-
Proceedings of the National Academy of... May 2023Protonation reactions involving organometallic complexes are ubiquitous in redox chemistry and often result in the generation of reactive metal hydrides. However, some...
Protonation reactions involving organometallic complexes are ubiquitous in redox chemistry and often result in the generation of reactive metal hydrides. However, some organometallic species supported by η-pentamethylcyclopentadienyl (Cp*) ligands have recently been shown to undergo ligand-centered protonation by direct proton transfer from acids or tautomerization of metal hydrides, resulting in the generation of complexes bearing the uncommon η-pentamethylcyclopentadiene (Cp*H) ligand. Here, time-resolved pulse radiolysis (PR) and stopped-flow spectroscopic studies have been applied to examine the kinetics and atomistic details involved in the elementary electron- and proton-transfer steps leading to complexes ligated by Cp*H, using Cp*Rh(bpy) as a molecular model (where bpy is 2,2'-bipyridyl). Stopped-flow measurements coupled with infrared and UV-visible detection reveal that the sole product of initial protonation of Cp*Rh(bpy) is [Cp*Rh(H)(bpy)], an elusive hydride complex that has been spectroscopically and kinetically characterized here. Tautomerization of the hydride leads to the clean formation of [(Cp*H)Rh(bpy)]. Variable-temperature and isotopic labeling experiments further confirm this assignment, providing experimental activation parameters and mechanistic insight into metal-mediated hydride-to-proton tautomerism. Spectroscopic monitoring of the second proton transfer event reveals that both the hydride and related Cp*H complex can be involved in further reactivity, showing that [(Cp*H)Rh] is not necessarily an off-cycle intermediate, but, instead, depending on the strength of the acid used to drive catalysis, an active participant in hydrogen evolution. Identification of the mechanistic roles of the protonated intermediates in the catalysis studied here could inform design of optimized catalytic systems supported by noninnocent cyclopentadienyl-type ligands.
PubMed: 37186841
DOI: 10.1073/pnas.2217189120 -
Molecules (Basel, Switzerland) Dec 2021One-electron oxidation of 2-selenouracil (2-SeU) by hydroxyl (OH) and azide (N) radicals leads to various primary reactive intermediates. Their optical absorption...
One-electron oxidation of 2-selenouracil (2-SeU) by hydroxyl (OH) and azide (N) radicals leads to various primary reactive intermediates. Their optical absorption spectra and kinetic characteristics were studied by pulse radiolysis with UV-vis spectrophotometric and conductivity detection and by the density functional theory (DFT) method. The transient absorption spectra recorded in the reactions of OH with 2-SeU are dominated by an absorption band with an λ = 440 nm, the intensity of which depends on the concentration of 2-SeU and pH. Based on the combination of conductometric and DFT studies, the transient absorption band observed both at low and high concentrations of 2-SeU was assigned to the dimeric 2c-3e Se-Se-bonded radical in neutral form (2). The dimeric radical (2) is formed in the reaction of a selenyl-type radical (6) with 2-SeU, and both radicals are in equilibrium with K = 1.3 × 10 M at pH 4 (below the pK of 2-SeU). Similar equilibrium with K = 4.4 × 10 M was determined for pH 10 (above the pK of 2-SeU), which admittedly involves the same radical (6) but with a dimeric 2c-3e Se-Se bonded radical in anionic form (2). In turn, at the lowest concentration of 2-SeU (0.05 mM) and pH 10, the transient absorption spectrum is dominated by an absorption band with an λ = 390 nm, which was assigned to the OH adduct to the double bond at C5 carbon atom (3) based on DFT calculations. Similar spectral and kinetic features were also observed during the N-induced oxidation of 2-SeU. In principle, our results mostly revealed similarities in one-electron oxidation pathways of 2-SeU and 2-thiouracil (2-TU). The major difference concerns the stability of dimeric radicals with a 2c-3e chalcogen-chalcogen bond in favor of 2-SeU.
Topics: Oxidation-Reduction; Pulse Radiolysis; Sulfur Compounds; Uracil; Water
PubMed: 35011366
DOI: 10.3390/molecules27010133 -
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 -
The Biochemical Journal Apr 19741. Detailed studies on the mechanism of the enzymic reaction of bovine superoxide dismutase were carried out by using pulse radiolysis and electron paramagnetic...
1. Detailed studies on the mechanism of the enzymic reaction of bovine superoxide dismutase were carried out by using pulse radiolysis and electron paramagnetic resonance (e.p.r.). 2. The second-order rate constant for reaction between superoxide dismutase and the superoxide ion was redetermined as (2.37+/-0.18)x10(9)m(-1).s(-1) at 25 degrees C. This reaction governs the turnover, and any first-order steps must have rate constants higher than about 10(6)s(-1). Turnover has a low activation energy and is slowed substantially when the viscosity is increased with glycerol, confirming that the reaction rate is near the limit for diffusion control. In water a reversible conformation change to a less active form appears to take place above about 40 degrees C. 3. Pre-steady-state rates of reduction and reoxidation of copper in the enzyme are consistent with these processes being rate-limiting in enzyme turnover. 4. Examination, with the help of computer simulation, of the e.p.r. spectra at 9 and 35GHz of native superoxide dismutase indicated that, apart from 10-20% of impurities, only one species of Cu(2+) is distinguishable. Further, the specific activity of our enzyme preparations, measured by pulse radiolysis, is at least as high as that obtained by other workers. 5. Nevertheless, measurement of the proportion of copper present as Cu(2+) (determined both optically and by e.p.r. spectroscopy) in the steady states approached from both the oxidized and the reduced forms of the enzyme, indicates (after allowing for the impurities) that only half of the copper atoms participate in turnover. E.p.r. spectroscopy provided no evidence for differences between functioning and non-functioning Cu(2+) atoms. 6. It is suggested that the results may be best interpreted in terms of an allosteric type of mechanism, with two initially indistinguishable copper atoms in the enzyme. Reaction of one of these with a superoxide ion then renders the other, at least transiently, unreactive.
Topics: Animals; Binding Sites; Cattle; Computers; Copper; Electron Spin Resonance Spectroscopy; Free Radicals; Freezing; Glycerol; Kinetics; Oscillometry; Oxidation-Reduction; Oxygen; Protein Binding; Protein Conformation; Radiochemistry; Superoxide Dismutase; Temperature; Thermodynamics; Time Factors
PubMed: 4377100
DOI: 10.1042/bj1390049 -
Molecules (Basel, Switzerland) Jan 2018Oxidation reactions by radicals constitute a very important class of chemical reactions in solution. Radiation Chemistry methods allow producing, in a controlled way,... (Review)
Review
Oxidation reactions by radicals constitute a very important class of chemical reactions in solution. Radiation Chemistry methods allow producing, in a controlled way, very reactive oxidizing radicals, such as OH, CO₃, NO₃, SO₄, and N₃. Although the radical cation of water, H₂O, with a very short lifetime (shorter than 1 ps) is the precursor of these radicals in aqueous solutions, its chemistry is usually known to be limited to the reaction of proton transfer by forming OH radical. Herein, we stress situations where H₂O undergoes electron transfer reaction in competition with proton transfer.
Topics: Cations; Electrons; Free Radicals; Kinetics; Oxidation-Reduction; Protons; Pulse Radiolysis; Solutions; Time Factors; Water
PubMed: 29373497
DOI: 10.3390/molecules23020244 -
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 -
The Biochemical Journal Jul 19691. Hydrated electrons produced by pulse radiolysis were used to study the interaction of polyanionic glycosaminoglycans and related compounds with the counterions...
1. Hydrated electrons produced by pulse radiolysis were used to study the interaction of polyanionic glycosaminoglycans and related compounds with the counterions Methylene Blue and cetylpyridinium chloride. 2. The effect of added salt (potassium chloride) on the interaction indicates that the relative binding affinities, with respect to the types of anionic site present, increases for both counterions in the order CO(2) (-)
pulse radiolysis when metachromasia is completely removed. Topics: Binding Sites; Electrons; Glycosaminoglycans; Methylene Blue; Potassium Chloride; Pyridinium Compounds; Spectrum Analysis; Staining and Labeling
PubMed: 4185242
DOI: 10.1042/bj1130465 -
International Journal of Molecular... Apr 2021Within the reactive oxygen species (ROS) generated by cellular metabolisms, hydroxyl radicals (HO) play an important role, being the most aggressive towards...
Within the reactive oxygen species (ROS) generated by cellular metabolisms, hydroxyl radicals (HO) play an important role, being the most aggressive towards biomolecules. The reactions of HO with methionine residues (Met) in peptides and proteins have been intensively studied, but some fundamental aspects remain unsolved. In the present study we examined the biomimetic model made of Ac-Met-OMe, as the simplest model peptide backbone, and of HO generated by ionizing radiation in aqueous solutions under anoxic conditions. We performed the identification and quantification of transient species by pulse radiolysis and of final products by LC-MS and high-resolution MS/MS after γ-radiolysis. By parallel photochemical experiments, using 3-carboxybenzophenone (CB) triplet with the model peptide, we compared the outcomes in terms of short-lived intermediates and stable product identification. The result is a detailed mechanistic scheme of Met oxidation by HO, and by CB triplets allowed for assigning transient species to the pathways of products formation.
Topics: Gamma Rays; Hydroxyl Radical; Methionine; Oxidation-Reduction; Peptides; Photolysis; Pulse Radiolysis
PubMed: 33946289
DOI: 10.3390/ijms22094773 -
Pharmaceutics Nov 2022Nanoparticle-based drug delivery systems (DDS) have been developed as effective diagnostic and low-dose imaging agents. Nano-imaging agents with particles greater than...
Nanoparticle-based drug delivery systems (DDS) have been developed as effective diagnostic and low-dose imaging agents. Nano-imaging agents with particles greater than 100 nm are difficult to accumulate in pancreatic cancer cells, making high-intensity imaging of pancreatic cancer challenging. Peptides composed of histidine and glycine were designed and synthesized. Additionally, aqueous peptide solutions were irradiated with γ-rays to produce peptide nanogels with an average size of 25-53 nm. The mechanisms underlying radiation-mediated peptide crosslinking were investigated by simulating peptide particle formation based on rate constants. The rate constants for reactions between peptides and reactive species produced by water radiolysis were measured using pulse radiolysis. HGGGHGGGH (H9, H-histidine; G-glycine) particles exhibited a smaller size, as well as high formation yield, stability, and biodegradability. These particles were labeled with fluorescent dye to change their negative surface potential and enhance their accumulation in pancreatic cancer cells. Fluorescent-labeled H9 particles accumulated in PANC1 human pancreatic cancer cells, demonstrating that these particles are effective nano-imaging agents for intractable cancers.
PubMed: 36365217
DOI: 10.3390/pharmaceutics14112400 -
Antioxidants (Basel, Switzerland) Jun 2023The successive steps of the oxidation mechanism of crocin, a major compound of saffron, by the free OH radical are investigated by pulse radiolysis, steady-state (gamma)...
The successive steps of the oxidation mechanism of crocin, a major compound of saffron, by the free OH radical are investigated by pulse radiolysis, steady-state (gamma) radiolysis methods, and molecular simulations. The optical absorption properties of the transient species and their reaction rate constants are determined. The absorption spectrum of the oxidized radical of crocin resulting from the H-abstraction presents a maximum of 678 nm and a band of 441 nm, almost as intense as that of crocin. The spectrum of the covalent dimer of this radical contains an intense band at 441 nm and a weaker band at 330 nm. The final oxidized crocin, issued from radical disproportionation, absorbs weaker with a maximum of 330 nm. The molecular simulation results suggest that the OH radical is electrostatically attracted by the terminal sugar and is scavenged predominantly by the neighbor methyl site of the polyene chain as in a mechanism. Based on detailed experimental and theoretical investigations, the antioxidant properties of crocin are highlighted.
PubMed: 37371932
DOI: 10.3390/antiox12061202