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Biomolecules Oct 2023We examined the reaction of hydroxyl radicals (HO) and sulfate radical anions (SO), which is generated by ionizing radiation in aqueous solutions under anoxic...
We examined the reaction of hydroxyl radicals (HO) and sulfate radical anions (SO), which is generated by ionizing radiation in aqueous solutions under anoxic conditions, with an alternating GC doubled-stranded oligodeoxynucleotide (ds-ODN), i.e., the palindromic 5'-d(GCGCGC)-3'. In particular, the optical spectra of the intermediate species and associated kinetic data in the range of ns to ms were obtained via pulse radiolysis. Computational studies by means of density functional theory (DFT) for structural and time-dependent DFT for spectroscopic features were performed on 5'-d(GCGC)-3'. Comprehensively, our results suggest the addition of HO to the G:C pair moiety, affording the [8-HO-G:C] detectable adduct. The previous reported spectra of one-electron oxidation of a variety of ds-ODN were assigned to [G(-H):C] after deprotonation. Regarding 5'-d(GCGCGC)-3' ds-ODN, the spectrum at 800 ns has a completely different spectral shape and kinetic behavior. By means of calculations, we assigned the species to [G:C/C:G], in which the electron hole is predicted to be delocalized on the two stacked base pairs. This transient species was further hydrated to afford the [8-HO-G:C] detectable adduct. These remarkable findings suggest that the double-stranded alternating GC sequences allow for a new type of electron hole stabilization via delocalization over the whole sequence or part of it.
Topics: Oligonucleotides; Hydroxyl Radical; Electrons; Free Radicals; Oxidation-Reduction; Oligodeoxyribonucleotides
PubMed: 37892175
DOI: 10.3390/biom13101493 -
International Journal of Molecular... Jun 2019Retinoids are present in human tissues exposed to light and under increased risk of oxidative stress, such as the retina and skin. Retinoid cation radicals can be formed...
Retinoids are present in human tissues exposed to light and under increased risk of oxidative stress, such as the retina and skin. Retinoid cation radicals can be formed as a result of the interaction between retinoids and other radicals or photoexcitation with light. It has been shown that such semi-oxidized retinoids can oxidize certain amino acids and proteins, and that α-tocopherol can scavenge the cation radicals of retinol and retinoic acid. The aim of this study was to determine (i) whether β-, γ-, and δ-tocopherols can also scavenge these radicals, and (ii) whether tocopherols can scavenge the cation radicals of another form of vitamin A-retinal. The retinoid cation radicals were generated by the pulse radiolysis of benzene or aqueous solution in the presence of a selected retinoid under oxidizing conditions, and the kinetics of retinoid cation radical decays were measured in the absence and presence of different tocopherols, Trolox or urate. The bimolecular rate constants are the highest for the scavenging of cation radicals of retinal, (7 to 8) × 10 M·s, followed by retinoic acid, (0.03 to 5.6) × 10 M·s, and retinol, (0.08 to 1.6) × 10 M·s. Delta-tocopherol is the least effective scavenger of semi-oxidized retinol and retinoic acid. The hydrophilic analogue of α-tocopherol, Trolox, is substantially less efficient at scavenging retinoid cation radicals than α-tocopherol and urate, but it is more efficient at scavenging the cation radicals of retinoic acid and retinol than δ-tocopherol. The scavenging rate constants indicate that tocopherols can effectively compete with amino acids and proteins for retinoid cation radicals, thereby protecting these important biomolecules from oxidation. Our results provide another mechanism by which tocopherols can diminish the oxidative damage to the skin and retina and thereby protect from skin photosensitivity and the development and/or progression of changes in blinding retinal diseases such as Stargardt's disease and age-related macular degeneration (AMD).
Topics: Cations; Chromans; Free Radical Scavengers; Retinoids; Tocopherols; Uric Acid
PubMed: 31181693
DOI: 10.3390/ijms20112799 -
The Journal of Biological Chemistry Dec 2017Cytochrome P450cam (CYP101Fe) regioselectively hydroxylates camphor. Possible hydroxylating intermediates in the catalytic cycle of this well-characterized enzyme have...
Cytochrome P450cam (CYP101Fe) regioselectively hydroxylates camphor. Possible hydroxylating intermediates in the catalytic cycle of this well-characterized enzyme have been proposed on the basis of experiments carried out at very low temperatures and shunt reactions, but their presence has not yet been validated at temperatures above 0 °C during a normal catalytic cycle. Here, we demonstrate that it is possible to mimic the natural catalytic cycle of CYP101Fe by using pulse radiolysis to rapidly supply the second electron of the catalytic cycle to camphor-bound CYP101[FeO] Judging by the appearance of an absorbance maximum at 440 nm, we conclude that CYP101[FeOOH] (compound 0) accumulates within 5 μs and decays rapidly to CYP101Fe, with a of 9.6 × 10 s All processes are complete within 40 μs at 4 °C. Importantly, no transient absorbance bands could be assigned to CYP101[FeOpor] (compound 1) or CYP101[FeO] (compound 2). However, indirect evidence for the involvement of compound 1 was obtained from the kinetics of formation and decay of a tyrosyl radical. 5-Hydroxycamphor was formed quantitatively, and the catalytic activity of the enzyme was not impaired by exposure to radiation during the pulse radiolysis experiment. The rapid decay of compound 0 enabled calculation of the limits for the Gibbs activation energies for the conversions of compound 0 → compound 1 → compound 2 → CYP101Fe, yielding a Δ of 45, 39, and 39 kJ/mol, respectively. At 37 °C, the steps from compound 0 to the iron(III) state would take only 4 μs. Our kinetics studies at 4 °C complement the canonical mechanism by adding the dimension of time.
Topics: Binding Sites; Camphor 5-Monooxygenase; Catalysis; Cytochrome P-450 Enzyme System; Electron Transport; Electrons; Ferric Compounds; Kinetics; Models, Molecular; Oxidation-Reduction
PubMed: 29109145
DOI: 10.1074/jbc.M117.813683 -
Molecules (Basel, Switzerland) Nov 2014The kinetics and spectral characteristics of the transients formed in the reactions of •OH and •N3 with quinoxalin-2(1H)-one (Q), its methyl derivative,...
The kinetics and spectral characteristics of the transients formed in the reactions of •OH and •N3 with quinoxalin-2(1H)-one (Q), its methyl derivative, 3-methylquinoxalin-2(1H)-one (3-MeQ) and pyrazin-2-one (Pyr) were studied by pulse radiolysis in aqueous solutions at pH 7. The transient absorption spectra recorded in the reactions of •OH with Q and 3-MeQ consisted of an absorption band with λmax = 470 nm assigned to the OH-adducts on the benzene ring, and a second band with λmax = 390 nm (for Q) and 370 nm (for 3-MeQ) assigned, inter alia, to the N-centered radicals on a pyrazin-2-one ring. The rate constants of the reactions of •OH with Q and 3-MeQ were found to be in the interval (5.9-9.7) × 109 M-1·s-1 and were assigned to their addition to benzene and pyrazin-2-one rings and H-abstraction from the pyrazin-2-one nitrogen. In turn, the transient absorption spectrum observed in the reaction of •N3 exhibits an absorption band with λmax = 350 nm. This absorption was assigned to the N-centered radical on the Pyr ring formed after deprotonation of the respective radical cation resulting from one-electron oxidation of 3-MeQ. The rate constant of the reaction of •N3 with 3 MeQ was found to be (6.0 ± 0.5) × 109 M-1·s-1. Oxidation of 3-MeQ by •N3 and Pyr by •OH and •N3 confirms earlier spectral assignments. With the rate constant of the •OH radical with Pyr (k = 9.2 ± 0.2) × 109 M-1·s‒1, a primary distribution of the •OH attack was estimated nearly equal between benzene and pyrazin-2-one rings.
Topics: Benzene; Electrons; Free Radicals; Hydrogen-Ion Concentration; Hydroxyl Radical; Kinetics; Nitrogen; Oxidation-Reduction; Pulse Radiolysis; Quinoxalines
PubMed: 25415477
DOI: 10.3390/molecules191119152 -
Medical Physics Mar 2019Track structure simulation codes can accurately reproduce the stochastic nature of particle-matter interactions in order to evaluate quantitatively radiation damage in...
PURPOSE
Track structure simulation codes can accurately reproduce the stochastic nature of particle-matter interactions in order to evaluate quantitatively radiation damage in biological cells such as DNA strand breaks and base damage. Such simulations handle large numbers of secondary charged particles and molecular species created in the irradiated medium. Every particle and molecular species are tracked step-by-step using a Monte Carlo method to calculate energy loss patterns and spatial distributions of molecular species inside a cell nucleus with high spatial accuracy. The Geant4-DNA extension of the Geant4 general-purpose Monte Carlo simulation toolkit allows for such track structure simulations and can be run on CPUs. However, long execution times have been observed for the simulation of DNA damage in cells. We present in this work an improvement of the computing performance of such simulations using ultraparallel processing on a graphical processing unit (GPU).
METHODS
A new Monte Carlo simulator named MPEXS-DNA, allowing high computing performance by using a GPU, has been developed for track structure and radiolysis simulations at the subcellular scale. MPEXS-DNA physics and chemical processes are based on Geant4-DNA processes available in Geant4 version 10.02 p03. We have reimplemented the Geant4-DNA process codes of the physics stage (electromagnetic processes of charged particles) and the chemical stage (diffusion and chemical reactions for molecular species) for microdosimetry simulation by using the CUDA language. MPEXS-DNA can calculate a distribution of energy loss in the irradiated medium caused by charged particles and also simulate production, diffusion, and chemical interactions of molecular species from water radiolysis to quantitatively assess initial damage to DNA. The validation of MPEXS-DNA physics and chemical simulations was performed by comparing various types of distributions, namely the radial dose distributions for the physics stage, and the G-value profiles for each chemical product and their linear energy transfer dependency for the chemical stage, to existing experimental data and simulation results obtained by other simulation codes, including PARTRAC.
RESULTS
For physics validation, radial dose distributions calculated by MPEXS-DNA are consistent with experimental data and numerical simulations. For chemistry validation, MPEXS-DNA can also reproduce G-value profiles for each molecular species with the same tendency as existing experimental data. MPEXS-DNA also agrees with simulations by PARTRAC reasonably well. However, we have confirmed that there are slight discrepancies in G-value profiles calculated by MPEXS-DNA for molecular species such as H and H O when compared to experimental data and PARTRAC simulations. The differences in G-value profiles between MPEXS-DNA and PARTRAC are caused by the different chemical reactions considered. MPEXS-DNA can drastically boost the computing performance of track structure and radiolysis simulations. By using NVIDIA's GPU devices adopting the Volta architecture, MPEXS-DNA has achieved speedup factors up to 2900 against Geant4-DNA simulations with a single CPU core.
CONCLUSION
The MPEXS-DNA Monte Carlo simulation achieves similar accuracy to Monte Carlo simulations performed using other codes such as Geant4-DNA and PARTRAC, and its predictions are consistent with experimental data. Notably, MPEXS-DNA allows calculations that are, at maximum, 2900 times faster than conventional simulations using a CPU.
Topics: Computer Simulation; DNA; DNA Damage; Electrons; Humans; Linear Energy Transfer; Models, Chemical; Monte Carlo Method; Pulse Radiolysis; Radiochemistry; User-Computer Interface; Water
PubMed: 30593679
DOI: 10.1002/mp.13370 -
Journal of Radiation Research Jan 2015Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis...
Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA.
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.
Topics: Antipyrine; Base Sequence; DNA Adducts; DNA Damage; DNA Repair; Dose-Response Relationship, Radiation; Edaravone; Free Radical Scavengers; Hydroxyl Radical; Molecular Sequence Data; Oxidation-Reduction; Plasmids; Pulse Radiolysis; Radiation Dosage
PubMed: 25212600
DOI: 10.1093/jrr/rru079 -
Molecules (Basel, Switzerland) Oct 2019The reaction of hydroxyl radical (HO) with DNA produces many primary reactive species and many lesions as final products. In this study, we have examined the optical...
The reaction of hydroxyl radical (HO) with DNA produces many primary reactive species and many lesions as final products. In this study, we have examined the optical spectra of intermediate species derived from the reaction of HO with a variety of single- and double-stranded oligodeoxynucleotides and ct-DNA in the range of 1 μs to 1 ms by pulse radiolysis using an Intensified Charged Coupled Device (ICCD) camera. Moreover, we applied our published analytical protocol based on an LC-MS/MS system with isotopomeric internal standards to enable accurate and precise measurements of purine lesion formation. In particular, the simultaneous measurement of the four purine 5',8-cyclo-2'-deoxynucleosides (cPu) and two 8-oxo-7,8-dihydro-2'-deoxypurine (8-oxo-Pu) was obtained upon reaction of genetic material with HO radicals generated either by γ-radiolysis or Fenton-type reactions. Our results contributed to the debate in the literature regarding absolute level of lesions, method of HO radical generation, 5'/5' diastereomeric ratio in cPu, and relative abundance between cPu and 8-oxo-Pu.
Topics: Animals; DNA; DNA Damage; Humans; Hydrogen Peroxide; Hydroxyl Radical; Iron; Oligodeoxyribonucleotides; Purines
PubMed: 31717733
DOI: 10.3390/molecules24213860 -
Radiation Research Oct 2020FLASH radiotherapy delivers a high dose (≥10 Gy) at a high rate (≥40 Gy/s). In this way, particles are delivered in pulses as short as a few nanoseconds. At that...
FLASH radiotherapy delivers a high dose (≥10 Gy) at a high rate (≥40 Gy/s). In this way, particles are delivered in pulses as short as a few nanoseconds. At that rate, intertrack reactions between chemical species produced within the same pulse may affect the heterogeneous chemistry stage of water radiolysis. This stochastic process suits the capabilities of the Monte Carlo method, which can model intertrack effects to aid in radiobiology research, including the design and interpretation of experiments. In this work, the TOPAS-nBio Monte Carlo track-structure code was expanded to allow simulations of intertrack effects in the chemical stage of water radiolysis. Simulation of the behavior of radiolytic yields over a long period of time (up to 50 s) was verified by simulating radiolysis in a Fricke dosimeter irradiated by 60Co γ rays. In addition, LET-dependent G values of protons delivered in single squared pulses of widths, 1 ns, 1 µs and 10 µs, were obtained and compared to simulations using no intertrack considerations. The Fricke simulation for the calculated G value of Fe3+ ion at 50 s was within 0.4% of the accepted value from ICRU Report 34. For LET-dependent G values at the end of the chemical stage, intertrack effects were significant at LET values below 2 keV/µm. Above 2 keV/µm the reaction kinetics remained limited locally within each track and thus, effects of intertrack reactions remained low. Therefore, when track structure simulations are used to investigate the biological damage of FLASH irradiation, these intertrack reactions should be considered. The TOPAS-nBio framework with the expansion to intertrack chemistry simulation provides a useful tool to assist in this task.
Topics: Cobalt Radioisotopes; Computer Simulation; Electrons; Ferrous Compounds; Gamma Rays; Humans; Hydrogen-Ion Concentration; Linear Energy Transfer; Models, Biological; Monte Carlo Method; Phantoms, Imaging; Proton Therapy; Protons; Radiometry; Radiotherapy Dosage; Stochastic Processes; Sulfuric Acids
PubMed: 32857855
DOI: 10.1667/RADE-20-00084.1 -
International Journal of Molecular... Sep 2020We report the generation of gold nanoparticles (AuNPs) from the aqueous solution of chloro(2,2',2″-terpyridine)gold(III) ion ([Au(tpy)Cl]) through X-ray radiolysis and...
We report the generation of gold nanoparticles (AuNPs) from the aqueous solution of chloro(2,2',2″-terpyridine)gold(III) ion ([Au(tpy)Cl]) through X-ray radiolysis and optical excitation at a synchrotron. The original purpose of the experiment was to investigate the photoinduced structural changes of [Au(tpy)Cl] upon 400 nm excitation using time-resolved X-ray liquidography (TRXL). Initially, the TRXL data did not show any signal that would suggest structural changes of the solute molecule, but after an induction time, the TRXL data started to show sharp peaks and valleys. In the early phase, AuNPs with two types of morphology, dendrites, and spheres, were formed by the reducing action of hydrated electrons generated by the X-ray radiolysis of water, thereby allowing the detection of TRXL data due to the laser-induced lattice expansion and relaxation of AuNPs. Along with the lattice expansion, the dendritic and spherical AuNPs were transformed into smaller, raspberry-shaped AuNPs of a relatively uniform size via ablation by the optical femtosecond laser pulse used for the TRXL experiment. Density functional theory calculations confirm that the reduction potential of the metal complex relative to the hydration potential of X-ray-generated electrons determines the facile AuNP formation observed for [Au(tpy)Cl].
Topics: Electrons; Gold; Gold Compounds; Laser Therapy; Lasers; Metal Nanoparticles; Particle Size; Pulse Radiolysis; Solutions; Synchrotrons; Water; X-Ray Diffraction; X-Rays
PubMed: 32992497
DOI: 10.3390/ijms21197125 -
Chemical Science Sep 2021Conjugated molecular chains have the potential to act as "molecular wires" that can be employed in a variety of technologies, including catalysis, molecular electronics,...
Conjugated molecular chains have the potential to act as "molecular wires" that can be employed in a variety of technologies, including catalysis, molecular electronics, and quantum information technologies. Their successful application relies on a detailed understanding of the factors governing the electronic energy landscape and the dynamics of electrons in such molecules. We can gain insights into the energetics and dynamics of charges in conjugated molecules using time-resolved infrared (TRIR) detection combined with pulse radiolysis. Nitrile (C[triple bond, length as m-dash]N) bands can act as IR probes for charges, based on IR frequency shifts, because of their exquisite sensitivity to the degree of electron delocalization and induced electric field. Here, we show that the IR intensity and linewidth can also provide unique and complementary information on the nature of charges. Quantifications of IR intensity and linewidth in a series of nitrile-functionalized oligophenylenes reveal that the C[triple bond, length as m-dash]N vibration is coupled to the nuclear and electronic structural changes, which become more prominent when an excess charge is present. We synthesized a new series of ladder-type oligophenylenes that possess planar aromatic structures, as revealed by X-ray crystallography. Using these, we demonstrate that C[triple bond, length as m-dash]N vibrations can report charge fluctuations associated with nuclear movements, namely those driven by motions of flexible dihedral angles. This happens only when a charge has room to fluctuate in space.
PubMed: 34667576
DOI: 10.1039/d1sc03455c