Production Of Radical Intermediates Research Articles

Detection of Few Hydrogen Peroxide Molecules Using Self-Reporting Fluorescent Nanodiamond Quantum Sensors

Hydrogen peroxide (H2O2) plays an important role in various signal transduction pathways and regulates important cellular processes. However, monitoring and quantitatively assessing the distribution of H2O2 molecules inside living cells requires a nanoscale sensor with molecular-level sensitivity. Herein, we show the first demonstration of sub-10 nm-sized fluorescent nanodiamonds (NDs) as catalysts for the decomposition of H2O2 and the production of radical intermediates at the nanoscale. Furthermore, the nitrogen-vacancy quantum sensors inside the NDs are employed to quantify the aforementioned radicals. We believe that our method of combining the peroxidase-mimicking activities of the NDs with their intrinsic quantum sensor showcases their application as self-reporting H2O2 sensors with molecular-level sensitivity and nanoscale spatial resolution. Given the robustness and the specificity of the sensor, our results promise a new platform for elucidating the role of H2O2 at the cellular level.

Visible Light Photoredox Activation of Sulfonyl Chlorides: Applications in Organic Synthesis

AbstractSince the seminal studies from the groups of MacMillan, Stephenson and Yoon, visible light (400‐700 nm) photoredox catalysis has been established as a powerful strategy to facilitate activation of organic molecules and invention of novel synthetic methodologies. Indeed, recent days, this protocol enables the syntheses of diversely functionalized organic molecules such as coerulescines, pseudotabersonines, drugs, agro chemicals, etc. Generally, activation of the redox‐active functional groups of the radical precursors including diazonium salts, iodoniumsalts, sulfoniumsalts, phosphate esters, amines and sulfonyl chlorides is achieved via single‐electron transfer from a photocatalyst excited by visible light irradiation sources. To date, some important reviews are available that summarize the visible light photoredox catalyses of various classes of organic compounds. To the best of our knowledge, however, there is still no review article exclusively discourses about the visible light induced productions and applications of radical species of sulfonyl chlorides (AASO2Cl, AA=alkyl/aryl). Therefore, in this review, we provide an overview on the visible light assisted procedures employed for the production of radical intermediates from sulfonyl chlorides. In addition, here we account the applications of these radical species in the syntheses of bi(hetero)aryls, difluoromethyl lactones, difluoromethyl pyrrolidines, polycyclic aromatic compounds, sulfones, trifluoromethyl (hetero)aryls, α‐trifluoromethyl ketones and so on.

Catching a radical in action

Metalloproteins Many enzymes catalyze reactions through the production of radical intermediates. Radical SAM enzymes, the largest superfamily of enzymes in nature, do this by using an iron-sulfur cluster to cleave S-adenosylmethionine and produce a radical intermediate. Using freeze quenching, Horitani et al. were able to trap a previously unseen radical intermediate from bacterial pyruvate formate-lyase activating enzyme. Spectroscopy revealed that the intermediate consists of a short-lived covalent bond between the terminal carbon of 5′-deoxyadenosyl and the single iron atom of the iron-sulfur cluster. Not only does the observation of this radical expand our mechanistic understanding of radical SAM enzymes, but it expands the range of enzyme active sites or cofactors that function through an organometallic center. Science , this issue p. [822][1] [1]: /lookup/doi/10.1126/science.aaf5327

Radical SAM catalysis via an organometallic intermediate with an Fe-[5'-C]-deoxyadenosyl bond.

Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to cleave SAM to initiate diverse radical reactions. These reactions are thought to involve the 5'-deoxyadenosyl radical intermediate, which has not yet been detected. We used rapid freeze-quenching to trap a catalytically competent intermediate in the reaction catalyzed by the radical SAM enzyme pyruvate formate-lyase activating enzyme. Characterization of the intermediate by electron paramagnetic resonance and (13)C, (57)Fe electron nuclear double-resonance spectroscopies reveals that it contains an organometallic center in which the 5' carbon of a SAM-derived deoxyadenosyl moiety forms a bond with the unique iron site of the [4Fe-4S] cluster. Discovery of this intermediate extends the list of enzymatic bioorganometallic centers to the radical SAM enzymes, the largest enzyme superfamily known, and reveals intriguing parallels to B12 radical enzymes.

Photolysis of diaryliodonium salts (UV/Vis, EPR and GC/MS investigations)

The photodecomposition of commercial lipophilic diaryliodonium hexafluoroantimonate SarCat ® SR-1012 was investigated in acetonitrile (ACN) and ACN/H 2O mixed solvents by means of UV/Vis spectroscopy, an EPR in situ spin trapping technique and GC/MS analysis. The application of the spin traps nitrosodurene (ND) and 5,5-dimethyl-1-pyrroline N-oxide gave evidence for the production of radical intermediates corresponding to the breaking of the carbon–iodine bond, in addition to carbon–oxygen bonds in SR-1012 aryl substitution. The photolytic products analyzed in aprotic acetonitrile were iodobenzene, acetanilide, biphenyl and C 12H 25CH(OH)CH 3, while in ACN/H 2O (1:1, vol.) solution iodobenzene, biphenyl, C 12H 25CH(OH)CH 2OC 6H 4OH and hydroxylated biphenyls were identified. The influence of oxygen on the product distribution in both solvent systems was inconsequential. The proton concentrations photogenerated in the irradiated SR-1012 ACN/H 2O solutions were quantified spectrophotometrically using bromophenol blue indicator.

EPR study of spin-trapped free radical intermediates formed in the heterogeneously-assisted photodecomposition of acetaldehyde †

Electron paramagnetic resonance spectroscopy is used to detect radical adducts of PBN (α-phenyl N-tert-butyl nitrone) generated by exposure of solutions and suspensions to ambient or high power UV at 300 K. Exposure of acetaldehyde to direct sunlight generates a different PBN radical adduct to high power UV irradiation. Direct sunlight irradiation of deoxygenated acetaldehyde generates PBN–acetyl adducts whereas direct sunlight exposure of oxygenated acetaldehyde produces PBN–acetoxyl adducts. High power UV irradiation of TiO2/acetaldehyde suspensions yields the same radical adduct generated when no TiO2 is present—this adduct (assigned to trapped formyl radicals or PBN degradation products) is produced irrespective of the state of oxygenation of solution. Direct sunlight irradiation of deoxygenated TiO2/acetaldehyde suspension results in the production of PBN–acetyl adducts as the primary species. In oxygenated TiO2/acetaldehyde suspension, PBN–acetyl adducts are again produced as the primary species, together with a weakly adducted secondary species—assigned to PBN–acetoxyl adducts. TiO2 band gap transitions are observed to play no part in the production of radical intermediates in sunlight irradiated acetaldehyde/TiO2 suspension. The extent of non-band gap dependent processes is shown to be sensitive to the surface basicity of the metal oxide. Band gap mediated radical production is demonstrated to arise when acetaldehyde photoreduction is coupled to the concomitant photooxidation of ethanol. Ethanol derived PBN–ethoxy adducts are detected as the primary species arising from sunlight irradiation of both oxygenated and deoxygenated TiO2/acetaldehyde/ethanol suspensions.

Effect of calcium channel blocking agents on the reductive metabolism of halothane

The effect of calcium channel blocking agents on the reductive metabolism of halothane in liver microsomes of guinea pigs was investigated. The reaction mixture for the measurement of the end products consisted of microsomal suspension, 5 mM NADPH, calcium channel blocking agents (verapamil, diltiazem, nicardipine and nifedipine) and halothane in 0.1 M phosphate buffer (pH 7.4). The reductive metabolism of halothane was inhibited competitively by verapamil, diltiazem and nicardipine. The binding spectra for the interaction of these three drugs with cytochrome P-450 in microsomes were investigated. Verapamil caused the reverse type I difference spectrum and diltiazem caused the type I difference spectrum. However, the change caused by nicardipine was not observed by the presence of its specific spectra. NADPH-cytochrome P-450 reductase activity in microsomes did not change by the addition of these three drugs. These results suggest that these three calcium channel blocking agents inhibit the production of radical intermediates during the reductive metabolism of halothane.

FLAVIN TRIPLET QUENCHING AND SEMIQUINONE FORMATION BY ALIPHATIC α‐SUBSTITUTED ACETIC ACIDS: INTERMEDIATES IN FLAVIN‐SENSITIZED PHOTODECARBOXYLATION*

Abstract— The quenching of flavin excited states and the production of radical intermediates by aliphatic α‐substituted acetic acids have been investigated using fluorescence and laser photolysis measurements. Stern‐Volmer quenching constants for the flavin triplet are 2–4 orders of magnitude smaller than those found previously for aromatic acids. At the high substrate concentrations required to obtain triplet quenching, singlet quenching, probably via exciplex formation, is also observed. When triplet and radical yields are quantitated, it is found that, for pyruvate, glyoxylate and lactate, quenching occurs virtually exclusively by a one‐electron transfer mechanism. This supports the contention that the flavin‐sensitized photodecarboxylation of these acids proceeds via a radical mechanism.