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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 Journal of Physical Chemistry. A Jan 2023Transient chemistry of sensitizing dyes is important to obtain insights into the photochemical conversion processes of light harvesting assemblies. We have now employed...
Transient chemistry of sensitizing dyes is important to obtain insights into the photochemical conversion processes of light harvesting assemblies. We have now employed transient absorption spectroscopy (pulsed laser and pulse radiolysis) to characterize the excited state and radical intermediates of a perylene derivative, (5,10,15,20-Tetraphenylbisbenz[5,6]indeno[1,2,3-:1',2',3'-]perylene (DBP). The distinguishable transient absorption features for the singlet and triplet excited states and radical anion and radical cation provide spectral fingerprints to identify the reaction intermediates in photochemical energy and electron transfer processes of composite systems involving DBP. For example, identifying these transients in the energy transfer processes of the rubrene-DBP system would aid in establishing their role as annihilator-emitter for triplet-triplet annihilation up-conversion (TTA-UC). The transient characterization thus serves as an important mechanistic fingerprint for elucidating mechanistic details of systems employing DBP in optoelectronic applications.
PubMed: 36375093
DOI: 10.1021/acs.jpca.2c06904 -
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 -
ACS Omega Nov 2022Pulse radiolysis with a custom multichannel detection system has been used to measure the kinetics of the radiation chemistry reactions of aqueous solutions of...
Pulse radiolysis with a custom multichannel detection system has been used to measure the kinetics of the radiation chemistry reactions of aqueous solutions of chromium(VI) to 325 °C for the first time. Kinetic traces were measured simultaneously over a range of wavelengths and fit to obtain the associated high-temperature rate coefficients and Arrhenius parameters for the reactions of Cr(VI) + , Cr(VI) + H, and Cr(V) + OH. These kinetic parameters can be used to predict the behavior of toxic Cr(VI) in models of aqueous systems for applications in nuclear technology, industrial wastewater treatment, and chemical dosimetry.
PubMed: 36340103
DOI: 10.1021/acsomega.2c04807 -
Journal of Inorganic Biochemistry Jan 2023Nitric oxide synthase (NOS) is a cytochrome P450-type mono‑oxygenase that catalyzes the oxidation of L-arginine to nitric oxide. We previously observed that...
Intramolecular electron transfer from biopterin to Fe-O complex in nitric oxide synthases occurs at very different rates between bacterial and mammalian enzymes: Direct observation of a catalytically active intermediate.
Nitric oxide synthase (NOS) is a cytochrome P450-type mono‑oxygenase that catalyzes the oxidation of L-arginine to nitric oxide. We previously observed that intramolecular electron transfer from biopterin to Fe-O in Deinococcus radiodurans NOS (DrNOS) using pulse radiolysis. However, the rate of electron transfer in DrNOS (2.2 × 10 s) contrasts with a reported corresponding rate (11 s) in a mammalian NOS determined using rapid freeze-quench (RFQ) EPR. We applied pulse radiolysis to Bacillus subtilis NOS (bsNOS) and to rat neural NOS oxygenase domain NOS (mNOS). Concurrently, RFQ EPR was used to trap a pterin radical during single-turnover enzyme reactions of the enzymes. By using the pulse radiolysis method, hydrated electrons (e) reduced the heme iron of NOS enzymes. Subsequently, ferrous heme reacted with O to form a Fe-O intermediate. In the presence of pterin, the intermediate of bsNOS was found to convert to other intermediate in the time range of milliseconds. A similar process was determined to have occurred after pulse radiolysis of the pterin-bound mNOS, though the rate was much slower. The intermediates of all of the NOS enzymes further converted to the original ferric form in the time range of seconds. When using the RFQ method, pterin radicals were formed very rapidly in both DrNOS and bsNOS in the time range of milliseconds. In contrast, the pterin radical in mNOS was observed to form slowly, at a rate of ∼20 s.
Topics: Animals; Rats; Arginine; Biopterins; Electrons; Ferrous Compounds; Heme; Iron; Nitric Oxide; Nitric Oxide Synthase; Oxidation-Reduction; Pterins; Bacillus subtilis
PubMed: 36327499
DOI: 10.1016/j.jinorgbio.2022.112035 -
Physical Chemistry Chemical Physics :... Aug 2022Reactivity of transients involving Zn in high-temperature water radiolysis has been studied in the temperature range of 25-300 °C. The reduced monovalent zinc species...
Reactivity of transients involving Zn in high-temperature water radiolysis has been studied in the temperature range of 25-300 °C. The reduced monovalent zinc species were generated from an electron transfer process between the hydrated electron and Zn ions using pulse radiolysis. The Zn species can subsequently be oxidized by the radiolytically-produced oxidizing species: ˙OH, HO and ˙H. We find that the absorption of monovalent zinc is very sensitive to the pH of the medium. An absorption maximum at 306-311 nm is most pronounced at pH 7 and the signal then decreases in acidic media where the reducing electrons are competitively captured by protons. At pH values higher than 7, hydroxo-forms of Zn are created and the maximum of the absorption signal begins to shift to the red spectral region. We find that the optical spectrum of Zn cannot be fully explained in terms of a charge-transfer to solvent (CTTS) process, which was previously proposed. Reaction rates of most of the recombination reactions investigated follow the empirical Arrhenius relationship at temperatures up to 200 °C and have been determined at higher temperatures for the first time. A bimolecular disproportionation reaction of Zn is not observed under the conditions investigated.
PubMed: 35959849
DOI: 10.1039/d2cp02434a -
International Journal of Molecular... Jul 2022The use of spectroscopic techniques has shown that human serum albumin (HSA) undergoes reversible self-aggregation through protein−protein interactions. It ensures the...
The use of spectroscopic techniques has shown that human serum albumin (HSA) undergoes reversible self-aggregation through protein−protein interactions. It ensures the subsequent overlapping of electron clouds along with the stiffening of the conformation of the interpenetrating network of amino acids of adjacent HSA molecules. The HSA oxidation process related to the transfer of one electron was investigated by pulse radiolysis and photochemical methods. It has been shown that the irradiation of HSA solutions under oxidative stress conditions results in the formation of stable protein aggregates. The HSA aggregates induced by ionizing radiation are characterized by specific fluorescence compared to the emission of non-irradiated solutions. We assume that HSA dimers are mainly responsible for the new emission. Dityrosine produced by the intermolecular recombination of protein tyrosine radicals as a result of radiolysis of an aqueous solution of the protein is the main cause of HSA aggregation by cross-linking. Analysis of the oxidation process of HSA confirmed that the reaction of mild oxidants (Br2•−, N3•, SO4•−) with albumin leads to the formation of covalent bonds between tyrosine residues. In the case of •OH radicals and partly, Cl2•−, species other than DT are formed. The light emission of this species is similar to the emission of self-associated HSA.
Topics: Fluorescent Dyes; Humans; Oxidation-Reduction; Radiation, Ionizing; Serum Albumin, Human; Tyrosine
PubMed: 35897662
DOI: 10.3390/ijms23158090 -
Heliyon Jul 2022Natural dietary products of health promoting and disease preventive functional relevance are gaining significant prominence. Current investigation was aimed to decipher...
Natural dietary products of health promoting and disease preventive functional relevance are gaining significant prominence. Current investigation was aimed to decipher the underlying molecular mechanism responsible for the antimutagenic action contributing to functional relevance of floral honey ('', Karanj honey) derived abscisic acid (ABA) against ethyl methanesulfonate (EMS) induced mutagenesis. Differential expression of proteins under different treatment conditions was ascertained by 2D gel electrophoresis. Selectively up-regulated characterized using MALDI-TOF MS/MS were identified as polyribonucleotide nucleotidyl transferse (PNPase), LPS-assembly lipoprotein (LptE), Outer membrane Usher protein (HtrE), ATP-dependent DNA helicase (RecG), and Phosphomethyl pyrimidine synthase (ThiC). Antimutagenicity exerted by ABA against EMS was ∼78% in wild type MG1655 strain however, in , this activity was found to be ∼60, 10, 9 and 10%, respectively. Proteomic analysis and antimutagenicity studies using single gene knockout strains thus indicated about the possible role of in observed antimutagenicity. Cyclic voltametry as well as competition kinetics through pulse radiolysis confirmed lack of antioxidant capacity in abscisic acid apparently ruling out the possibility of scavenging of electrophilic intermediates generated by ethyl methanesulfonate. It is proposed that ABA is exerting antimutagenicity through its involvement at the cellular level leading to physiological adaptation, strengthening of cell wall proteins and up-regulation of the repair proteins. This study provides a novel dimension to the functional role of abscisic acid from its nutraceutical perspective.
PubMed: 35874072
DOI: 10.1016/j.heliyon.2022.e09945 -
Physical Chemistry Chemical Physics :... Oct 2022Molten chloride salts are currently under consideration as combined coolant and liquid fuel for next-generation molten salt nuclear reactors. Unlike complementary...
Molten chloride salts are currently under consideration as combined coolant and liquid fuel for next-generation molten salt nuclear reactors. Unlike complementary light-water reactor technologies, the radiation science underpinning molten salts is in its infancy, and thus requires a fundamental mechanistic investigation to elucidate the radiation-driven chemistry within molten salt reactors. Here we present an electron pulse radiolysis kinetics study into the behaviour of the primary radiolytic species generated in molten chloride systems, , the solvated electron (e) and di-chlorine radical anion (Cl˙). We examine the reaction of e with Zn from 400-600 °C ( = 30.31 ± 0.09 kJ mol), and the kinetics and decay mechanisms of Cl˙ in molten lithium chloride-potassium chloride (LiCl-KCl) eutectic. In the absence of Zn, the lifetime of e was found to be dictated by residual impurities in ostensibly "pure" salts, and thus the observed decay is dependent on sample history rather than being an intrinsic property of the salt. The decay of Cl˙ is complex, owing to the competition of Cl˙ disproportionation with several other chemical pathways, one of which involves reduction by radiolytically-produced Zn species. Overall, the reported findings demonstrate the richness and complexity of chemistry involving the interactions of ionizing radiation with molten salts.
PubMed: 35789354
DOI: 10.1039/d2cp01194h -
International Journal of Molecular... Jun 2022Hydroxyl radicals (HO) have long been regarded as a major source of cellular damage. The reaction of HO with methionine residues (Met) in peptides and proteins is a...
Hydroxyl radicals (HO) have long been regarded as a major source of cellular damage. The reaction of HO with methionine residues (Met) in peptides and proteins is a complex multistep process. Although the reaction mechanism has been intensively studied, some essential parts remain unsolved. In the present study we examined the reaction of HO generated by ionizing radiation in aqueous solutions under anoxic conditions with two compounds representing the simplest model peptide backbone CHC(O)NHCHXC(O)NHCH, where X = CHCHSCH or CHSCH, i.e., the Met derivative in comparison with the cysteine-methylated derivative. We performed the identification and quantification of transient species by pulse radiolysis and final products by LC-MS and high-resolution MS/MS after γ-radiolysis. The results allowed us to draw for each compound a mechanistic scheme. The fate of the initial one-electron oxidation at the sulfur atom depends on its distance from the peptide backbone and involves transient species of five-membered and/or six-membered ring formations with different heteroatoms present in the backbone as well as quite different rates of deprotonation in forming α-(alkylthio)alkyl radicals.
Topics: Cysteine; Hydroxyl Radical; Methionine; Oxidation-Reduction; Peptides; Pulse Radiolysis; Sulfides; Tandem Mass Spectrometry
PubMed: 35742994
DOI: 10.3390/ijms23126550