Oxidative Degradation Pathways Research Articles

Remote Amino Acid Recognition Enables Effective Hydrogen Peroxide Activation at a Manganese Oxidation Catalyst

AbstractPrecise delivery of a proton plays a key role in O2 activation at iron oxygenases, enabling the crucial O−O cleavage step that generates the oxidizing high‐valent metal–oxo species. Such a proton is delivered by acidic residues that may either directly bind the iron center or lie in its second coordination sphere. Herein, a supramolecular strategy for enzyme‐like H2O2 activation at a biologically inspired manganese catalyst, with a nearly stoichiometric amount (1–1.5 equiv) of a carboxylic acid is disclosed. Key for this strategy is the incorporation of an α,ω‐amino acid in the second coordination sphere of a chiral catalyst via remote ammonium‐crown ether recognition. The properly positioned carboxylic acid function enables effective activation of hydrogen peroxide, leading to catalytic asymmetric epoxidation. Modulation of both amino acid and catalyst structure can tune the efficiency and the enantioselectivity of the reaction, and a study on the oxidative degradation pathway of the system is presented.

Peroxide activation by microbially synthesized sulfidated iron: Comparison against abiotic iron-based materials in terms of treatment efficiency and oxidative degradation pathway

This study demonstrated the application of biogenic sulfidated iron (B-FeS), produced via anaerobic digestion of Desulfovibrio desulfuricans using sulfate as the terminal electron acceptor, for peroxide activation. B-FeS was assessed against chemically prepared zerovalent and sulfidated iron (ferrous sulfide and pyrite) with respect to their ability to activate peroxydisulfate (PDS) and H2O2. Regardless of the peroxide type, B-FeS outperformed benchmark iron activators in treating 4-chlorophenol due to its resistance to iron corrosion and the high content of reduced sulfur. The roles of oxidizing radicals were confirmed based on the effects of alcohol-based quenchers, multi-activity assessment, electron paramagnetic resonance spectral features, and product analysis. The pH-dependent efficiency of sulfoxide-to-sulfone conversion suggested that high-valent iron species acted as the secondary oxidant in all iron/peroxide systems, and the contribution was more pronounced when PDS and B-FeS were used. Microbial sulfidation as a catalyst regeneration strategy recovered the peroxide activation capacity of oxidized B-FeS.

Potential Degradation of 4‐Methyltetrahydropyran (4‐MeTHP) under Oxidation Conditions

Abstract4‐Methyltetrahydropyran (4‐MeTHP) is a next‐generation recyclable ether solvent that can be applied to a wide variety of synthetic reaction methods. Previous studies indicated that 4‐MeTHP could degrade to some extent with certain oxidants, while the oxidation reactions themselves proceeded in good yields. Here we disclose the potential oxidative degradation pathways of 4‐MeTHP when exposed to selected organic‐based and metal‐based oxidants. Crude NMR analyses revealed that degradation of 4‐MeTHP was initiated by C2−H abstraction, giving rise to C2‐ or C4‐oxidized products or the C−C bond cleavage product depending on the oxidants used. This study therefore illustrates possible degradation products of 4‐MeTHP under oxidative conditions, which is particularly helpful in predicting and analyzing trace impurities when adopting 4‐MeTHP or other ethereal solvents in industrial processes.

Characterization of Polysorbate 80 by Liquid Chromatography-Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway

A liquid chromatography-mass spectrometry (LC–MS) method was developed to provide a fingerprint of polysorbate 80 (PS80) subspecies that enables identification of PS80 degradation pathway. The developed method demonstrates unique monoester peak profile of PS80 from different vendors, attributed by differences in relative abundance of the fatty acid monoesters.The LC–MS method was also applied to examine the susceptibility of PS80, at different grades, to auto-oxidation and hydrolysis. PS80 oxidative degradation induced by iron or occurred in open bottle without nitrogen overlay was found to follow the same pathway, but at a much faster rate in the former scenario. The oxidation preferentially occurs at the double bond of fatty acid chains, thus providing explanation on the faster degradation observed in PS80 at Chinese Pharmacopia (ChP) grade than at multi-compendial (MC) grade. In contrast, the difference in susceptibility of MC and ChP grade PS80 against esterase-induced hydrolysis in placebo was not pronounced. The method was also able to provide a fingerprint to identify both PS80 hydrolysis and oxidation in mAb drug product stability samples, but it required a solid phase extraction step to remove protein prior to the analysis.

Systematic Review of Serum Biomarkers in Traumatic Brain Injury.

Traumatic brain injury (TBI) is responsible for the majority of trauma-related deaths and is a leading cause of disability. It is characterized by an inflammatory process involved in the progression of secondary brain injury. TBI is measured by the Glasgow Coma Scale (GCS) with scores ranging from 15-3, demonstrating mild to severe brain injury. Apart from this clinical assessment of TBI, compendiums of literature have been published on TBI-related serum markers.Herein we create a comprehensive appraisal of the most prominent serum biomarkers used in the assessment and care of TBI.The PubMed, Scopus, Cochrane, and Web of Science databases were queried with the terms “biomarker” and “traumatic brain injury” as search terms with only full-text, English articles within the past 10 years selected. Non-human studies were excluded, and only adult patients fell within the purview of this analysis. A total of 528 articles were analyzed in the initial search with 289 selected for screening. A further 152 were excluded for primary screening. Of the remaining 137, 54 were included in the final analysis. Serum biomarkers were listed into the following broad categories for ease of discussion: immune markers and markers of inflammation, hormones as biomarkers, coagulation and vasculature, genetic polymorphisms, antioxidants and oxidative stress, apoptosis and degradation pathways, and protein markers. Glial fibrillary acidic protein(GFAP), S100, and neurons specific enolase (NSE) were the most prominent and frequently cited markers. Amongst these three, no single serum biomarker demonstrated neither superior sensitivity nor specificity compared to the other two, therefore noninvasive panels should incorporate these three serum biomarkers to retain sensitivity and maximize specificity for TBI.

Mycoremediation of an agricultural salty soil contaminated with endosulfan by Penicillium crustosum: and agronomic bioassays with Phaseolus leptostachyus

The fungus Penicillium crustosum was employed for endosulfan biodegradation, finding that sulphate endosulfan and mono alcohol endosulfan were the main compounds produced; therefore, an oxidative degradation pathway was suggested. A 93 ± 4.7% of Endosulfan degradation after one month of treatment of a highly salty agricultural soil was obtained, where ΔST was up to 17 ± 0.58 mN m−1, (related to the water value of 72 mNm−1), that was induced by the fungus during soil mycoremediation Additionally, an improvement in soil quality (reduction of clay proportion and salinity, as well as an increase of soluble phosphorus, carbon content and organic matter) was observed during the mycoremediation treatment. The phytotoxicity of the pesticide on Phaseolus leptostachyus was evaluated in the soil without the fungus addition (control), where the pesticide was translocated in the crop, presenting a negative effect in germination index, root length and weight, aerial weight, humidity, and proline content. This contrasted with the effect on the crop grown in the soil treated with P. crustosum, which had better agronomic characteristics. This is first report in which the effect of this property allows the pesticide biodegradation, due to a combined Endosulfan bioavailability and fungal biodegradation.

Comprehensive insight into the chlorophyll degradation mechanism of postharvest broccoli heads under elevated O2 controlled atmosphere

Postharvest broccoli heads undergo yellowing quickly in unsuitable conditions, which diminishes their quality and commercial value. We investigated the pattern and molecular regulatory mechanism of chlorophyll (Chl) degradation in broccoli under elevated O2 controlled atmosphere. As results, the 40% O2 + 5% CO2 treatment accelerated the Chl degradation and the change in color of postharvest broccoli heads, while the 5% O2 + 5% CO2 treatment delayed the yellowing. The results indicated that Chl degradation pattern of postharvest broccoli heads concurrently involved the Pheide a oxygenase (PAO)/phyllobilin and oxidative degradation pathways, and the latter might be the dominant pathway of Chl degradation. The regulatory mechanism of elevated O2 on Chl degradation may be related to its ability to accelerate cell damage and death, destroy the light-harvesting complex II, and promote up-regulation of genes in the PAO/phyllobilin and oxidative degradation pathways. In contrast, low O2 treatment may down-regulate the expression of Chl degradation-related genes by increasing H2O2 content, thus delaying the yellowing of broccoli heads.

ID-MAM: A Validated Identity and Multi-Attribute Monitoring Method for Commercial Release and Stability Testing of a Bispecific Antibody.

Post-translational modifications (PTMs) that impact the safety or efficacy of protein therapeutics are critical quality attributes (CQAs) that need to be controlled to ensure product quality. Peptide mapping with online mass spectrometry (MS) is a powerful tool that has been used for many years to monitor PTM CQAs during product development. However, operating peptide mapping methods with high-resolution mass spectrometers in GMP compliant, commercial quality control (QC) labs can be difficult. Peptide mapping is also required as an identity test in several countries. To address these two different needs, we utilized high-resolution peptide mapping for comprehensive characterization during development and then developed and validated a targeted multi-attribute monitoring (MAM) method using the low-resolution Waters QDa MS system with a fully automated data processing workflow that is suitable for identity (ID) testing, sequence variant control, and CQA quantitation in commercial QC labs. The ID-MAM method was validated for the quantitation of three selected PTM CQAs (CDR isomerization, Fc Met oxidation, and CDR Met oxidation) to ensure control of the oxidation and isomerization degradation pathways of a bispecific antibody (BsAb). This ID-MAM method was successfully validated in six labs (three analytical development and three QC labs) across four countries for commercial release and stability testing of a BsAb. CQA results obtained with the ID-MAM method were similar to results obtained using high-resolution peptide mapping, and the method was robust and reproducible. To our knowledge, this ID-MAM method is the first MS-based peptide mapping method implemented in GMP compliant QC labs for commercial release and stability testing of a biotherapeutic.

Enhanced removal of oxytetracycline antibiotics from water using manganese dioxide impregnated hydrogel composite: Adsorption behavior and oxidative degradation pathways

The present work provides the first attempt of using manganese dioxide loaded poly(sodium acrylate) hydrogel (MnO2@PSA) to address potential threats posed by oxytetracycline (OTC) antibiotics in aqueous environment. The MnO2@PSA was prepared via a facile approach and demonstrated enhanced removal performance even under extremely high concentrations of OTC. The outstanding performance exhibited by MnO2@PSA was attributed to synergetic effects of adsorption oxidative degradation. The synthesized composite was characterized evaluated under varying conditions. The adsorption pH was optimized at pH 5, at which the removal efficiency OTC was reached 91.46%. According to the kinetics study, the pseudo-second-order kinetic model was the best to explain the adsorption data, implying the interaction mechanisms were dominated by chemisorption. The Langmuir isotherm model was the best to explain the isotherm data, and the corresponding maximum adsorbed amount of OTC was 1150.4 mg g−1. The MnO2@PSA was highly selective for OTC adsorption and degradation under the presence of natural organic matter and common environmental metal ions. The oxidative degradation study indicated that OTC molecules were structurally degraded into 15 intermediate products via six reaction pathways. Both the theoretical models and spectroscopic methods demonstrated the removal mechanism of OTC onto MnO2@PSA was governed by ion exchange, cation-π bonding, hydrogen-bonding, and π-π electron donor-acceptor. Overall, MnO2@PSA is an excellent and environmentally sustainable material to remove OTC from water and wastewater via the combined effects of adsorption and oxidative degradation.

Integration of Proteomics and Metabolomics Into the Design, Build, Test, Learn Cycle to Improve 3-Hydroxypropionic Acid Production in Aspergillus pseudoterreus.

Biological engineering of microorganisms to produce value-added chemicals is a promising route to sustainable manufacturing. However, overproduction of metabolic intermediates at high titer, rate, and yield from inexpensive substrates is challenging in non-model systems where limited information is available regarding metabolic flux and its control in production conditions. Integrated multi-omic analyses of engineered strains offers an in-depth look at metabolites and proteins directly involved in growth and production of target and non-target bioproducts. Here we applied multi-omic analyses to overproduction of the polymer precursor 3-hydroxypropionic acid (3HP) in the filamentous fungus Aspergillus pseudoterreus. A synthetic pathway consisting of aspartate decarboxylase, beta-alanine pyruvate transaminase, and 3HP dehydrogenase was designed and built for A. pseudoterreus. Strains with single- and multi-copy integration events were isolated and multi-omics analysis consisting of intracellular and extracellular metabolomics and targeted and global proteomics was used to interrogate the strains in shake-flask and bioreactor conditions. Production of a variety of co-products (organic acids and glycerol) and oxidative degradation of 3HP were identified as metabolic pathways competing with 3HP production. Intracellular accumulation of nitrogen as 2,4-diaminobutanoate was identified as an off-target nitrogen sink that may also limit flux through the engineered 3HP pathway. Elimination of the high-expression oxidative 3HP degradation pathway by deletion of a putative malonate semialdehyde dehydrogenase improved the yield of 3HP by 3.4 × after 10 days in shake-flask culture. This is the first report of 3HP production in a filamentous fungus amenable to industrial scale biomanufacturing of organic acids at high titer and low pH.

Insights into flibanserin oxidative stress degradation pathway: in silico – in vitro toxicity assessment of its degradates

Characterization of the degradation products of pharmaceutical drugs is essential to assess their safety.

First total synthesis of 3a-hydroxy-1,1-dimethyl-5-((N-methylsulfamoyl)methyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-1-ium 2,2,2-trifluoroacetate by mimicking the oxidative degradation pathway of sumatriptan

The expiry date of any medicine is decided based on the time span during which the drug product maintains its quality and is safe as well as effective. The levels of various impurities present in any drug product are considered safe based on various toxicological studies in preclinical species and safety parameters monitoring during clinical studies. The shelf life of US FDA approved sumatriptan auto-injector product ZEMBRACE SymTouch was extended till 36 months after toxicological qualification of the degradation compound 3a-hydroxy-1,1-dimethyl-5-((N-methylsulfamoyl)methyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-1-ium 2,2,2-trifluoroacetate. The first total synthesis of this degradation product by mimicking the oxidative degradation pathway of sumatriptan is described herein. © 2021 Elsevier Science. All rights reserved.

Electrochemical advanced oxidation processes for wastewater treatment: Advances in formation and detection of reactive species and mechanisms

Abstract Over the past three decades, the knowledge of the mechanisms of electrochemical advanced oxidation processes (EAOPs) has progressively evolved with the advances in analytical and spectrometric techniques. A comprehensive understanding of the types and mechanisms of production of reactive species in EAOPs is a prerequisite to the understanding of their reactivities and elucidation of intermediate products generated during the oxidation process and degradation pathways. The type, nature, and quantity of reactive species generated in electrochemical treatment processes are controlled by many factors, including the type of the treatment technique, electrode/electrocatalyst materials, water/wastewater composition, water pH conditions, and operating parameters. Depending on the technique and operating parameters, single or multiple oxidants can be produced alone or combined electrochemical processes. However, the potency and reactivity of each oxidant are quite similar regardless of the technique, except in the case of heterogeneous and homogeneous hydroxyl radicals. This minireview presents the current state of mechanisms and models of reactive species generated in different EAOPs, highlighting different methods for their identification and reactivity.

Investigation of the Oxidative Degradation Pathway of Amidoximes by LC/MS/MS

The oxidative degradation pathway for a newly prepared amidoxime prodrug has been studied using LC/MS/MS. The amidoxime was subjected to oxidation with K3Fe(CN)6/NaOH for different time periods and at different temperatures. The chromatographic separation was performed on RP amide column and 0.1% aqueous formic acid; acetonitrile containing 0.1% formic acid (50:50 v/v) as a mobile phase. The elution in Ultra-performance liquid chromatography (UPLC) was carried out in the isocratic mode. The normal LC/MS/MS showed that the cleavage occurs through amidoxime ester. At room temperature, no important oxidation products were obtained. However, upon heating the parent amidoxime was disappeared with the concomitant appearance of a new compound which is the most stable peak (base peak) at m/z = 333.80. The formed degradation product was suggested to be the disodium salt of benzaldoxime peroxide. These results give indication about the mechanism of release of nitric oxide from amidoxime and ensure that amidoximes are important nitric oxide donors.

Representing Organic Matter Thermodynamics in Biogeochemical Reactions via Substrate-Explicit Modeling.

Predictive biogeochemical modeling requires data-model integration that enables explicit representation of the sophisticated roles of microbial processes that transform substrates. Data from high-resolution organic matter (OM) characterization are increasingly available and can serve as a critical resource for this purpose, but their incorporation into biogeochemical models is often prohibited due to an over-simplified description of reaction networks. To fill this gap, we proposed a new concept of biogeochemical modeling—termed substrate-explicit modeling—that enables parameterizing OM-specific oxidative degradation pathways and reaction rates based on the thermodynamic properties of OM pools. Based on previous developments in the literature, we characterized the resulting kinetic models by only two parameters regardless of the complexity of OM profiles, which can greatly facilitate the integration with reactive transport models for ecosystem simulations by alleviating the difficulty in parameter identification. The two parameters include maximal growth rate (μmax) and harvest volume (Vh) (i.e., the volume that a microbe can access for harvesting energy). For every detected organic molecule in a given sample, our approach provides a systematic way to formulate reaction kinetics from chemical formula, which enables the evaluation of the impact of OM character on biogeochemical processes across conditions. In a case study of two sites with distinct OM thermodynamics using ultra high-resolution metabolomics datasets derived from Fourier transform ion cyclotron resonance mass spectrometry analyses, our method predicted how oxidative degradation is primarily driven by thermodynamic efficiency of OM consistent with experimental rate measurements (as shown by correlation coefficients of up to 0.61), and how biogeochemical reactions can vary in response to carbon and/or oxygen limitations. Lastly, we showed that incorporation of enzymatic regulations into substrate-explicit models is critical for more reasonable predictions. This result led us to present integrative biogeochemical modeling as a unifying framework that can ideally describe the dynamic interplay among microbes, enzymes, and substrates to address advanced questions and hypotheses in future studies. Altogether, the new modeling concept we propose in this work provides a foundational platform for unprecedented predictions of biogeochemical and ecosystem dynamics through enhanced integration with diverse experimental data and extant modeling approaches.

Transcriptomic Analysis of Two Lentinula edodes Genotypes With Different Cadmium Accumulation Ability.

Lentinula edodes, also known as Xiang’gu, is commonly eaten in cultures around the world. However, L. edodes is particularly susceptible to enrichment with heavy metals, particularly cadmium (Cd), which is toxic to human health. Understanding the molecular mechanism and mining key genes involved in Cd enrichment will facilitate genetic modification of L. edodes strains. Two L. edodes genotypes, Le4625 (with higher Cd enrichment capability) and Le4606 (with lower Cd enrichment capability) were used in this study. The Cd concentrations in the mycelia of the tested genotypes differed significantly after Cd (0.1 mg/L) exposure; and the Cd content in Le4625 (1.390 ± 0.098 mg/kg) was approximately three-fold that in Le4606 (0.440 ± 0.038 mg/kg) after 7 h of Cd exposure. A total of 24,592 transcripts were assessed by RNA-Seq to explore variance in Cd accumulation. Firstly, differentially expressed genes (DEGs) were analyzed separately following Cd exposure. In comparison with Ld4625, Ld4606 showed a greater number of Cd-induced changes in transcription. In Ld4606, DEGs following Cd exposure were associated with transmembrane transport, glutathione transfer and cytochrome P450, indicating that these genes could be involved in Cd resistance in L. edodes. Next, Le4606 and Le4625 were exposed to Cd, after which DEGs were identified to explore genetic factors affecting Cd accumulation. After Cd exposure, DEGs between Le4606 and Le4625 encoded proteins involved in multiple biological pathways, including transporters on the membrane, cell wall modification, oxidative stress response, translation, degradation, and signaling pathways. Cadmium enrichment in cells may activate MAPK signaling and the anti-oxidative stress response, which can subsequently alter signal transduction and the intracellular oxidation/reduction balance. Furthermore, several possible candidate genes involved in the Cd accumulation were identified, including the major facilitator superfamily genes, heat shock proteins, and laccase 11, a multicopper oxidase. This comparison of the transcriptomes of two L. edodes strains with different capacities for Cd accumulation provides valuable insight into the cultivation of mushrooms with less Cd enrichment and also serves as a reference for the construction of engineered strains for environmental pollution control.

Base-Mediated Oxidative Degradation of Secondary Amides Derived from p-Amino Phenol to Primary Amides in Drug Molecules

One of the most common functional groups encountered in drug molecules is the amide, and the most common degradation pathway for amides is base-mediated hydrolysis to its constituent amine and carboxylic acid. Herein, we report for the first time, a base-mediated oxidative degradation pathway of secondary amides to primary amides. This transformation also represents a novel synthetic methodology, reported for the first time in this work, in transforming secondary amides to primary amides without using any oxidative reagents. The introduction of this mechanism into the pharmaceutical literature is important given that the mechanism and required reactants are present to carry out the chemistry in dosage forms.

Degradation of carbamazepine by MWCNTs-promoted generation of high-valent iron-oxo species in a mild system with O-bridged iron perfluorophthalocyanine dimers

Metal phthalocyanine has been extensively studied as a catalyst for degradation of carbamazepine (CBZ). However, metal phthalocyanine tends to undergo their own dimerization or polymerization, thereby reducing their activity points and affecting their catalytic properties. In this study, a catalytic system consisting of O-bridged iron perfluorophthalocyanine dimers (FePcF16-O-FePcF16), multi-walled carbon nanotubes (MWCNTs) and H2O2 was proposed. The results showed MWCNTs loaded with FePcF16-O-FePcF16 can achieve excellent degradation of CBZ with smaller dosages of FePcF16-O-FePcF16 and H2O2, and milder reaction temperatures. In addition, the results of experiments revealed the reaction mechanism of non-hydroxyl radicals. The highly oxidized high-valent iron-oxo (Fe(IV)=O) species was the main reactive species in the FePcF16-O-FePcF16/MWCNTs/H2O2 system. It is noteworthy that MWCNTs can improve the dispersion of FePcF16-O-FePcF16, contributing to the production of highly oxidized Fe(IV)=O. Then, the pathway of CBZ oxidative degradation was speculated, and the study results also provide new ideas for metal phthalocyanine-loaded carbon materials to degrade emerging pollutants.

Current Knowledge on the Function of α-Methyl Acyl-CoA Racemase in Human Diseases.

Branched chain fatty acids perform very important functions in human diet and drug metabolism. they cannot be metabolized in mitochondria and are instead processed and degraded in peroxisomes due to the presence of methyl groups on the carbon chains. Oxidative degradation pathways for lipids include α- and β-oxidation and several pathways. In all metabolic pathways, α-methyl acyl-CoA racemase (AMACR) plays an essential role by regulating the metabolism of lipids and drugs. AMACR regulates β-oxidation of branched chain lipids in peroxisomes and mitochondria and promotes chiral reversal of 2-methyl acids. AMACR defects cause sensory-motor neuronal and liver abnormalities in humans. These phenotypes are inherited and are caused by mutations in AMACR. In addition, AMACR has been found to be overexpressed in prostate cancer. In addition, the protein levels of AMACR have increased significantly in many types of cancer. Therefore, AMACR may be an important marker in tumors. In this review, a comprehensive overview of AMACR studies in human disease will be described.

Simulation of the environmental degradation of diuron (herbicide) using electrochemistry coupled to high resolution mass spectrometry

The environmental degradation of contaminants such as pesticides can hinder the ability of analytical instruments, even high-performance system such as mass spectrometry, to detect and quantify contamination reliably. There is thus a need for developing synthetic approaches that allow the fast identification of contaminants markers that can be later support quantitative analysis. Combining electrochemical cell (EC), liquid chromatography (LC) and electrospray mass spectrometry (MS) (online EC-MS and offline EC-LC-MS) allows the rapid identification of some oxidation products of diuron (DIU) in the absence and in the presence of glutathione. The structural elucidation of DIU oxidation products was based on retention time, m/z ratio in positive mode and fragmentation pattern. Reactions such as hydrolytic dechlorination, hydroxylation, dehydrochlorination, dehydrogenation/hydrogenation, conjugation and dimerization have been successfully mimicked serving applications such as drug metabolism and environmental degradation simulation. The resort to electrochemistry to simulate naturally occurring reaction has been of particular interest for the production of reactive intermediate species. In this study, quinone imines, highly electrophilic chemical intermediates, have been identified as transformation products during the oxidative metabolism of diuron for the first time. The obtained results, supported by theoretical calculations, are useful for predicting and understanding the oxidative DIU degradation pathway.