also enhances CO2 transformation in a fixed-bed reactor. At 980 °C, the carbon efficiency is as high as 99%, very close to the equilibrium value. In this case, no recycling or downstream separation is needed, making the proposed scheme more efficient. In addition, both the yield of CO and the productivity of syngas remain stable over 10 redox cycles. This exceptional redox performance makes the chloride-promoted SrFeO3-δ-based nanocomposites a highly competitive and cost-effective chemical looping material.

CO2-free conversion of CH4 to syngas using chemical looping

Chemical looping can provide attractive alternative process routes in which solid oxygen carriers function as lattice oxygen transfer agents, for example for the partial oxidation of methane. We report on the development of a perovskite-based oxygen carrier (La0.85Sr0.15Fe0.95Al0.05O3-δ) that enables the complete conversion of CH4 to a synthesis gas (a mixture of H2 and CO, selectivity > 99 %) through donation of its lattice oxygen (up to 9 wt%) at temperatures > 900 °C. The thermodynamic properties of the oxygen carrier permit its lattice oxygen to be replenished with CO2 or H2O, of which > 94 % is converted into CO or H2, respectively. The potential of this compositionally and structurally flexible oxygen carrier is demonstrated in a continuous experiment lasting more than 45 days (∼ 4050 redox cycles), in which all CH4 (reductant) and all CO2 (oxidant) is converted into a synthesis gas without CO2 contamination.

Continued Progress towards Efficient Functionalization of Natural and Non-natural Targets under Mild Conditions: Oxygenation by C-H Bond Activation with Dioxirane.

The successful isolation and characterization of a dioxirane species in 1988 opened up one of the most attractive methods for the efficient oxidation of simple and/or structurally complex molecules. Dioxirane today rank among the most powerful tools in organic chemistry, with numerous applications in commercially important processes. They were quickly recognized as efficient oxygen transfer agents, especially for epoxidations and for a wide range of O-insertion reactions into C-H bonds. Dioxirane possess catalytic activity and appear as highly (chemo-, regio-, and stereo-) selective oxidants, despite their reactivity under mild and strictly neutral conditions being controlled by a combination of steric and electronic factors. In this review, we discuss some of the most recent and significant developments in the selective homogeneous and heterogeneous oxyfunctionalization of non-activated C-H bonds in hydrocarbons of natural and non-natural targets by using isolated dioxirane or, more generally, by using the ketones (i.e., the dioxirane precursors) as organocatalysts.

Coproduction of Hydrogen and Methanol from Methane by Chemical Looping Reforming

Coproduction of hydrogen and methanol from methane by chemical looping reforming is a novel approach to transform natural gas. Compared with conventional reforming processes, the mole ratio of methane to water fed to a chemical looping reactor can be the stoichiometric ratio without concerns over coking. In this work, the redox scheme was experimentally and numerically investigated, where a SrFeO3−δ perovskite acted as the oxygen transfer agent. To improve its redox performance, SrFeO3−δ was dispersed into three oxides: CaO, MnO, and CaO·MnO. Among them, CaO·MnO enhances the reforming performance best. Specifically, SrFeO3−δ/CaO·MnO composites exhibit 6.9% coke selectivity, 66.2% maximum instantaneous methane conversion, and 91.5% syngas (H2/CO ≈ 2) selectivity in the methane partial oxidation step and up to 90% H2O to H2 conversion in the water splitting step at a redox temperature of 900 °C. Further studies suggest that the low coke selectivity stems from the reaction between manganese oxide and coke or its precursor, which becomes more favorable at high temperatures. To evaluate the process of solar fuel production by chemical looping technology, an economic analysis of the coproduction of the hydrogen and methanol process was carried out and compared with conventional methanol synthesis. Compared with thermally driven methanol synthesis, the solar-driven coproduction scheme demonstrates 14% exergy efficiency improvement, 63% CO2 emission reduction, and 1.9 times more net income than the former. Our findings demonstrate that solar-driven chemical looping reforming is a very promising option for solar fuel production.

Preparation of Dielectric Films via Thermal Oxidation of MnO2/GaAs

MnO2 nanolayers (~29 nm) produced on the surface of single-crystal GaAs wafers by magnetron sputtering have been shown to act as oxygen transfer agents for the thermal oxidation of the semiconductor. The presence of MnO2 increases the oxide film growth rate by three to nine times relative to stimulator-free oxidation of GaAs. The films thus grown range in thickness from 35 to 200 nm and possess good dielectric properties (resistivity on the order of ~1010 Ω cm and dielectric strength in the range (5–8) × 106 V/cm). According to X-ray diffraction data, the films are enriched in oxidized arsenic and have a regular grain structure in the surface layer, with a roughness height within 30 nm (according to atomic force microscopy data).

Pegylated Bovine Carboxyhemoglobin (SANGUINATE) in a Jehovah's Witness Undergoing Liver Transplant: A Case Report

Liver transplantation in practicing Jehovah's Witnesses is challenging because of their religious beliefs preventing them from accepting allogenic blood products. Pegylated bovine carboxyhemoglobin (SANGUINATE) is an oxygen transfer agent, currently under investigation for the treatment of sickle cell disease, which may play a role in these patients by maximizing perioperative oxygen delivery. We report a case involving the use of SANGUINATE in a Jehovah's Witness undergoing liver transplant.

SANGUINATE™ (PEGylated Carboxyhemoglobin Bovine) Improves Cerebral Blood Flow to Vulnerable Brain Regions at Risk of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been linked to focal reductions in cerebral blood flow (CBF) and microvascular impairments in oxygen delivery. Effective therapies that restore flow and oxygen transport to vulnerable brain regions are currently lacking. SANGUINATE is a dual-action carbon monoxide-releasing and hemoglobin-based oxygen transfer agent with efficacy in animal models of focal brain ischemia and tolerability in patients with sickle cell disease. We performed a safety and proof-of-principle study in 12 SAH patients at risk of DCI across three escalating doses (160, 240, and 320mg/kg). We used 15O-PET (performed at baseline, after SANGUINATE and at 24h) to evaluate efficacy for improving CBF and restoring flow-metabolism balance (assessed by oxygen extraction fraction [OEF]) to vulnerable regions (defined as baseline OEF≥0.50). SANGUINATE resulted in a transient rise in mean arterial pressure (116±15-127±13mm Hg, p=0.001) that normalized by 24h and allowed three patients with DCI to be weaned off vasopressors. No adverse events were noted during infusion. Global CBF did not rise (43±8-46±9ml/100g/min) although a trend was seen at the highest dose (45±7-51±9, p=0.044). However, a significant 16% rise in regional CBF associated with reduction in OEF was seen in vulnerable regions, but did not persist at 24h. We demonstrated that this novel agent can improve regional CBF and may improve oxygen supply-demand balance. Clinical studies (likely with repeat dosing) are required to evaluate whether this effect can prevent DCI or cerebral infarction.

Abstract 196: Sanguinate (PEGylated-carboxyhemoglobin-bovine) Improves Cerebral Blood Flow and Oxygen Extraction to Vulnerable Brain Regions in Patients at Risk for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Introduction: Sanguinate is a dual-action oxygen transfer and carbon monoxide-releasing agent with efficacy in animal models of focal brain ischemia and established safety in health volunteers. We performed a dose-escalation study in subarachnoid hemorrhage (SAH) patients at risk for delayed cerebral ischemia (DCI) to evaluate tolerability and explore efficacy in improving cerebral blood flow (CBF) and flow-metabolism balance to vulnerable brain regions. Methods: 12 subjects were studied over three dose tiers: 160mg/kg, 240 mg/kg, and 320 mg/kg, with close safety evaluation prior to proceeding to higher doses. After baseline 15 O-PET measurement of global and regional CBF and oxygen extraction fraction (OEF), Sanguinate was infused over two hours; PET was repeated immediately after and again at 24-hours. Vulnerable brain regions were defined as those with baseline OEF ≥ 0.5. Results: Sanguinate infusion resulted in a significant but transient rise in mean arterial pressure (115±15 to 127±13 mm Hg) that was not dose-dependent. No adverse physiologic or clinical effects were observed with infusion at any dose. Global CBF did not rise significantly after Sanguinate (42.6±7 to 45.9±9 ml/100g/min, p=0.18). However, in the 28% of regions classified as vulnerable, Sanguinate resulted in a significant rise in CBF (42.2±11 to 51.2±18) and reduction in OEF (0.6±0.1 to 0.5±0.11, both p<0.001). The increase in regional CBF was only seen with the two higher doses but OEF improved in all tiers. However, response was attenuated at 24-hours. Conclusions: We safely administered a novel oxygen transport and vasodilating agent to a cohort of patients with SAH. Sanguinate infusion appeared to improve CBF and flow-metabolism balance in vulnerable brain regions and warrants further study in those at-risk for DCI. Higher or repeat dosing may be required for sustained efficacy.

A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia.

BackgroundTreatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities.MethodsAn open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160 mg/kg) of SANGUINATE or 15 mg/kg hydroxyurea. Another 12 subjects received either a high dose (320 mg/kg) of SANGUINATE or 15 mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements.ResultsMusculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients.ConclusionsThe clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials.

Nonstoichiometry in Strontium Uranium Oxide: Understanding the Rhombohedral-Orthorhombic Transition in SrUO4.

In situ neutron and synchrotron X-ray diffraction studies demonstrate that SrUO4 acts as an oxygen transfer agent, forming oxygen vacancies under both oxidizing and reducing conditions. Two polymorphs of SrUO4 are stable at room temperature, and the transformation between these is observed to be associated with thermally regulated diffusion of oxygen ions, with partial reduction of the U(6+) playing a role in both the formation of oxygen deficient α-SrUO4-δ and its subsequent transformation to stoichiometric β-SrUO4. This is supported by ab initio calculations using density functional theory calculations. The oxygen vacancies play a critical role in the first order transition that SrUO4 undergoes near 830 °C. The changes in the oxidation states and U geometry associated with the structural phase transition have been characterized using X-ray absorption spectroscopy, synchrotron X-ray diffraction, and neutron diffraction.

PEGylated Bovine Carboxyhemoglobin (SANGUINATE™): Results of Clinical Safety Testing and Use in Patients.

Oxygen transfer agents have long been sought as a means to treat hypoxia caused by congenital or acquired conditions. Hemoglobin-based oxygen carriers were in clinical development as blood substitutes, but development was halted due to the finding of significant vasoactivity. Rather than develop a blood substitute, a product for indications characterized by hypoxia is in development. PEGylated bovine carboxyhemoglobin (SANGUINATE™) is both a carbon monoxide releasing molecule and an oxygen transfer agent. It is comprised of three functional components that act to inhibit vasoconstriction, reduce inflammation and optimize the delivery of oxygen. SANGUINATE has the potential to reduce or prevent the effects of ischemia by inhibiting vasoconstriction and re-oxygenating tissue. Phase 1 safety trials in healthy volunteers were completed in 2013. SANGUINATE was shown to be safe and well tolerated with no serious adverse effects. Phase Ib studies have been completed in stable patients with Sickle Cell Disease. SANGUINATE has also been administered to two patients under emergency use protocols. Both patients exhibited improved status following treatment with SANGUINATE.

Developments in Synthetic Application of Selenium(IV) Oxide and Organoselenium Compounds as Oxygen Donors and Oxygen-Transfer Agents.

A variety of selenium compounds were proven to be useful reagents and catalysts for organic synthesis over the past several decades. The most interesting aspect, which emerged in recent years, concerns application of hydroperoxide/selenium(IV) oxide and hydroperoxide/organoselenium catalyst systems, as “green reagents” for the oxidation of different organic functional groups. The topic of oxidations catalyzed by organoselenium derivatives has rapidly expanded in the last fifteen years This paper is devoted to the synthetic applications of the oxidation reactions mediated by selenium compounds such as selenium(IV) oxide, areneseleninic acids, their anhydrides, selenides, diselenides, benzisoselenazol-3(2H)-ones and other less often used other organoselenium compounds. All these compounds have been successfully applied for various oxidations useful in practical organic syntheses such as epoxidation, 1,2-dihydroxylation, and α-oxyfunctionalization of alkenes, as well as for ring contraction of cycloalkanones, conversion of halomethyl, hydroxymethyl or active methylene groups into formyl groups, oxidation of carbonyl compounds into carboxylic acids and/or lactones, sulfides into sulfoxides, and secondary amines into nitrones and regeneration of parent carbonyl compounds from their azomethine derivatives. Other reactions such as dehydrogenation and aromatization, active carbon-carbon bond cleavage, oxidative amidation, bromolactonization and oxidation of bromide for subsequent reactions with alkenes are also successfully mediated by selenium (IV) oxide or organoselenium compounds. The oxidation mechanisms of ionic or free radical character depending on the substrate and oxidant are discussed. Coverage of the literature up to early 2015 is provided. Links have been made to reviews that summarize earlier literature and to the methods of preparation of organoselenium reagents and catalysts.