- Formation of methyl radicals derived from cumene hydroperoxide in reconstructed human epidermis: an EPR spin trapping confirmation by using 13C-substitution
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Dermal exposure to cumene hydroperoxide (CumOOH) during manufacturing processes is a toxicological issue for the industry. Its genotoxicity, mutagenic action, ability to promote skin tumour, capacity to induce epidermal hyperplasia, and aptitude to induce allergic and irritant skin contact dermatitis are well known. These toxic effects appear to be mediated through the activation to free radical species such as hydroxyl, alkoxyl, and alkyl radicals characterised basically by electron paramagnetic resonance (EPR) and spin-trapping (ST) techniques. To be a skin sensitiser CumOOH needs to covalently bind to skin proteins in the epidermis to form the antigenic entity triggering the immunotoxic reaction. Cleavage of the O–O bond allows formation of unstable CumO?/CumOO? radicals rearranging to longer half-life specific carbon-centred radicals R? proposed to be at the origin of the antigen formation. Nevertheless, it is not still clear which R? is precisely formed in the epidermis and thus involved in the sensitisation process. The aim of this work was to elucidate in conditions closer to real-life sensitisation which specific R? are formed in a 3D reconstructed human epidermis (RHE) model by using 13C-substituted CumOOH at carbon positions precursors of potentially reactive radicals and EPR-ST. We demonstrated that most probably methyl radicals derived from β-scission of CumO? radicals occur in RHE through a one-electron reductive pathway suggesting that these could be involved in the antigen formation inducing skin sensitisation. We also describe a coupling between nitroxide radicals and β position 13C atoms that could be of an added value to the very few examples existing for the coupling of radicals with 13C atoms.
- Sahli, Fatma,Godard, Amélie,Vileno, Bertrand,Lepoittevin, Jean-Pierre,Giménez-Arnau, Elena
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p. 737 - 747
(2019/06/25)
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- A highly active and air-stable ruthenium complex for the ambient temperature anti-markovnikov reductive hydration of terminal alkynes
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The conversion of terminal alkynes to functionalized products by the direct addition of heteroatom-based nucleophiles is an important aim in catalysis. We report the design, synthesis, and mechanistic studies of the half-sandwich ruthenium complex 12, which is a highly active catalyst for the anti-Markovnikov reductive hydration of alkynes. The key design element of 12 involves a tridentate nitrogen-based ligand that contains a hemilabile 3-(dimethylamino) propyl substituent. Under neutral conditions, the dimethylamino substituent coordinates to the ruthenium center to generate an air-stable, 18-electron, κ3-complex. Mechanistic studies show that the dimethylamino substituent is partially dissociated from the ruthenium center (by protonation) in the reaction media, thereby generating a vacant coordination site for catalysis. These studies also show that this substituent increases hydrogenation activity by promoting activation of the reductant. At least three catalytic cycles, involving the decarboxylation of formic acid, hydration of the alkyne, and hydrogenation of the intermediate aldehyde, operate concurrently in reactions mediated by 12. A wide array of terminal alkynes are efficiently processed to linear alcohols using as little as 2 mol % of 12 at ambient temperature, and the complex 12 is stable for at least two weeks under air. The studies outlined herein establish 12 as the most active and practical catalyst for anti-Markovnikov reductive hydration discovered to date, define the structural parameters of 12 underlying its activity and stability, and delineate design strategies for synthesis of other multifunctional catalysts.
- Zeng, Mingshuo,Li, Le,Herzon, Seth B.
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supporting information
p. 7058 - 7067
(2014/06/09)
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- Iron-catalyzed three-component reaction: Multiple C-C bond cleavages and reorganizations
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An unexpected three-component iron-catalyzed reaction, comprising C-C bond cleavages in two components together with three times the cyclopropane formation and ring opening, is developed. The current reaction provides an unprecedented and efficient approa
- Wang, Peng,Liao, Saihu,Zhu, Jian-Bo,Tang, Yong
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supporting information
p. 3606 - 3609
(2013/08/23)
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- Propynal equivalents and diazopropyne: Synthesis of all mono-13C isotopomers
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Mechanistic and spectroscopic investigations of reactive C 3H2 hydrocarbons necessitated the preparation of diazopropyne isotopomers bearing mono-13C substitution at each of the three unique positions. The diazo compounds and their tosylhydrazone precursors were prepared from the mono-13C isotopomers of propynal (in the form of either the aldehyde or the diethyl acetal). The introduction of 13C-labeling at either alkyne position in propynal utilized the Corey - Fuchs procedure for chain homologation.
- Seburg, Randal A.,Hodges, Jonathan A.,McMahon, Robert J.
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experimental part
p. 1626 - 1643
(2009/10/17)
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- Rearrangement of indene skeletons under mild conditions
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(Chemical Equation Presented) Isomerization between two isomers of 1,2-disubstituted 3-aminoindenes occurs via the rearrangement of indene frameworks. In contrast to previous rearrangements of indene derivatives, which occur under high-temperature conditi
- Kuninobu, Yoichiro,Ueda, Hirokazu,Kawata, Atsushi,Takai, Kazuhiko
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p. 6749 - 6752
(2008/02/11)
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- 13C and 1H nuclear magnetic resonance of methyl-substituted acetophenones and methyl benzoates: Steric hindrance and inhibited conjugation
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The 1H and 13C NMR spectra of 14 methyl-substituted acetophenones and 14 methyl-substituted methyl benzoates were assigned and interpreted with respect to the conformation of the Car - C(O) bond. The substituent effects are proportional in the two series and can be divided into polar and steric: each has different effects on the 13C SCS of the individual atoms. In the case of C atoms C(O), C(1) and CH3(CO), the steric effects were quantitatively separated by comparing SCS in the ortho and para positions. The steric effects are proportional for the individual C atoms and also to steric effects estimated from other physical quantities. However, they do not depend simply on the angle of torsion φ of the functional group as anticipated hitherto. A better description distinguishes two classes of compounds: sterically not hindered or slightly hindered planar molecules and strongly sterically hindered, markedly non-planar. In order to confirm this reasoning without empirical correlations, the J(C,C) coupling constants were measured for three acetophenone derivatives labeled with 13C in the acetyl methyl group. The constants confirm unambiguously the conformation of 2-methylacetophenone; their zero values are in accord with the conformation of 2,6-dimethylacetophenone. The zero values in the unsubstituted acetophenone are at variance with previous erroneous report but all J(C,C) values are in accord with calculations at the B3LYP/6-311++G(2d,2p)// B3LYP/6-311+G(d,p) level. Copyright
- Budesinsky, Milos,Kulhanek, Jiri,Boehm, Stanislav,Cigler, Petr,Exner, Otto
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p. 844 - 851
(2007/10/03)
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- The carbonyl group as a reluctant transmitter of hyperconjugative or ?-? spin-spin coupling interactions in derivatives of benzaldehyde, acetophenone, and benzophenone
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Unlike their counterparts in anisole or toluene derivatives, the six-bond spin-spin coupling constants bentween para ring protons or (19)F nuclei and protons or (13)C nuclei in the sidechain of derivatives of benzaldehyde, acetophenone, and benzophenone c
- Schaeffer, Ted,Peeling, James,Penner, Glenn H.,Lemire, Alberta,Laatikainen, Reino
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p. 1859 - 1863
(2007/10/02)
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- Thermal Stereomutations of (2R,3R)-Phenylcyclopropane-1,2,3-2H3 and (1R,2S,3R)-Phenylcyclopropane-2-13C-1,2,3-2H3: Quantification of All Four Stereochemical Modes for Interconversions among the 1-Phenyl-1,2,3-trideuterocyclopropanes
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Optically pure (2R,3R)-phenylcyclopropane-1,2,3-2H3 and (1R,2S,3R)-phenylcyclopropane-2-13C-1,2,3-2H3 have been prepared and the thermal stereomutations they exhibit have been followed kinetically at 309.3 deg C to provide the first complete quantificatio
- Baldwin, John E.,Barden, Timothy C.
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p. 5312 - 5319
(2007/10/02)
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