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Ecotoxicology and Environmental Safety Jul 2022Chromium (Cr) is mainly found in the form of organic-Cr(III) complexes in the natural environment and industrial waste. The widespread existence of composite... (Review)
Review
Chromium (Cr) is mainly found in the form of organic-Cr(III) complexes in the natural environment and industrial waste. The widespread existence of composite contaminants composed of organic matter (OM) and Cr pose a serious ecological threat, and its potential interaction and removal need to be further summarised. Organic ligands, such as carbohydrates, nitrogen compounds, phenolic compounds, humus substances (HS), and low molecular weight organic acids (LMWOAs), play an important role in governing the speciation, mobility, and absorption and desorption of Cr in the environment. Moreover, growing evidence indicates that oxygen-containing functional groups (e.g., carboxyl, hydroxyl, and phosphate) are closely related to the complexation of Cr(III). Advanced oxidation processes (AOPs) are efficient and widely applicable technologies. However, the re-complexation of oxidation intermediates with Cr(III) and the formation and accumulation of much more toxic Cr(VI) species hinder the possible utilisation of AOPs. In this paper, the sources and harmful effects of organic-Cr(III) complexes are reported in detail. The complexation behaviour and structure of the organic-Cr(III) complexes are also described. Subsequently, the application of AOPs in the decomplexation and degradation of organic-Cr(III) complexes is summarised. This review can be helpful for developing technologies that are more efficient for organic-Cr(III) complex removal and establishing the scientific background for reducing Cr discharge Cr into the environment.
Topics: Chromium; Hydroxyl Radical; Industrial Waste; Organic Chemicals; Oxidation-Reduction
PubMed: 35653974
DOI: 10.1016/j.ecoenv.2022.113676 -
The Journal of Steroid Biochemistry and... Oct 2023Lumisterol (L2) is a photoproduct of UVB action on the fungal membrane sterol, ergosterol. Like vitamin D, it is present in edible mushrooms, especially after UV...
Lumisterol (L2) is a photoproduct of UVB action on the fungal membrane sterol, ergosterol. Like vitamin D, it is present in edible mushrooms, especially after UV irradiation. Lumisterol is similarly produced in human skin from 7-dehydrocholesterol by UVB and can be converted to hydroxy-metabolites by CYP27A1 and CYP11A1. These products are biologically active on human cells with actions that include photoprotection and inhibition of proliferation. The aim of this study was to test the ability of CYP11A1 and CYP27A1 to metabolise L2. Purified CYP27A1 was found to efficiently metabolise L2 to three major products and several minor products, whilst CYP11A1 did not act appreciably on L2. The three major products of CYP27A1 action on L2 were identified by mass spectrometry and NMR as 24-hydroxyL2, 27-hydroxyL2 and 28-hydroxyL2. Minor products included two dihydroxy L2 species, one which was identified as 24,27(OH)L2, and another metabolite with one oxo and one hydroxyl group added. A comparison on the kinetics of the metabolism of L2 by CYP27A1 with that of the structurally similar compounds, L3 and ergosterol, was carried out with substrates incorporated into phospholipid vesicles. CYP27A1 displayed a 12-fold lower K with L2 as substrate compared to L3 and a 5-fold lower turnover number (k), resulting in a 2.2 fold higher catalytic efficiency (k/K) for L2 metabolism. L2 was a much better substrate for CYP27A1 than its precursor, ergosterol, with a catalytic efficiency 18-fold higher. The major CYP27A1-derived hydroxy-L2 products, 24-hydroxyL2, 27-hydroxyL2 and 28-hydroxyL2, inhibited the proliferation of melanoma and epidermoid cancer cell lines. In conclusion, this study shows that L2 is not metabolized appreciably by CYP11A1, but it is a good substrate for CYP27A1 which hydroxylates its side chain to produce 3 major products that display anti-proliferative activity on skin-cancer cell lines.
Topics: Humans; Ergosterol; Cholesterol Side-Chain Cleavage Enzyme; Hydroxylation; Mass Spectrometry; Ergocalciferols; Cholestanetriol 26-Monooxygenase
PubMed: 37499840
DOI: 10.1016/j.jsbmb.2023.106370 -
Cell Death & Disease Jul 2022Notch signaling plays a pivotal role in the development and, when dysregulated, it contributes to tumorigenesis. The amplitude and duration of the Notch response depend...
Notch signaling plays a pivotal role in the development and, when dysregulated, it contributes to tumorigenesis. The amplitude and duration of the Notch response depend on the posttranslational modifications (PTMs) of the activated NOTCH receptor - the NOTCH intracellular domain (NICD). In normoxic conditions, the hydroxylase FIH (factor inhibiting HIF) catalyzes the hydroxylation of two asparagine residues of the NICD. Here, we investigate how Notch-dependent gene transcription is regulated by hypoxia in progenitor T cells. We show that the majority of Notch target genes are downregulated upon hypoxia. Using a hydroxyl-specific NOTCH1 antibody we demonstrate that FIH-mediated NICD1 hydroxylation is reduced upon hypoxia or treatment with the hydroxylase inhibitor dimethyloxalylglycine (DMOG). We find that a hydroxylation-resistant NICD1 mutant is functionally impaired and more ubiquitinated. Interestingly, we also observe that the NICD1-deubiquitinating enzyme USP10 is downregulated upon hypoxia. Moreover, the interaction between the hydroxylation-defective NICD1 mutant and USP10 is significantly reduced compared to the NICD1 wild-type counterpart. Together, our data suggest that FIH hydroxylates NICD1 in normoxic conditions, leading to the recruitment of USP10 and subsequent NICD1 deubiquitination and stabilization. In hypoxia, this regulatory loop is disrupted, causing a dampened Notch response.
Topics: Cell Hypoxia; Humans; Hydroxylation; Mixed Function Oxygenases; Receptor, Notch1; Signal Transduction; T-Lymphocytes; Ubiquitin Thiolesterase
PubMed: 35821235
DOI: 10.1038/s41419-022-05052-9 -
ChemMedChem Jun 2022C-H oxyfunctionalisation remains a distinct challenge for synthetic organic chemists. Oxygenases and peroxygenases (grouped here as "oxygenating biocatalysts") catalyse... (Review)
Review
C-H oxyfunctionalisation remains a distinct challenge for synthetic organic chemists. Oxygenases and peroxygenases (grouped here as "oxygenating biocatalysts") catalyse the oxidation of a substrate with molecular oxygen or hydrogen peroxide as oxidant. The application of oxygenating biocatalysts in organic synthesis has dramatically increased over the last decade, producing complex compounds with potential uses in the pharmaceutical industry. This review will focus on hydroxyl functionalisation using oxygenating biocatalysts as a tool for drug discovery and development. Established oxygenating biocatalysts, such as cytochrome P450s and flavin-dependent monooxygenases, have widely been adopted for this purpose, but can suffer from low activity, instability or limited substrate scope. Therefore, emerging oxygenating biocatalysts which offer an alternative will also be covered, as well as considering the ways in which these hydroxylation biotransformations can be applied in drug discovery and development, such as late-stage functionalisation (LSF) and in biocatalytic cascades.
Topics: Biocatalysis; Cytochrome P-450 Enzyme System; Drug Discovery; Hydroxylation; Oxidation-Reduction
PubMed: 35385205
DOI: 10.1002/cmdc.202200115 -
Applied Microbiology and Biotechnology Aug 2020Amino groups derived from naturally abundant amino acids or (di)amines can be used as "shuttles" in nature for oxygen transfer to provide intermediates or products... (Review)
Review
Amino groups derived from naturally abundant amino acids or (di)amines can be used as "shuttles" in nature for oxygen transfer to provide intermediates or products comprising N-O functional groups such as N-hydroxy, oxazine, isoxazolidine, nitro, nitrone, oxime, C-, S-, or N-nitroso, and azoxy units. To this end, molecular oxygen is activated by flavin, heme, or metal cofactor-containing enzymes and transferred to initially obtain N-hydroxy compounds, which can be further functionalized. In this review, we focus on flavin-dependent N-hydroxylating enzymes, which play a major role in the production of secondary metabolites, such as siderophores or antimicrobial agents. Flavoprotein monooxygenases of higher organisms (among others, in humans) can interact with nitrogen-bearing secondary metabolites or are relevant with respect to detoxification metabolism and are thus of importance to understand potential medical applications. Many enzymes that catalyze N-hydroxylation reactions have specific substrate scopes and others are rather relaxed. The subsequent conversion towards various N-O or N-N comprising molecules is also described. Overall, flavin-dependent N-hydroxylating enzymes can accept amines, diamines, amino acids, amino sugars, and amino aromatic compounds and thus provide access to versatile families of compounds containing the N-O motif. Natural roles as well as synthetic applications are highlighted. Key points • N-O and N-N comprising natural and (semi)synthetic products are highlighted. • Flavin-based NMOs with respect to mechanism, structure, and phylogeny are reviewed. • Applications in natural product formation and synthetic approaches are provided. Graphical abstract .
Topics: Bacteria; Biocatalysis; Biological Products; Flavins; Flavoproteins; Humans; Hydroxylation; Kinetics; Mixed Function Oxygenases; Oxygen; Secondary Metabolism; Siderophores
PubMed: 32504128
DOI: 10.1007/s00253-020-10705-w -
Food and Chemical Toxicology : An... Oct 2018The formation of o-quinones from direct 2-electron oxidation of catechols and/or two successive one electron oxidations could explain the cytotoxic/genotoxic and/or... (Review)
Review
The formation of o-quinones from direct 2-electron oxidation of catechols and/or two successive one electron oxidations could explain the cytotoxic/genotoxic and/or chemopreventive effects of several phenolic botanical extracts. For example, poison ivy contains urushiol, an oily mixture, which is oxidized to various o-quinones likely resulting in skin toxicity through oxidative stress and alkylation mechanisms resulting in immune responses. Green tea contains catechins which are directly oxidized to o-quinones by various oxidative enzymes. Alternatively, phenolic botanicals could be o-hydroxylated by P450 to form catechols in vivo which are oxidized to o-quinones. Examples include, resveratrol which is oxidized to piceatannol and further oxidized to the o-quinone. Finally, botanical o-quinones can be formed by O-dealkylation of O-alkoxy groups or methylenedioxy rings resulting in catechols which are further oxidized to o-quinones. Examples include safrole, eugenol, podophyllotoxin and etoposide, as well as methysticin. Once formed these o-quinones have a variety of biological targets in vivo resulting in various biological effects ranging from chemoprevention -> no effect -> toxicity. This U-shaped biological effect curve has been described for a number of reactive intermediates including o-quinones. The current review summarizes the latest data on the formation and biological targets of botanical o-quinones.
Topics: Activation, Metabolic; Alkylation; DNA; Glutathione; Hydroxylation; Oxidation-Reduction; Plants; Proteins; Quinones
PubMed: 30063944
DOI: 10.1016/j.fct.2018.07.050 -
International Journal of Molecular... Apr 2018Ion channels activated by reactive oxygen species (ROS) have been found in the plasma membrane of charophyte , dicotyledon , and , and the monocotyledon . Their... (Review)
Review
Ion channels activated by reactive oxygen species (ROS) have been found in the plasma membrane of charophyte , dicotyledon , and , and the monocotyledon . Their activities have been reported in charophyte giant internodes, root trichoblasts and atrichoblasts, pollen tubes, and guard cells. Hydrogen peroxide and hydroxyl radicals are major activating species for these channels. Plant ROS-activated ion channels include inwardly-rectifying, outwardly-rectifying, and voltage-independent groups. The inwardly-rectifying ROS-activated ion channels mediate Ca-influx for growth and development in roots and pollen tubes. The outwardly-rectifying group facilitates K⁺ efflux for the regulation of osmotic pressure in guard cells, induction of programmed cell death, and autophagy in roots. The voltage-independent group mediates both Ca influx and K⁺ efflux. Most studies suggest that ROS-activated channels are non-selective cation channels. Single-channel studies revealed activation of 14.5-pS Ca influx and 16-pS K⁺ efflux unitary conductances in response to ROS. The molecular nature of ROS-activated Ca influx channels remains poorly understood, although annexins and cyclic nucleotide-gated channels have been proposed for this role. The ROS-activated K⁺ channels have recently been identified as products of Stellar K⁺ Outward Rectifier () and Guard cell Outwardly Rectifying K⁺ channel () genes.
Topics: Animals; Calcium Signaling; Humans; Hydroxyl Radical; Plants; Potassium; Reactive Oxygen Species
PubMed: 29690632
DOI: 10.3390/ijms19041263 -
Organic & Biomolecular Chemistry May 2019Discussed herein is the synthesis of partially protected carbohydrates by manipulating only one type of a protecting group for a given substrate. The first focus of this... (Review)
Review
Discussed herein is the synthesis of partially protected carbohydrates by manipulating only one type of a protecting group for a given substrate. The first focus of this review is the uniform protection of an unprotected starting material in a way that only one (or two) hydroxyl group remains unprotected. The second focus involves regioselective partial deprotection of uniformly protected compounds in a way that only one (or two) hydroxyl group becomes liberated.
Topics: Carbohydrate Conformation; Carbohydrates; Hydroxyl Radical; Stereoisomerism
PubMed: 31044205
DOI: 10.1039/c9ob00573k -
Environmental Science & Technology Sep 2022The photolysis of pesticides with different fluorine motifs was evaluated to quantify the formation of fluorinated products in buffered aqueous systems, advanced...
The photolysis of pesticides with different fluorine motifs was evaluated to quantify the formation of fluorinated products in buffered aqueous systems, advanced oxidation (AOP) and reduction processes (ARP), and river water. Simulated sunlight quantum yields at pH 7 were 0.0033, 0.0025, 0.0015, and 0.00012 for penoxsulam, florasulam, sulfoxaflor, and fluroxypyr, respectively. The bimolecular rate constants with hydroxyl radicals were 2 to 5.7 × 10 M s and, with sulfate radicals, 1.6 to 2.6 × 10 M s for penoxsulam, florasulam, and fluroxypyr, respectively. The rate constants of sulfoxaflor were 100-fold lower. Using quantitative F-NMR, complete fluorine mass balances were obtained. The maximum fluoride formation was 53.4 and 87.4% for penoxsulam and florasulam under ARP conditions, and 6.1 and 100% for sulfoxaflor and fluroxypyr under AOP conditions. Heteroaromatic CF and aliphatic CF groups were retained in multiple fluorinated photoproducts. Aryl F and heteroaromatic F groups were readily defluorinated to fluoride. CF and CF groups formed trifluoroacetate and difluoroacetate, and yields increased under oxidizing conditions. F-NMR chemical shifts and coupling analysis provided information on hydrogen loss on adjacent bonds or changes in chirality. Mass spectrometry results were consistent with the observed F-NMR products. These results will assist in selecting treatment processes for specific fluorine motifs and in the design of agrochemicals to reduce byproduct formation.
Topics: Fluorides; Fluorine; Hydroxyl Radical; Pesticides; Photolysis
PubMed: 35972505
DOI: 10.1021/acs.est.2c04242 -
Journal of the American Chemical Society Oct 2018The atomistic change of C( sp)-H to C( sp)-O can have a profound impact on the physical and biological properties of small molecules. Traditionally, chemical synthesis... (Review)
Review
The atomistic change of C( sp)-H to C( sp)-O can have a profound impact on the physical and biological properties of small molecules. Traditionally, chemical synthesis has relied on pre-existing functionality to install new functionality, and directed approaches to C-H oxidation are an extension of this logic. The impact of developing undirected C-H oxidation reactions with controlled site-selectivity is that scientists gain the ability to diversify complex structures at sites remote from existing functionality, without having to carry out individual de novo syntheses. This Perspective offers a historical view of why, as recently as 2007, it was thought that the differences between aliphatic C-H bonds of the same bond type (for example, 2° aliphatic) were not large enough to distinguish them preparatively with small-molecule catalysis in the absence of directing groups or molecular recognition elements. We give an account of the discovery of Fe(PDP)-catalyzed non-directed aliphatic C-H hydroxylations and how the electronic, steric, and stereoelectronic rules for predicting site-selectivity that emerged have affected a shift in how the chemical community views the reactivity among these bonds. The discovery that site-selectivity could be altered by tuning the catalyst [i.e., Fe(CF-PDP)] with no changes to the substrate or reaction now gives scientists the ability to exert control on the site of oxidation on a range of functionally and topologically diverse compounds. Collectively, these findings have made possible the emerging area of late-stage C-H functionalizations for streamlining synthesis and derivatizing complex molecules.
Topics: Catalysis; Ferrous Compounds; Hydroxylation; Molecular Structure; Oxidation-Reduction; Small Molecule Libraries
PubMed: 30185033
DOI: 10.1021/jacs.8b05195