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Molecules (Basel, Switzerland) Sep 2021The conversion of ribonucleosides to 2'-deoxyribonucleosides is catalyzed by ribonucleoside reductase enzymes in nature. One of the key steps in this complex radical...
The conversion of ribonucleosides to 2'-deoxyribonucleosides is catalyzed by ribonucleoside reductase enzymes in nature. One of the key steps in this complex radical mechanism is the reduction of the 3'-ketodeoxynucleotide by a pair of cysteine residues, providing the electrons via a disulfide radical anion (RSSR) in the active site of the enzyme. In the present study, the bioinspired conversion of ketones to corresponding alcohols was achieved by the intermediacy of disulfide radical anion of cysteine (CysSSCys) in water. High concentration of cysteine and pH 10.6 are necessary for high-yielding reactions. The photoinitiated radical chain reaction includes the one-electron reduction of carbonyl moiety by disulfide radical anion, protonation of the resulting ketyl radical anion by water, and H-atom abstraction from CysSH. The (CysSSCys) transient species generated by ionizing radiation in aqueous solutions allowed the measurement of kinetic data with ketones by pulse radiolysis. By measuring the rate of the decay of (CysSSCys) at λ = 420 nm at various concentrations of ketones, we found the rate constants of three cyclic ketones to be in the range of 10-10 Ms at ~22 °C.
Topics: Biomimetics; Disulfides; Hydroxyl Radical; Ketones; Kinetics; Water
PubMed: 34576900
DOI: 10.3390/molecules26185429 -
Molecules (Basel, Switzerland) Aug 2019Radiosensitizing properties of substituted uridines are of great importance for radiotherapy. Very recently, we confirmed 5-iodo-4-thio-2'-deoxyuridine (ISdU) as an...
Radiosensitizing properties of substituted uridines are of great importance for radiotherapy. Very recently, we confirmed 5-iodo-4-thio-2'-deoxyuridine (ISdU) as an efficient agent, increasing the extent of tumor cell killing with ionizing radiation. To our surprise, a similar derivative of 4-thio-2'-deoxyuridine, 5-bromo-4-thio-2'-deoxyuridine (BrSdU), does not show radiosensitizing properties at all. In order to explain this remarkable difference, we carried out a radiolytic (stationary and pulse) and quantum chemical studies, which allowed the pathways to all radioproducts to be rationalized. In contrast to ISdU solutions, where radiolysis leads to 4-thio-2'-deoxyuridine and its dimer, no dissociative electron attachment (DEA) products were observed for BrSdU. This observation seems to explain the lack of radiosensitizing properties of BrSdU since the efficient formation of the uridine-5-yl radical, induced by electron attachment to the modified nucleoside, is suggested to be an indispensable attribute of radiosensitizing uridines. A larger activation barrier for DEA in BrSdU, as compared to ISdU, is probably responsible for the closure of DEA channel in the former system. Indeed, besides DEA, the XSdU anions may undergo competitive protonation, which makes the release of X kinetically forbidden.
Topics: Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Chromatography, Liquid; Halogens; Histones; Humans; Models, Molecular; Molecular Conformation; Molecular Structure; Radiation-Sensitizing Agents; Tandem Mass Spectrometry; Thiouridine
PubMed: 31382376
DOI: 10.3390/molecules24152819 -
Journal of the American Chemical Society Aug 2021Graphene liquid cell transmission electron microscopy (TEM) has enabled the observation of a variety of nanoscale transformations. Yet understanding the chemistry of the...
Elucidating the Role of Halides and Iron during Radiolysis-Driven Oxidative Etching of Gold Nanocrystals Using Liquid Cell Transmission Electron Microscopy and Pulse Radiolysis.
Graphene liquid cell transmission electron microscopy (TEM) has enabled the observation of a variety of nanoscale transformations. Yet understanding the chemistry of the liquid cell solution and its impact on the observed transformations remains an important step toward translating insights from liquid cell TEM to benchtop chemistry. Gold nanocrystal etching can be used as a model system to probe the reactivity of the solution. FeCl has been widely used to promote gold oxidation in bulk and liquid cell TEM studies, but the roles of the halide and iron species have not been fully elucidated. In this work, we observed the etching trajectories of gold nanocrystals in different iron halide solutions. We observed an increase in gold nanocrystal etch rate going from Cl- to Br- to I-containing solutions. This is consistent with a mechanism in which the dominant role of halides is as complexation agents for oxidized gold species. Additionally, the mechanism through which FeCl induces etching in liquid cell TEM remains unclear. Ground-state bleaching of the Fe(III) absorption band observed through pulse radiolysis indicates that iron may react with Cl· radicals to form an oxidized transient species under irradiation. Complete active space self-consistent field (CASSCF) calculations indicate that the FeCl complex is oxidized to an Fe species with an OH radical ligand. Together our data indicate that an oxidized Fe species may be the active oxidant, while halides modulate the etch rate by tuning the reduction potential of gold nanocrystals.
PubMed: 34292703
DOI: 10.1021/jacs.1c05099 -
Dalton Transactions (Cambridge, England... Jun 2024First-of-a-kind temperature-controlled electron pulse radiolysis experiments facilitated the radiation-induced formation of Am(IV) in concentrated (6.0 M) HNO, and...
First-of-a-kind temperature-controlled electron pulse radiolysis experiments facilitated the radiation-induced formation of Am(IV) in concentrated (6.0 M) HNO, and enabled the derivation of Arrhenius and Eyring activation parameters for instigating the radical reaction between NO˙ and Am(III).
PubMed: 38776119
DOI: 10.1039/d4dt00991f -
Environmental Science & Technology May 2023Advanced reduction processes (ARP) have garnered increasing attention for the treatment of recalcitrant chemical contaminants, most notably per- and polyfluoroalkyl...
Advanced reduction processes (ARP) have garnered increasing attention for the treatment of recalcitrant chemical contaminants, most notably per- and polyfluoroalkyl substances (PFAS). However, the impact of dissolved organic matter (DOM) on the availability of the hydrated electron (e), the key reactive species formed in ARP, is not completely understood. Using electron pulse radiolysis and transient absorption spectroscopy, we measured bimolecular reaction rates constant for e reaction with eight aquatic and terrestrial humic substance and natural organic matter isolates ( ), with the resulting values ranging from (0.51 ± 0.01) to (2.11 ± 0.04) × 10 M s. measurements at varying temperature, pH, and ionic strength indicate that activation energies for diverse DOM isolates are ≈18 kJ mol and that could be expected to vary by less than a factor of 1.5 between pH 5 and 9 or from an ionic strength of 0.02 to 0.12 M. exhibited a significant, positive correlation to % carbonyl carbon for the isolates studied, but relationships to other DOM physicochemical properties were surprisingly more scattered. A 24 h UV/sulfite experiment employing chloroacetate as an e probe revealed that continued e exposure abates DOM chromophores and e scavenging capacity over a several hour time scale. Overall, these results indicate that DOM is an important e scavenger that will reduce the rate of target contaminant degradation in ARP. These impacts are likely greater in waste streams like membrane concentrates, spent ion exchange resins, or regeneration brines that have elevated DOM concentrations.
Topics: Dissolved Organic Matter; Water; Electrons; Water Pollutants, Chemical; Humic Substances
PubMed: 37141499
DOI: 10.1021/acs.est.3c00909 -
Radiation Physics and Chemistry... May 2023Hydroxychloroquine (HCQ) is a potential drug molecule for treating malaria. Recently it has also been tried as adjustment in Covid 19 therapy. Interaction of HCQ with...
Hydroxychloroquine (HCQ) is a potential drug molecule for treating malaria. Recently it has also been tried as adjustment in Covid 19 therapy. Interaction of HCQ with free radicals is very important, which controls its stability in the environment where free radicals are generated unintentionally. In this report, we present detailed investigation on the reactions of hydrated electrons (e ) and hydroxyl radical (OH) with HCQ in aqueous solution through electron pulse radiolysis technique and computational studies. The degradation of HCQ was found to be faster in the case of reaction with OH radicals. However, the degradation could be substantially slowed down in the presence of antioxidants like ascorbic acid and gallic acid. This revealed that the stability of HCQ could be enhanced in an oxidative environment in the presence of these two compounds, which are easily available through food supplements. Various global and local reactivity parameters are also determined to understand the reactivity trend using Hard-Soft Acid-Base (HSAB) principle in the realm of the DFT methods. Computational studies were performed to elucidate the site-specific reactivity trend towards the electrophilic and nucleophilic attack by calculating the condensed Fukui index for various species of HCQ.
PubMed: 36685709
DOI: 10.1016/j.radphyschem.2023.110785 -
ChemSusChem Nov 2023The use of hydrocarbon-based proton conducting membranes in fuel cells is currently hampered by the insufficient durability of the material in the device. Membrane aging...
The use of hydrocarbon-based proton conducting membranes in fuel cells is currently hampered by the insufficient durability of the material in the device. Membrane aging is triggered by the presence of reactive intermediates, such as HO⋅, which attack the polymer and eventually lead to chain breakdown and membrane failure. An adequate antioxidant strategy tailored towards hydrocarbon-based ionomers is therefore imperative to improve membrane lifetime. In this work, we perform studies on reaction kinetics using pulse radiolysis and γ-radiolysis as well as fuel cell experiments to demonstrate the feasibility of increasing the stability of hydrocarbon-based membranes against oxidative attack by implementing a Nature-inspired antioxidant strategy. We found that metalated-porphyrins are suitable for damage transfer and can be used in the fuel cell membrane to reduce membrane aging with a low impact on fuel cell performance.
PubMed: 37551734
DOI: 10.1002/cssc.202300775 -
Journal of the American Chemical Society Nov 2022While heteroatom-centered radicals are understood to be highly electrophilic, their ability to serve as transient electron-withdrawing groups and facilitate polar...
While heteroatom-centered radicals are understood to be highly electrophilic, their ability to serve as transient electron-withdrawing groups and facilitate polar reactions at distal sites has not been extensively developed. Here, we report a new strategy for the electronic activation of halophenols, wherein generation of a phenoxyl radical via formal homolysis of the aryl O-H bond enables direct nucleophilic aromatic substitution of the halide with carboxylate nucleophiles under mild conditions. Pulse radiolysis and transient absorption studies reveal that the neutral oxygen radical (O) is indeed an extraordinarily strong electron-withdrawing group [σ(O) = 2.79 vs σ(NO) = 1.27]. Additional mechanistic and computational studies indicate that the key phenoxyl intermediate serves as an open-shell electron-withdrawing group in these reactions, lowering the barrier for nucleophilic substitution by more than 20 kcal/mol relative to the closed-shell phenol form of the substrate. By using radicals as transient activating groups, this homolysis-enabled electronic activation strategy provides a powerful platform to expand the scope of nucleophile-electrophile couplings and enable previously challenging transformations.
Topics: Electrons; Electronics; Carboxylic Acids; Phenol; Reactive Oxygen Species
PubMed: 36395367
DOI: 10.1021/jacs.2c10296 -
Medical Physics Feb 2020Radiosensitizer enhanced radiotherapy provides the possibility of improved treatment outcomes by preferentially increasing the effectiveness of radiation within the...
Gold nanoparticle enhanced proton therapy: A Monte Carlo simulation of the effects of proton energy, nanoparticle size, coating material, and coating thickness on dose and radiolysis yield.
PURPOSE
Radiosensitizer enhanced radiotherapy provides the possibility of improved treatment outcomes by preferentially increasing the effectiveness of radiation within the tumor. Proton therapy offers improved sparing of tissue distal of the tumor along the beam path and reduced integral dose compared to conventional photon therapy. The combination of proton therapy with radiosensitizers offers the potential for an enhanced therapy with increased effect within the tumor and low integral dose. The simulations performed in this work determine the effect of nanoparticle characteristics and proton energy on the nanoscale dose and radiolysis yield enhancement for a single gold nanoparticle irradiated with a proton beam. This data can be used to determine optimal nanoparticle characteristics to enhance proton therapy.
METHODS
A two-stage Monte Carlo simulation was performed using Geant4. In the first stage of the simulation, the physical interactions of protons within a gold nanoparticle were modeled and the secondary electrons escaping the nanoparticle's surface were scored in a phase space file. In the second stage of the simulation, the phase space file was used as an input to model the physical interactions of the secondary electrons in water and the resulting production and chemical interactions of reactive species. By comparing a gold nanoparticle with an equivalent water nanoparticle, the nanoscale enhancement of dose and radiolysis yield was calculated.
RESULTS
A large nanoscale enhancement of both the dose and radiolysis yield of up to a factor of 11 due to gold nanoparticles was found for most simulated conditions. For 50 nm gold nanoparticles, a large enhancement factor of 9-11 was observed for high proton energies; however, the enhancement was reduced for proton energies below 10 MeV. For 5 MeV incident protons, it was found that the enhancement factor was approximately 9 for gold nanoparticles of sizes 5-25 nm with a reduction in enhancement observed for nanoparticle sizes outside this range. Additionally, it was found that larger nanoparticle sizes resulted in greater total energy deposition and radiolysis yields per proton flux but with reduced efficiency per nanoparticle mass. It was observed that a large loss of enhancement occurred for thick nanoparticle coatings. However, for polyethylene glycol (PEG) coatings, coating density had a minimal effect on enhancement.
CONCLUSIONS
A large enhancement in dose and radiolysis yield was observed. However, the low-energy secondary electrons produced within the gold for lower energy protons are susceptible to self-absorption and result in the loss of enhancement observed for larger nanoparticles and thicker coatings. The radiolysis yield and dose increase with nanoparticle size; however, the yield and dose per gold mass decrease due to self-absorption. Therefore, an intermediate nanoparticle size of approximately 10-25 nm maximizes both the radiolysis yield and dose as well as the enhancement. Coatings should be kept to the minimum effective thickness to limit the loss of enhancement. For molecular coatings such as PEG, coating density should be maximized as this increases the coating's effectiveness with only a minimal effect on enhancement.
Topics: Gold; Linear Energy Transfer; Metal Nanoparticles; Particle Size; Polyethylene Glycols; Proton Therapy; Pulse Radiolysis; Radiation Dosage; Radiotherapy Dosage; Silicon Dioxide
PubMed: 31725910
DOI: 10.1002/mp.13923 -
The Journal of Physical Chemistry. B Jan 2022This work shows that S atom substitution in phosphate controls the directionality of hole transfer processes between the base and sugar-phosphate backbone in DNA...
This work shows that S atom substitution in phosphate controls the directionality of hole transfer processes between the base and sugar-phosphate backbone in DNA systems. The investigation combines synthesis, electron spin resonance (ESR) studies in supercooled homogeneous solution, pulse radiolysis in aqueous solution at ambient temperature, and density functional theory (DFT) calculations of in-house synthesized model compound dimethylphosphorothioate (DMTP(O)═S) and nucleotide (5'--methoxyphosphorothioyl-2'-deoxyguanosine (G-P(O)═S)). ESR investigations show that DMTP(O)═S reacts with Cl to form the σσ* adduct radical -P-S[Formula: see text]Cl, which subsequently reacts with DMTP(O)═S to produce [-P-S[Formula: see text]S-P-]. -P-S[Formula: see text]Cl in G-P(O)═S undergoes hole transfer to Gua, forming the cation radical (G) via thermally activated hopping. However, pulse radiolysis measurements show that DMTP(O)═S forms the thiyl radical (-P-S) by one-electron oxidation, which did not produce [-P-S[Formula: see text]S-P-]. Gua in G-P(O)═S is oxidized unimolecularly by the -P-S intermediate in the sub-picosecond range. DFT thermochemical calculations explain the differences in ESR and pulse radiolysis results obtained at different temperatures.
Topics: DNA; Phosphates; Pulse Radiolysis; Sugars; Sulfur
PubMed: 34990129
DOI: 10.1021/acs.jpcb.1c09068