RESUMO
Synchrotron X-ray footprinting (XF) is a growing structural biology technique that leverages radiation-induced chemical modifications via X-ray radiolysis of water to produce hydroxyl radicals that probe changes in macromolecular structure and dynamics in solution states of interest. The X-ray Footprinting of Biological Materials (XFP) beamline at the National Synchrotron Light Source II provides the structural biology community with access to instrumentation and expert support in the XF method, and is also a platform for development of new technological capabilities in this field. The design and implementation of a new high-throughput endstation device based around use of a 96-well PCR plate form factor and supporting diagnostic instrumentation for synchrotron XF is described. This development enables a pipeline for rapid comprehensive screening of the influence of sample chemistry on hydroxyl radical dose using a convenient fluorescent assay, illustrated here with a study of 26 organic compounds. The new high-throughput endstation device and sample evaluation pipeline now available at the XFP beamline provide the worldwide structural biology community with a robust resource for carrying out well optimized synchrotron XF studies of challenging biological systems with complex sample compositions.
Assuntos
Pegadas de Proteínas/métodos , Proteínas/química , Proteínas/efeitos da radiação , Síncrotrons/instrumentação , Desenho de Equipamento , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Conformação Proteica , Água/química , Raios XRESUMO
Radioprotectors with few side effects are useful for carbon-ion therapy, which directly induces clustering damage in DNA. With the aim of finding the most effective radioprotector, we investigated the effects of selected amino acids which might have chemical DNA-repair functions against therapeutic carbon ions. In the current study, we employed five amino acids: tryptophan (Trp), cysteine (Cys), methionine (Met), valine (Val) and alanine (Ala). Samples of supercoiled pBR322 plasmid DNA with a 17 mM amino acid were prepared in TE buffer (10 mM Tris, 1 mM ethylenediaminetetraacetic acid, pH 7.5). Phosphate buffered saline (PBS) was also used in assays of the 0.17 mM amino acid. The samples were irradiated with carbon-ion beams (290 MeV/u) on 6 cm spread-out Bragg peak at the National Institute of Radiological Sciences and Heavy Ion Medical Accelerator in Chiba, Japan. Breaks in the DNA were detected as changes in the plasmids and quantified by subsequent electrophoresis on agarose gels. DNA damage yields and protection factors for each amino acid were calculated as ratios relative to reagent-free controls. Trp and Cys showed radioprotective effects against plasmid DNA damage induced by carbon-ion beam, both in PBS and TE buffer, comparable to those of Met. The double-strand break (DSB) yields and protective effects of Trp were comparable to those of Cys. The yields of both single-strand breaks and DSBs correlated with the scavenging capacity of hydroxyl radicals (rate constant for scavenging hydroxyl radicals multiplied by the amino acid concentration) in bulk solution. These data indicate that the radioprotective effects of amino acids against plasmid DNA damage induced by carbon ions could be explained primarily by the scavenging capacity of hydroxyl radicals. These findings suggest that some amino acids, such as Trp, Cys and Met, have good potential as radioprotectors for preventing DNA damage in normal tissues in carbon-ion therapy.
Assuntos
Carbono/efeitos adversos , Dano ao DNA/efeitos da radiação , Radioterapia com Íons Pesados/efeitos adversos , Íons/efeitos adversos , Aminoácidos/química , Aminoácidos/genética , Aminoácidos/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Humanos , Radical Hidroxila/efeitos da radiação , Plasmídeos/química , Plasmídeos/genética , Plasmídeos/efeitos da radiação , Protetores contra Radiação/química , Protetores contra Radiação/efeitos da radiaçãoRESUMO
A standard Fricke dosimeter was used to measure the absorbed dose via the oxidation yields of Fe3+ ions in an aqueous environment induced by soft X rays within the "water window" spectral range. We also exploited the property of a neutral solution containing terephthalic acid as a tool for selective detection of OH radicals. Both dosimetric systems were irradiated using the experimental pulsed laser-plasma soft X-ray source as well as conventional 1.25-MeV gamma rays. Radiation chemical yields of Fe3+ ions and OH radicals were determined to be (5.13 ± 0.94) × 10-1 µmol·J-1 (4.95 ± 0.91 100eV-1) and (2.33 ± 0.35) × 10-2 µmol·J-1 (0.23 ± 0.03 100eV-1), respectively. Measurements were supported by Monte Carlo simulations to estimate the linear energy transfer of the water window radiation. The simulation results are in good agreement with expected linear energy transfer of ions inducing the same Fe3+ ion and OH radical radiation chemical yield.
Assuntos
Radical Hidroxila/química , Ferro/química , Radiometria , Raios X/efeitos adversos , Raios gama/efeitos adversos , Humanos , Radical Hidroxila/efeitos da radiação , Íons/química , Transferência Linear de Energia , Método de Monte Carlo , Oxirredução , Água/químicaRESUMO
The photocatalytic activities of reduced titanium dioxide (TiO2) materials have been investigated by measuring their ability to produce hydroxyl radicals under UV and visible light irradiation. Degussa P25 TiO2 was doped with nitrogen (N), fluorine (F), and/or phosphorus (P) and then subjected to surface modification employing a thermo-physicochemical process in the presence of reducing agent sodium borohydride (NaBH4). The reduced TiO2 materials were characterized by a number of X-ray, spectroscopic and imaging methods. Surface doping of TiO2 was employed to modulate the band gap energies into the visible wavelength region for better overlap with the solar spectrum. Hydroxyl radical generation, central to TiO2 photocatalytic water purification applications, was quantitated using coumarin as a trap under UV and visible light irradiation of the reduced TiO2 materials. At 350 nm irradiation, the yield of hydroxyl radicals generated by the reduced forms of TiO2 was nearly 90% of hydroxyl radicals generated by the Degussa P25 TiO2. Hydroxyl radical generation by these reduced forms of TiO2 was also observed under visible light irradiation (419 and 450 nm). These results demonstrated that simple surface modification of doped TiO2 can lead to visible light activity, which is important for more economical solar-driven applications of TiO2 photocatalysis.
Assuntos
Radical Hidroxila/química , Processos Fotoquímicos , Titânio/química , Flúor/química , Radical Hidroxila/efeitos da radiação , Luz , Nitrogênio/química , Fósforo/química , Titânio/efeitos da radiação , Raios UltravioletaRESUMO
The chemistry of oxidants and their precursors (oxidants*) plays a central role in outdoor environments but its importance in indoor air remains poorly understood. Ozone (O3) chemistry is important in some indoor environments and, until recently, ozone was thought to be the dominant oxidant indoors. There is now evidence that formation of the hydroxyl radical by photolysis of nitrous acid (HONO) and formaldehyde (HCHO) may be important indoors. In the past few years, high time-resolution measurements of oxidants* indoors have become more common and the importance of event-based release of oxidants* during activities such as cleaning has been proposed. Here we review the current understanding of oxidants* indoors, including drivers of the formation and loss of oxidants*, levels of oxidants* in indoor environments, and important directions for future research.
Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Radical Hidroxila/análise , Iluminação , Oxidantes , Fotólise , Poluentes Atmosféricos/efeitos da radiação , Formaldeído/análise , Formaldeído/efeitos da radiação , Radical Hidroxila/efeitos da radiação , Ácido Nitroso/análise , Ácido Nitroso/efeitos da radiação , Ozônio/análise , Ozônio/efeitos da radiaçãoRESUMO
The success of radiotherapy relies on tumor-specific delivery of radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties by changing only the introduced bissilylated organosilica precursors. The biodegradable thioether-hybridized HMONs are chosen for efficient co-delivery of tert-butyl hydroperoxide (TBHP) and iron pentacarbonyl (Fe(CO)5). Distinct from conventional RT, radiodynamic therapy (RDT) is developed by taking advantage of X-ray-activated peroxy bond cleavage within TBHP to generate â¢OH, which can further attack Fe(CO)5 to release CO molecules for gas therapy. Detailed in vitro and in vivo studies reveal the X-ray-activated cascaded release of â¢OH and CO molecules from TBHP/Fe(CO)5 co-loaded PEGylated HMONs without reliance on oxygen, which brings about remarkable destructive effects against both normoxic and hypoxic cancers.
Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia/métodos , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos/efeitos da radiação , Neoplasias/terapia , Animais , Monóxido de Carbono/química , Feminino , Células Hep G2 , Humanos , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Compostos de Ferro/administração & dosagem , Camundongos , Camundongos Nus , Nanopartículas/química , Compostos de Organossilício/síntese química , Tamanho da Partícula , Polietilenoglicóis/química , Porosidade , Células RAW 264.7 , Resultado do Tratamento , Raios X , Ensaios Antitumorais Modelo de Xenoenxerto , terc-Butil Hidroperóxido/administração & dosagem , terc-Butil Hidroperóxido/efeitos da radiaçãoRESUMO
Hydroxyl radical protein footprinting (HRPF) is a powerful method for measuring protein topography, allowing researchers to monitor events that alter the solvent accessible surface of a protein (e.g., ligand binding, aggregation, conformational changes, etc.) by measuring changes in the apparent rate of reaction of portions of the protein to hydroxyl radicals diffusing in solution. Fast Photochemical Oxidation of Proteins (FPOP) offers an ultrafast benchtop method for radical generation for HRPF, photolyzing hydrogen peroxide using a UV laser to generate high concentrations of hydroxyl radicals that are consumed on roughly a microsecond time scale. The broad reactivity of hydroxyl radicals means that almost anything added to the solution (e.g., ligands, buffers, excipients, etc.) will scavenge hydroxyl radicals, altering their half-life and changing the effective radical concentration experienced by the protein. Similarly, minute changes in peroxide concentration, laser fluence, and buffer composition can alter the effective radical concentration, making reproduction of data challenging. Here, we present a simple method for radical dosimetry that can be carried out as part of the FPOP workflow, allowing for measurement of effective radical concentration in real time. Additionally, by modulating the amount of radical generated, we demonstrate that effective hydroxyl radical yields in FPOP HRPF experiments carried out in buffers with widely differing levels of hydroxyl radical scavenging capacity can be compensated on the fly, yielding statistically indistinguishable results for the same conformer. This method represents a major step in transforming FPOP into a robust and reproducible technology capable of probing protein structure in a wide variety of contexts.
Assuntos
Adenina/química , Fibrinopeptídeo B/química , Radical Hidroxila/química , Mioglobina/química , Pegadas de Proteínas/métodos , Adenina/análise , Radical Hidroxila/efeitos da radiação , Oxirredução , Espectrofotometria Ultravioleta , Raios UltravioletaRESUMO
The thermal decomposition of 9,10 diphenylanthracene peroxide (DPAO2) generates DPA and a mix of triplet and singlet molecular oxygen. For DPAO2 the efficiency to produce singlet molecular oxygen is 0.35. On the other hand, it has shown that many thermal reactions can be carried out through the interaction of molecules with ultrasound. Ultrasound irradiation can create hydrodynamic stress (sonomechanical process), inertial cavitation (pyrolitic process) and long range effects mediated by radicals or ROS. Sonochemical reactions can be originated by pyrolytic like process, shock mechanical waves, thermal reactions and radical and ROS mediated reactions. Sonolysis of pure water can yield hydrogen or hydroxyl radicals and hydrogen peroxide (ROS). When DPAO2 in 1,4 dioxane solution is treated with 20 or 24kHz and different power intensity the production of molecular singlet oxygen is observed. Specific scavengers like tetracyclone (TC) are used to demonstrate it. The efficiency now is 0.85 showing that the sonochemical process is much more efficient that the thermal one. Another endoperoxide, artemisinin was also studied. Unlike the concept of photosensitizer of photodynamic therapy, in spite of large amount of reported results in literature, the term sonosensitizer and the sonosensitization process are not well defined. We define sonosensitized reaction as one in which a chemical species decompose as consequence of cavitation phenomena producing ROS or other radicals and some other target species does undergo a chemical reaction. The concept could be reach rapidly other peroxides which are now under experimental studies. For artemisinin, an important antimalarian and anticancer drug, was established that ultrasound irradiation increases the effectiveness of the treatment but without any explanation. We show that artemisinin is an endoperoxide and behaves as a sonosensitizer in the sense of our definition.
Assuntos
Artemisininas/química , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Espécies Reativas de Oxigênio/química , Antracenos/química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Radicais Livres/química , Humanos , Radical Hidroxila/efeitos da radiação , Espécies Reativas de Oxigênio/efeitos da radiação , Oxigênio Singlete/química , Ondas UltrassônicasRESUMO
Hydrogen peroxide UV photolysis is among the most widely used advanced oxidation processes (AOPs) for the destruction of trace organics in waters destined for reuse. Previous kinetic models of hydrogen peroxide photolysis focus on the dynamics of hydroxyl radical production and consumption, as well as the reaction of the target organic with hydroxyl radicals. However, the rate of target destruction may also be affected by radical scavenging by reaction products. In this work, we build a predictive kinetic model for the destruction of p-cresol by hydrogen peroxide photolysis based on a complete reaction mechanism that includes reactions of intermediates with hydroxyl radicals. The results show that development of a predictive kinetic model to evaluate process performance requires consideration of the complete reaction mechanism, including reactions of intermediates with hydroxyl radicals.
Assuntos
Cresóis/química , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Raios Ultravioleta , Poluentes Químicos da Água/química , Cinética , Modelos Químicos , Oxirredução , Fotólise , Purificação da Água/métodosRESUMO
This study addresses the preparation and characterization of hybrid films prepared from Titanium dioxide (TiO2) Pickering stabilized acrylic polymeric dispersion as well as their bacterial inactivation efficiency under sunlight irradiation. Complete bacterial inactivation under low intensity simulated solar light irradiation (55 mW/cm(2)) was observed within 240 min for the films containing 10 weight based on monomers (wbm) % of TiO2, whereas 360 min were needed for the films containing 20 wbm% of TiO2. The hybrid films showed repetitive Escherichia coli (E. coli) inactivation under light irradiation. TiO2 released from the films surfaces was measured by inductively coupled plasma mass spectrometry (IPC-MS), obtaining values of â¼ 0.5 and 1 ppb/cm(2) for the films containing 10 wbm% and 20 wbm% of TiO2, respectively, far below the allowed cytotoxicity level for TiO2 (200 ppb). Transmission electron microscopy (TEM) of the hybrid films showed that TiO2 nanoparticles (NPs) were located at the polymer particle's surface forming a continuous inorganic network inside the film matrix. Atomic force microscopy (AFM) images showed differences in the TiO2 dispersion between the air-film and film-substrate interfaces. Films containing 10 wbm% of TiO2 had higher roughness (Rg) at both interfaces than the one containing 20 wbm% of TiO2 inducing an increase in the bacterial adhesion as well as the bacterial inactivation kinetics. The highly oxidative OH-radicals participating in the bacterial inactivation were determined by fluorescence.
Assuntos
Acrilatos/química , Acrilatos/efeitos da radiação , Antibacterianos/química , Antibacterianos/efeitos da radiação , Luz Solar , Titânio/química , Titânio/efeitos da radiação , Aderência Bacteriana/efeitos dos fármacos , Aderência Bacteriana/efeitos da radiação , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Microscopia de Força Atômica , Ácidos Ftálicos/química , Propriedades de SuperfícieRESUMO
Using the EPR spin trapping technique, we prove that simultaneous reactions take place in illuminated suspensions of TiO2 in aqueous carbonate solutions (pH ≈ 7). The adsorbed HCO3(-) is reduced to formate as directly made evident by the detection of formate radicals (ËCO2(-)). In addition, the amount of OHË radicals from the photo-oxidation of water shows a linear dependence on the concentration of bicarbonate, indicating that electron scavenging by HCO3(-) increases the lifetime of holes. In a weakly alkaline medium, photo-oxidation of HCO3(-)/CO3(2-) to ËCO3(-) interferes with the oxidation of water. A comparative analysis of different TiO2 samples shows that formation of ËCO2(-) is influenced by factors related to the nature of the surface, once expected surface area effects are accounted for. Modification of the TiO2 surface with noble metal nanoparticles does not have unequivocal benefits: the overall activity improves with Pd and Rh but not with Ru, which favours HCO3(-) photo-oxidation even at pH = 7. In general, identification of radical intermediates of oxidation and reduction reactions can provide useful mechanistic information that may be used in the development of photocatalytic systems for the reduction of CO2 also stored in the form of carbonates.
Assuntos
Bicarbonatos/química , Dióxido de Carbono/química , Processos Fotoquímicos , Titânio/química , Água/química , Bicarbonatos/efeitos da radiação , Dióxido de Carbono/efeitos da radiação , Espectroscopia de Ressonância de Spin Eletrônica , Fluorescência , Formiatos/química , Formiatos/efeitos da radiação , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Modelos Lineares , Oxirredução , Detecção de Spin , Propriedades de Superfície , Suspensões , Titânio/efeitos da radiaçãoRESUMO
The density of hydroxyl radicals (·OH) produced in aqueous samples by exposure to X-ray or carbon-ion beams was investigated. The generation of ·OH was detected by the electron paramagnetic resonance (EPR) spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin-trapping agent. When the concentration of DMPO is in excess of the generated ·OH, the production of DMPO-OH (spin-trapped ·OH) should be saturated. Reaction mixtures containing several concentrations (0.5-1685 mM) of DMPO were then irradiated by a 32 Gy 290 MeV carbon-ion beam (C290-beam) or X-ray. C290-beam irradiation was performed at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, National Institute of Radiological Sciences, Chiba, Japan), applying different linear energy transfers (LET) (20-169 keV/µm). The amount of DMPO-OH in the irradiated samples was detected by EPR spectroscopy. The generation of DMPO-OH increased with the concentration of initial DMPO, displayed a shoulder around 3.3 mM DMPO, and reached a plateau. This plateau suggests that the generated ·OH were completely trapped. Another linear increase in DMPO-OH measured in solutions with higher DMPO concentrations suggested very dense ·OH generation (>1.7 M). Generation of ·OH is expected to be localized on the track of the radiation beam, because the maximum concentration of measured DMPO-OH was 40 µM. These results suggested that both sparse (≈3.3 mM) and dense (>1.7 M) ·OH generation occurred in the irradiated samples. The percentage of dense ·OH generation increased with increasing LET. Different types of dense ·OH generation may be expected for X-ray and C290-beams.
Assuntos
Carbono/química , Íons Pesados , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Água/química , Radicais Livres/química , Radicais Livres/efeitos da radiação , Radioterapia com Íons Pesados/métodos , Soluções , Raios XRESUMO
Chromophoric dissolved organic matter (CDOM) in surface waters is a photochemical source of several transient species such as CDOM triplet states ((3)CDOM*), singlet oxygen ((1)O2) and the hydroxyl radical (OH). By irradiation of lake water samples, it is shown here that the quantum yields for the formation of these transients by CDOM vary depending on the irradiation wavelength range, in the order UVB > UVA > blue. A possible explanation is that radiation at longer wavelengths is preferentially absorbed by the larger CDOM fractions, which show lesser photoactivity compared to smaller CDOM moieties. The quantum yield variations in different spectral ranges were definitely more marked for (3)CDOM* and OH compared to (1)O2. The decrease of the quantum yields with increasing wavelength has important implications for the photochemistry of surface waters, because long-wavelength radiation penetrates deeper in water columns compared to short-wavelength radiation. The average steady-state concentrations of the transients ((3)CDOM*, (1)O2 and OH) were modelled in water columns of different depths, based on the experimentally determined wavelength trends of the formation quantum yields. Important differences were found between such modelling results and those obtained in a wavelength-independent quantum yield scenario.
Assuntos
Substâncias Húmicas/efeitos da radiação , Radical Hidroxila/efeitos da radiação , Lagos/química , Oxigênio/efeitos da radiação , Modelos Teóricos , Processos FotoquímicosRESUMO
Deferiprone (L1) is an effective iron-chelating drug that is widely used for the treatment of iron-overload diseases. It is known that in aqueous solutions Fe(2+) and Fe(3+) ions can produce hydroxyl radicals via Fenton and photo-Fenton reactions. Although previous studies with Fe(2+) have reported ferroxidase activity by L1 followed by the formation of Fe(3+) chelate complexes and potential inhibition of Fenton reaction, no detailed data are available on the molecular antioxidant mechanisms involved. Similarly, in vitro studies have also shown that L1-Fe(3+) complexes exhibit intense absorption bands up to 800nm and might be potential sources of phototoxicity. In this study we have applied an EPR spin trapping technique to answer two questions: (1) does L1 inhibit the Fenton reaction catalyzed by Fe(2+) and Fe(3+) ions and (2) does UV-Vis irradiation of the L1-Fe(3+) complex result in the formation of reactive oxygen species. PBN and TMIO spin traps were used for detection of oxygen free radicals, and TEMP was used to trap singlet oxygen if it was formed via energy transfer from L1 in the triplet excited state. It was demonstrated that irradiation of Fe(3+) aqua complexes by UV and visible light in the presence of spin traps results in the appearance of an EPR signal of the OH spin adduct (TMIO-OH, a(N)=14.15G, a(H)=16.25G; PBN-OH, a(N)=16.0G, a(H)=2.7G). The presence of L1 completely inhibited the OH radical production. The mechanism of OH spin adduct formation was confirmed by the detection of methyl radicals in the presence of dimethyl sulfoxide. No formation of singlet oxygen was detected under irradiation of L1 or its iron complexes. Furthermore, the interaction of L1 with Fe(2+) ions completely inhibited hydroxyl radical production in the presence of hydrogen peroxide. These findings confirm an antioxidant targeting potential of L1 in diseases related to oxidative damage.
Assuntos
Radical Hidroxila/química , Radical Hidroxila/metabolismo , Quelantes de Ferro/farmacologia , Ferro/farmacologia , Piridonas/farmacologia , Deferiprona , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Radical Hidroxila/efeitos da radiação , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Detecção de Spin , Raios UltravioletaRESUMO
Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 10(8) dm(3) mol(-1) s(-1) and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10-1000 µmol dm(-3)) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid.
Assuntos
Antipirina/análogos & derivados , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Plasmídeos/química , Plasmídeos/efeitos da radiação , Antipirina/química , Sequência de Bases/efeitos da radiação , Adutos de DNA/química , Adutos de DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Edaravone , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Dados de Sequência Molecular , Oxirredução/efeitos da radiação , Plasmídeos/genética , Radiólise de Impulso , Doses de RadiaçãoRESUMO
The effect of oxidation on redox and cytotoxic properties of copper complex of amyloid beta (Aß) peptide was studied by gamma radiolysis. The oxidation of Aß1-16 and Aß1-16/Cu(II) complex was carried out using hydroxyl ((â¢)OH) radicals produced by gamma radiolysis and the products were analyzed using mass spectrometry. The presence of Cu(II) was found to enhance the oxidation of Aß1-16 peptide. The oxidation of residues Asp1, His6, and His13 was enhanced due to their involvement in copper binding. The oxidation of His residues of Aß1-16 peptide, which are chiefly responsible for copper binding, resulted in altered redox properties and subsequently in higher cytotoxicity of the Aß1-16 peptide in SH-SY5Y cells.
Assuntos
Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/toxicidade , Cobre/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/toxicidade , Peptídeos beta-Amiloides/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Radical Hidroxila/química , Radical Hidroxila/farmacologia , Radical Hidroxila/efeitos da radiação , Oxirredução/efeitos dos fármacos , Fragmentos de Peptídeos/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
First-principles simulations suggest that additional OH formation in the troposphere can result from ozone interactions with the surface of cloud droplets. Ozone exhibits an affinity for the air-water interface, which modifies its UV and visible light spectroscopic signatures and photolytic rate constant in the troposphere. Ozone cross sections on the red side of the Hartley band (290- to 350-nm region) and in the Chappuis band (450-700 nm) are increased due to electronic ozone-water interactions. This effect, combined with the potential contribution of the O3 + hν â O((3)P) + O2(X(3)Σg(-)) photolytic channel at the interface, leads to an enhancement of the OH radical formation rate by four orders of magnitude. This finding suggests that clouds can influence the overall oxidizing capacity of the troposphere on a global scale by stimulating the production of OH radicals through ozone photolysis by UV and visible light at the air-water interface.
Assuntos
Atmosfera/química , Ozônio/química , Ozônio/efeitos da radiação , Água , Gases/química , Gases/efeitos da radiação , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Processos Fotoquímicos , Fotólise , Espectrofotometria , Espectrofotometria Ultravioleta , Raios Ultravioleta , Água/químicaRESUMO
PURPOSE: The hydroxyl radical ((â)OH)-induced oxidation reactions of isomeric hydroxy naphthoquinones (generally having anti-tumor activities) namely, lawsone and juglone, were carried out and the reaction mechanism was elucidated. MATERIALS AND METHODS: The degradation products from the reaction of (â)OH (produced by H(2)O(2)/UV) with lawsone and juglone were analyzed using a liquid chromatography quadrupole-time-of-flight mass spectrometer (LC-Q-TOF-MS). The transient intermediate studies were investigated using picosecond pulse radiolysis technique. RESULTS: Mono hydroxylated and dihydroxylated adducts of both lawsone and juglone were identified from the product analysis. The isomeric mono-hydroxylated adducts of lawsone were confirmed using survival yield (SY) analysis. The hydroxylated adducts of lawsone also underwent dimerization reaction. The transient spectral analysis using pulse radiolysis studies revealed the formation of hydroxycyclohexadienyl type radical of both lawsone and juglone as the initially formed intermediate. CONCLUSIONS: The (â)OH-induced reactions of both lawsone and juglone result in the mono and di-hydoxylated derivatives. The demonstration of the various isomeric products using mass spectrometry is a clear proof of the addition probability of (â)OH at different positions of lawsone and juglone, which is generally a difficult task using other analytical techniques.
Assuntos
Naftoquinonas/química , Naftoquinonas/efeitos da radiação , Cromatografia Líquida , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Modelos Químicos , Estrutura Molecular , Oxirredução , Radiólise de Impulso , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Raios UltravioletaRESUMO
The degradation of cylindrospermopsin (CYN), a widely distributed and highly toxic cyanobacterial toxin (cyanotoxin), remains poorly elucidated. In this study, the mechanism of CYN destruction by UV-254 nm/H2O2 advanced oxidation process (AOP) was investigated by mass spectrometry. Various byproducts identified indicated three common reaction pathways: hydroxyl addition (+16 Da), alcoholic oxidation or dehydrogenation (-2 Da), and elimination of sulfate (-80 Da). The initiation of the degradation was observed at the hydroxymethyl uracil and tricyclic guanidine groups; uracil moiety cleavage/fragmentation and further ring-opening of the alkaloid were also noted at an extended reaction time or higher UV fluence. The degradation rates of CYN decreased and less byproducts (species) were detected using natural water matrices; however, CYN was effectively eliminated under extended UV irradiation. This study demonstrates the efficiency of CYN degradation and provides a better understanding of the mechanism of CYN degradation by hydroxyl radical, a reactive oxygen species that can be generated by most AOPs and is present in natural water environment.
Assuntos
Toxinas Bacterianas/química , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Toxinas Marinhas/química , Microcistinas/química , Uracila/análogos & derivados , Alcaloides/química , Toxinas Bacterianas/efeitos da radiação , Biodegradação Ambiental/efeitos da radiação , Toxinas de Cianobactérias , Filtração , Radical Hidroxila/efeitos da radiação , Cinética , Toxinas Marinhas/efeitos da radiação , Microcistinas/efeitos da radiação , Ohio , Oxirredução/efeitos da radiação , Dióxido de Silício/química , Sulfatos/química , Raios Ultravioleta , Uracila/química , Uracila/efeitos da radiação , Qualidade da ÁguaRESUMO
Purine compounds xanthosine, caffeine, inosine-5'-monophosphate and guanosine-5'-monophosphate in the concentration range of 0.02-1 mmol/L exhibit antioxidant properties in vitro, significantly reducing the formation of hydrogen peroxide and hydroxyl radicals induced by X-rays in aqueous solutions and preventing the formation of 8-oxoguanine in DNA solutions. These compounds neutralize the long-lived protein radicals in vitro induced by radiation. In vivo they exhibit pronounced radiotherapeutic properties, increasing the survival rate of mice up to 50% by intraperitoneal injection (45 mg/kg) after the exposure to a lethal dose of 7 Gy. The tested compounds stimulate hemopoiesis, increasing the number of white blood cells and platelets in the peripheral blood of animals in postradiation period, as well as radiation recovery of DNA damage when administered both before and after irradiation. These purine compounds can be considered as potentially promising preventive and therapeutic agents to reduce the risk of the pathological effects of ionizing radiation on the body of mammals.