-
Proceedings of the National Academy of... Dec 2023Natural products that possess antibiotic and antitumor qualities are often suspected of working through oxidative mechanisms. In this study, two quinone-based small...
Natural products that possess antibiotic and antitumor qualities are often suspected of working through oxidative mechanisms. In this study, two quinone-based small molecules were compared. Menadione, a classic redox-cycling compound, was confirmed to generate high levels of reactive oxygen species inside . It inactivated iron-cofactored enzymes and blocked growth. However, despite the substantial levels of oxidants that it produced, it was unable to generate significant DNA damage and was not lethal. Streptonigrin, in contrast, was poorer at redox cycling and did not inactivate enzymes or block growth; however, even in low doses, it damaged DNA and killed cells. Its activity required iron and oxygen, and in vitro experiments indicated that its quinone moiety transferred electrons through the adjacent iron atom to oxygen. Additionally, in vitro experiments revealed that streptonigrin was able to damage DNA without inhibition by catalase, indicating that hydrogen peroxide was not involved. We infer that streptonigrin can reduce bound oxygen directly to a ferryl species, which then oxidizes the adjacent DNA, without release of superoxide or hydrogen peroxide intermediates. This scheme allows streptonigrin to kill a bacterial cell without interference by scavenging enzymes. Moreover, its minimal redox-cycling behavior avoids alerting either the OxyR or the SoxRS systems, which otherwise would block killing. This example highlights qualities that may be important in the design of oxidative drugs. These results also cast doubt on proposals that bacteria can be killed by stressors that merely stimulate intracellular O and HO formation.
Topics: Oxidants; Hydrogen Peroxide; Anti-Bacterial Agents; Streptonigrin; Oxidative Stress; Escherichia coli; Oxygen; Iron; DNA; Quinones
PubMed: 38109539
DOI: 10.1073/pnas.2312110120 -
Free Radical Biology & Medicine 1997Peroxynitrite oxidizes D,L-selenomethionine (MetSe) by two competing mechanisms, a one-electron oxidation that leads to ethylene and a two-electron oxidation that gives...
Peroxynitrite oxidizes D,L-selenomethionine (MetSe) by two competing mechanisms, a one-electron oxidation that leads to ethylene and a two-electron oxidation that gives methionine selenoxide (MetSeO). Kinetic modeling of the experimental data suggests that both peroxynitrous acid and the peroxynitrite anion react with MetSe to form MetSeO with rate constants of 20,460 +/- 440 M-1 s-1 and 200 +/- 170 M-1 s-1, respectively at 25 degrees C. The enthalpy (delta H++) and entropy (delta S++) of activation for the reaction of peroxynitrous acid with MetSe at pH 4.6 are 2.55 +/- 0.08 kcal mol-1 and -30.5 +/- 0.3 cal mol-1 K-1, respectively. With increasing concentrations of MetSe at pH 7.4, the yield of ethylene decreases and that of MetSeO increases, suggesting, as with methionine, the reactions leading to ethylene and MetSeO have different kinetic orders. We propose that the activated form of peroxynitrous acid, HOONO*, is the one-electron oxidant and ground-state peroxynitrite is the two-electron oxidant in the reaction of peroxynitrite with MetSe. The peroxynitrite anion rapidly adds to CO2 to form an adduct, O = N-OO-CO2- (1), capable of generating potent reactive species, and we therefore examined the role of CO2 in the peroxynitrite/MetSe system. In presence of added bicarbonate, the yield of ethylene obtained from the reaction of 0.4 mM peroxynitrite with 1.0 mM MetSe increases slightly with an increase in the concentration of bicarbonate from 0 to 5.0 mM and remains constant with a further increase of bicarbonate up to 20 mM. The yield of MetSeO, from the reaction of 10 mM peroxynitrite with 10 mM MetSe, decreases by 35% with an increase in the concentration of bicarbonate from 0 to 25 mM. Kinetic simulations show that the decrease in the yield of MetSeO is due to reaction of the peroxynitrite anion with CO2. These results suggest that CO2 partially protects MetSe from peroxynitrite-mediated oxidation and that 1 or its derivatives do not mediate the oxidation of MetSe to MetSeO.
Topics: Carbon Dioxide; Ethylenes; Hydrogen-Ion Concentration; Kinetics; Nitrates; Organoselenium Compounds; Oxidants; Oxidation-Reduction; Selenomethionine; Temperature
PubMed: 9378371
DOI: 10.1016/s0891-5849(97)00099-3 -
Free Radical Biology & Medicine Sep 2008Exposure of cells to sublethal oxidative stress results in the modulation of various signaling pathways. Oxidants can activate and inactivate transcription factors,... (Review)
Review
Exposure of cells to sublethal oxidative stress results in the modulation of various signaling pathways. Oxidants can activate and inactivate transcription factors, membrane channels, and metabolic enzymes, and regulate calcium-dependent and phosphorylation signaling pathways. Oxidation and reduction of thiol proteins are thought to be the major mechanisms by which reactive oxidants integrate into cellular signal transduction pathways. This review focuses on mechanisms for sensing and transmitting redox signals, from the perspective of their chemical reactivity with specific oxidants. We discuss substrate preferences for different oxidants and how the kinetics of these reactions determines how each oxidant will react in a cell. This kinetic approach helps to identify initial oxidant-sensitive targets and elucidate mechanisms involved in transmission of redox signals. It indicates that only those proteins with very high reactivity, such as peroxiredoxins, are likely to be direct targets for hydrogen peroxide. Other more modestly reactive thiol proteins such as protein tyrosine phosphatases are more likely to become oxidized by an indirect mechanism. The review also examines oxidative changes observed during receptor-mediated signaling, the strengths and limitations of detection methods for reactive oxidant production, and the evidence for hydrogen peroxide acting as the second messenger. We discuss areas where observations in cell systems can be rationalized with the reactivity of specific oxidants and where further work is needed to understand the mechanisms involved.
Topics: Animals; Humans; Models, Biological; Oxidants; Oxidation-Reduction; Reactive Oxygen Species; Signal Transduction; Substrate Specificity; Sulfhydryl Compounds
PubMed: 18544350
DOI: 10.1016/j.freeradbiomed.2008.05.004 -
Water Research Mar 2002In the present study the treatment efficiency of different AOPs (O3/OH- H2O2/UV-C and TiO2/UV-A) were compared for the oxidation of simulated reactive dyebath effluent... (Comparative Study)
Comparative Study
In the present study the treatment efficiency of different AOPs (O3/OH- H2O2/UV-C and TiO2/UV-A) were compared for the oxidation of simulated reactive dyebath effluent containing a mixture of monochlorotriazine type reactive dyes and various dye auxiliary chemicals at typical concentrations encountered in exhausted reactive dyebath liquors. A525 (color), UV280 (aromaticity) and TOC removal rates were assessed to screen the most appropriate oxidative process in terms of reactive dyebath effluent treatment. Special emphasis was laid on the effect of reaction pH and applied oxidant (O3, H2O2) dose on the observed reaction kinetics. It was established that the investigated AOPs were negatively affected by the Na2CO3 content (= 867 mg/L) which is always present at high concentrations in dychouse effluents since it is applied as a pH buffer and dye fixation agent during the reactive dyeing process. The ozonation reaction exhibited almost instantaneous decolorization kinetics and a reasonable TOC reduction rate. It appeared to be stable under the investigated advanced oxidation conditions and outranked the other studied AOPs based on the above mentioned criteria. Besides, the electrical energy requirements based on the EE/O parameter (the electrical energy required per order of pollutant removal in 1 m3 wastewater) was calculated for the homogenous AOPs in terms of decolorization kinetics. In view of the electrical energy efficiency, ozonation and H2O2/UV-C oxidation at the selected treatment conditions appear to be promising candidates for full-scale dyehouse effluent decolorization.
Topics: Coloring Agents; Hydrogen Peroxide; Kinetics; Oxidants; Oxidants, Photochemical; Oxidation-Reduction; Ozone; Pigmentation; Titanium; Ultraviolet Rays; Water Purification
PubMed: 11902771
DOI: 10.1016/s0043-1354(01)00335-9 -
Chemical Communications (Cambridge,... Dec 2006A tetrahedrally coordinated iron in framework substituted microporous AlPO-5 catalysts are shown to be active and selective for the hydroxylation of benzene to phenol,...
A tetrahedrally coordinated iron in framework substituted microporous AlPO-5 catalysts are shown to be active and selective for the hydroxylation of benzene to phenol, using nitrous oxide as the oxidant.
Topics: Aluminum Compounds; Benzene; Catalysis; Iron; Nitrous Oxide; Oxidants; Oxidation-Reduction; Phenols; Phosphates; Temperature
PubMed: 17136259
DOI: 10.1039/b608982h -
Ground Water 2003The application of in situ chemical oxidation for dense, nonaqueous phase liquid (DNAPL) remediation requires delivery of substantial levels of oxidant chemicals into...
The application of in situ chemical oxidation for dense, nonaqueous phase liquid (DNAPL) remediation requires delivery of substantial levels of oxidant chemicals into the subsurface to degrade target DNAPLs and to satisfy natural oxidant demand. This practice can raise questions regarding changes in subsurface conditions, yet information regarding potential effects, especially at the field scale, has been lacking. This paper describes an evaluation of the effects on metals associated with in situ chemical oxidation using potassium permanganate at Launch Complex 34 (LC34), Cape Canaveral Air Station, Florida. At LC34, high concentrations of permanganate (1 to 2 wt%) were injected into the subsurface as part of a demonstration of DNAPL remediation technologies. In a companion experimental effort at the Colorado School of Mines, field samples were characterized and laboratory batch and mini-column studies were completed to assess effects of permanganate oxidation on metals in the subsurface one year after completion of the field demonstration. Results indicated there was potential for long-term immobilization of a portion of introduced manganese and no treatment-induced loss in subsurface permeability due to deposition of manganese oxides particles, which are a product of the oxidation reactions. Permanganate treatment did cause elevated manganese, chromium, and nickel concentrations in site ground water within the treated region. Some of these metals effects can be attenuated during downgradient flow through uncontaminated and untreated aquifer sediments.
Topics: Environmental Pollution; Geologic Sediments; Manganese Compounds; Metals, Heavy; Oxidants; Oxidation-Reduction; Oxides; Soil Pollutants; Water Movements; Water Pollutants
PubMed: 12873009
DOI: 10.1111/j.1745-6584.2003.tb02380.x -
Journal of Hazardous Materials Jun 2014Ozone (O3) oxidation combined with wet scrubbing is a promising method for the simultaneous removal of SO2 and NOx in flue gas. In this study, the O3 oxidation processes...
Ozone (O3) oxidation combined with wet scrubbing is a promising method for the simultaneous removal of SO2 and NOx in flue gas. In this study, the O3 oxidation processes of NO and SO2, as well as their coexistence, were investigated using an in situ IR spectrometer. Experimental results showed that the O3 concentration and the reaction temperature played critical roles in the O3 oxidation process of NO. Around 80°C, when inlet molar ratio of O3/NO was less than 1, NO was mainly oxidized to NO2, while when the ratio was greater than 1, NO would be further oxidized to NO3, N2O5, and HNO3. NO3 was the key intermediate product for the formation of N2O5 and HNO3. However, the subsequent reactions of NO3 were temperature dependence. With the increase of reaction temperature above 100°C, the concentration of NO2 increased whereas the concentrations of N2O5 and HNO3 decreased. The oxidation of SO2 by O3 was negligible and SO2 had little influence on the oxidation of NO in the simultaneous oxidation of NO and SO2. Finally, based on the in situ IR results, the oxidation mechanism is discussed and the reaction pathways are proposed.
Topics: Air Pollutants; Air Pollution; Nitrogen Oxides; Oxidants; Oxidation-Reduction; Ozone; Spectrophotometry, Infrared; Sulfur Dioxide
PubMed: 24801895
DOI: 10.1016/j.jhazmat.2014.04.027 -
Biochemical Pharmacology Mar 2019Ethanol administration is capable of inhibiting or delaying the partial hepatectomy (PH)-induced liver regeneration, probably altering liver metabolism by means of its...
Ethanol administration is capable of inhibiting or delaying the partial hepatectomy (PH)-induced liver regeneration, probably altering liver metabolism by means of its oxidative metabolism. Since the regenerating liver has increased capacity for oxidizing ethanol, the present study was aimed to address the contribution of the ethanol-oxidizing metabolic pathways in the regenerating liver cells. Isolated hepatocytes were prepared from control livers and from animals subjected to two-thirds PH. In both preparations, ethanol oxidation was largely increased by incubation with glucose and was highly sensitive to inhibitors of ethanol-oxidizing enzymatic pathways (alcohol dehydrogenase, catalase and cytochrome P-4502E1 activities). The latter led to a total blockade of ethanol disposal by control hepatocytes, while liver cells from PH-rats only showed an early 70-75% inhibition of ethanol catabolism with the inhibitors used. In regenerating hepatocytes, the enhanced ethanol oxidation was blocked by scavengers of reactive oxygen species, an effect that correlated with enhanced cytoplasmic lipid peroxidation by-products. Both cell preparations showed similar sensitivity to inhibitors for the malate-aspartate shuttle and mitochondrial electron transport chain; the shift of the cytoplasmic redox state was also quite similar after ethanol oxidation. A more oxidized mitochondrial redox state was found in hepatocytes from PH-rats and more shifted to the reduced state during ethanol oxidation this effect was not abolished by inhibiting alcohol dehydrogenase activity. In conclusion, data clearly show that an important fraction of ethanol is metabolized through a non-enzymatic-mediated oxidative event, which could largely contribute to the deleterious effect of ethanol on the proliferating liver.
Topics: Animals; Ethanol; Hepatectomy; Lipid Peroxidation; Liver Regeneration; Male; Oxidants; Oxidation-Reduction; Rats; Rats, Wistar; Reactive Oxygen Species
PubMed: 30625299
DOI: 10.1016/j.bcp.2019.01.003 -
Journal of the American Chemical Society Aug 2002Described here are oxidations of alkylaromatic compounds by dimanganese mu-oxo and mu-hydroxo dimers [(phen)(2)Mn(IV)(mu-O)(2)Mn(IV)(phen)(2)](4+) ([Mn(2)(O)(2)](4+)),...
Described here are oxidations of alkylaromatic compounds by dimanganese mu-oxo and mu-hydroxo dimers [(phen)(2)Mn(IV)(mu-O)(2)Mn(IV)(phen)(2)](4+) ([Mn(2)(O)(2)](4+)), [(phen)(2)Mn(IV)(mu-O)(2)Mn(III)(phen)(2)](3+) ([Mn(2)(O)(2)](3+)), and [(phen)(2)Mn(III)(mu-O)(mu-OH)Mn(III)(phen)(2)](3+) ([Mn(2)(O)(OH)](3+)). Dihydroanthracene, xanthene, and fluorene are oxidized by [Mn(2)(O)(2)](3+) to give anthracene, bixanthenyl, and bifluorenyl, respectively. The manganese product is the bis(hydroxide) dimer, [(phen)(2)Mn(III)(mu-OH)(2)Mn(II)(phen)(2)](3+) ([Mn(2)(OH)(2)](3+)). Global analysis of the UV/vis spectral kinetic data shows a consecutive reaction with buildup and decay of [Mn(2)(O)(OH)](3+) as an intermediate. The kinetics and products indicate a mechanism of hydrogen atom transfers from the substrates to oxo groups of [Mn(2)(O)(2)](3+) and [Mn(2)(O)(OH)](3+). [Mn(2)(O)(2)](4+) is a much stronger oxidant, converting toluene to tolyl-phenylmethanes and naphthalene to binaphthyl. Kinetic and mechanistic data indicate a mechanism of initial preequilibrium electron transfer for p-methoxytoluene and naphthalenes because, for instance, the reactions are inhibited by addition of [Mn(2)(O)(2)](3+). The oxidation of toluene by [Mn(2)(O)(2)](4+), however, is not inhibited by [Mn(2)(O)(2)](3+). Oxidation of a mixture of C(6)H(5)CH(3) and C(6)H(5)CD(3) shows a kinetic isotope effect of 4.3 +/- 0.8, consistent with C-H bond cleavage in the rate-determining step. The data indicate a mechanism of initial hydride transfer from toluene to [Mn(2)(O)(2)](4+). Thus, oxidations by manganese oxo dimers occur by three different mechanisms: hydrogen atom transfer, electron transfer, and hydride transfer. The thermodynamics of e(-), H(*), and H(-) transfers have been determined from redox potential and pK(a) measurements. For a particular oxidant and a particular substrate, the choice of mechanism is influenced both by the thermochemistry and by the intrinsic barriers. Rate constants for hydrogen atom abstraction by [Mn(2)(O)(2)](3+) and [Mn(2)(O)(OH)](3+) are consistent with their 79 and 75 kcal mol(-)(1) affinities for H(*). In the oxidation of p-methoxytoluene by [Mn(2)(O)(2)](4+), hydride transfer is thermochemically 24 kcal mol(-)(1) more facile than electron transfer; yet the latter mechanism is preferred. Thus, electron transfer has a substantially smaller intrinsic barrier than does hydride transfer in this system.
Topics: Anthracenes; Crystallography, X-Ray; Electrochemistry; Electrons; Fluorenes; Hydrocarbons, Aromatic; Hydrogen; Kinetics; Manganese; Manganese Compounds; Molecular Structure; Organometallic Compounds; Oxidants; Oxidation-Reduction; Oxides; Polysaccharides, Bacterial
PubMed: 12188675
DOI: 10.1021/ja020204a -
Molecules (Basel, Switzerland) Jul 2020Due to the coexistence of organic matter and iron in groundwater, a certain part of the iron is present as iron-organic complexes in the form of colloids and/or...
Due to the coexistence of organic matter and iron in groundwater, a certain part of the iron is present as iron-organic complexes in the form of colloids and/or dissolved complexes. The study was conducted to evaluate the impact of the type of oxidizing agent: O, Cl, HO, or KMnO, on the efficiency of the oxidation and removal of iron compounds from three groundwaters with significantly different contents and types of organic substances among which humic and fulvic acids occurred. This study shows that after the aeration and the oxidation with Cl and HO, the increasing content of dissolved hydrophilic organic substances containing aromatic rings in the raw water reduced the effectiveness of Fe(II) oxidation and the effectiveness of iron removal during the sedimentation process. This regularity was not found only when KMnO was used as the oxidant. After oxidation with HO, the highest number of organo-iron complexes and an increased concentration of dissolved organic carbon were found. High concentrations of organo-ferrous connections were also found in aerated water samples. The highest KMnO efficiency of removing iron and organic substances and reducing the color intensity and turbidity was due to the catalytic and adsorptive properties of the precipitated MnO, which also improved the sedimentation properties of the resultant oxidation products.
Topics: Adsorption; Groundwater; Humans; Humic Substances; Hydrogen Peroxide; Iron; Iron Compounds; Manganese Compounds; Oxidants; Oxidation-Reduction; Water Pollutants, Chemical
PubMed: 32722467
DOI: 10.3390/molecules25153380