- EPR studies of the formation and transformation of isomeric radicals [C3H5O].. Rearrangement of the allyloxyl radical in non-aqueous solution involving a formal 1,2-hydrogen-atom shift promoted by alcohols
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At 220 K in cyclopropane solvent, hydrogen-atom abstraction from allyl alcohol by Bu'O., EtO., PhMe2CO., (Me3Si)2N. or triplet-state acetone gives the 1-hydroxyallyl radical 3 as a ca. 3:1 mixture of the syn- and anti-isomers. In contrast, the allyloxyl radical does not react with allyl alcohol to bring about abstraction of hydrogen, but instead undergoes a more rapid alcohol-promoted rearrangement to give 3 as a ca. 1:1 mixture of the syn- and anti-forms. 2-Methylallyl alcohol, ethanol and propan-2-ol also induce this formal 1,2-H-atom shift in the allyloxyl radical. In the presence of ethan[2H]ol, both 3 and (3-OD) are formed and as [EtOD] is increased from 0.3 to 3.6 mol dm-3 [3-OD]/[3] first passes through a maximum value of ca. l and then decreases to 0.38. It is proposed that there is more than one mechanism for the alcohol-induced rearrangement of the allyloxyl radical, one that involves assisted migration of hydrogen from the α-carbon atom to the oxygen atom and another that results in incorporation of deuterium from the EtOD. The importance of the latter mechanism decreases at high alcohol concentrations and this behaviour is thought to be related to the extent of association of the alcohol by hydrogen-bonding. The allyloxyl radical was generated by UV photolysis of allyl tert-butyl peroxide and by ring opening of the oxiranylmethyl radical, derived from epibromohydrin or epichlorohydrin by halogen-atom abstraction. Ab initio molecular orbital calculations predict that an unassisted 1,2-H-atom shift in the allyloxyl radical will involve a very large activation energy. The alcohol is believed to serve a dual function in promoting the rearrangement: first, to increase the acidity of the α-CH2 group by hydrogen-bonding to the oxygen atom of the allyloxyl radical and, secondly, to provide a basic oxygen atom to facilitate the transfer/removal of a protic α-hydrogen atom.
- Elford, Patrick E.,Roberts, Brian P.
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- On the mechanism of reaction of radicals with tirapazamine
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Ketyl radicals produced by photolysis of ketones or di-tert-butyl peroxide (DTBP) in alcohol solvents react rapidly with tirapazamine (TPZ). The acetone ketyl radical (ACOH) reacts with TPZ with an absolute second-order rate constant of (9.7 ± 0.4) × 108 M-1 s-1. The reaction kinetics can be followed by monitoring the bleaching of TPZ absorption at 475 nm or the formation of a reaction product which absorbs at 320 and 410 nm. The ACOD radical reacts with TPZ in 2-propanol-OD with an absolute rate constant of (6.7 ± 0.5) × 108 M-1 s -1 corresponding to a kinetic isotope effect (KIE) of 1.4. Deuteration of the radical on carbon (ACOH-d6) retards the reaction of the radical with TPZ even further (absolute rate constant = (4.8 ± 0.04) × 108 M-1 s-1). This result corresponds to a KIE of 2.0. Radicals derived from dioxane and diisopropyl ether by flash photolysis of DTBP in ethereal solvent react with TPZ more slowly than do ketyl radicals. It is concluded that ketyl radicals react, in part, with TPZ in organic solvents by transfer of a hydrogen atom from the OH and CH 3 groups of the ketyl radical to the oxygen atom at the N4 position of TPZ to form acetone or acetone enol and a radical derivative of TPZ (TPZH). The latter species absorbs at 320 and 405 nm, has a lifetime of hundreds of microseconds in alcohol solvents, and decays by disproportionation to form TPZ and a reduced heterocycle. The reduced heterocycle eventually forms a desoxytirapazamine by a polar mechanism. The results are supported by density functional theory calculations. It is proposed that dioxanyl radical will also react, in part, with TPZ by transfer of a hydrogen atom from the carbon adjacent to the radical center to the oxygen atom at the N4 position of TPZ. This produces the enol ether and the previously mentioned TPZH radical. It is further posited that ether radicals react a bit more slowly than ketyl radicals because they lack the second mode of hydrogen transfer (from the OH group) that is present in the ACOH radical. Our data are permissive of the possibility that ether radicals add to TPZ at a rate that is competitive with β-hydrogen atom transfer.
- Shi, Xiaofeng,Mandel, Sarah M.,Platz, Matthew S.
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p. 4542 - 4550
(2007/10/03)
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- Kinetics of the gas-phase reactions of NO3 radicals with a series of alcohols, glycol ethers, ethers and chloroalkenes
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Using a relative rate method, rate constants have been measured for the gas-phase reactions of the NO3 radical with methacrolein, a series of ethers, glycol ethers, alcohols and chloroalkenes at 298 ± 2 K and atmospheric pressure of air. The rate constants determined (in units of 10-16 cm3 molecule-1 s-1) were: methacrolein, 33 ± 10; diethyl ether, 31 ± 10; di-n-propyl ether, 49 ± 16; diisopropyl ether, 40 ± 13; ethyl tert-butyl ether, 45 ± 14; 1-methoxypropan-2-ol, ≤15 ± 5; 2-butoxyethanol, ≤31 ± 11; propan-1-ol, ≤21 ± 8; propan-2-ol, ≤17 ± 6; butan-1-ol, ≤27 ± 10; butan-2-ol, ≤25 ± 8; heptan-4-ol, ≤60 ± 20; cis-1,2-dichloroethene, 1.3 ± 1.3; 1,1-dichloroethene, 18-6+9; trichloroethene, 3.6-1.5+2.0; tetrachloroethene, -2.0+3.0. Carbonyl products of the alcohol reactions arising after H-atom abstraction at the carbon atom to which the -OH group is attached were observed, and rate constants for this reaction pathway obtained. Significant discrepancies with the literature concern propan-2-ol, ethyl tert-butyl ether and 3-chloropropene, with our relative rate constants for these compounds being factors of ca. 2, ca. 2, and ca. 8 lower, respectively, than previously reported absolute rate constant determinations.
- Chew, Andrew A.,Atkinson, Roger,Aschmann, Sara M.
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p. 1083 - 1089
(2007/10/03)
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- Indolequinone antitumor agents: Reductive activation and elimination from (5-methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl derivatives and hypoxia- selective cytotoxicity in vitro
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A series of indolequinones bearing a variety of leaving groups at the (indol-3-yl)methyl position was synthesized by functionalization of the corresponding 3-(hydroxymethyl)indolequinone, and the resulting compounds were evaluated in vitro as bioreductively activated cytotoxins. The elimination of a range of functional groups-carboxylate, phenol, and thiol- was demonstrated upon reductive activation under both chemical and quantitative radiolytic conditions. Only those compounds which eliminated such groups under both sets of conditions exhibited significant hypoxia selectivity, with anoxic:oxic toxicity ratios in the range 10-200. With the exception of the 3-hydroxymethyl derivative, radiolytic generation of semiquinone radicals and HPLC analysis indicated that efficient elimination of the leaving group occurred following one-electron reduction of the parent compound. The active species in leaving group elimination was predominantly the hydroquinone rather than the semiquinone radical. The resulting iminium derivative acted as an alkylating agent and was efficiently trapped by added thiol following chemical reduction and by either water or 2-propanol following radiolytic reduction. A chain reaction in the radical-initiated reduction of these indolequinones (not seen in a simpler benzoquinone) in the presence of a hydrogen donor (2-propanol) was observed. Compounds that were unsubstituted at C-2 were found to be up to 300 times more potent as cytotoxins than their 2-alkyl-substituted analogues in V79-379A cells, but with lower hypoxic cytotoxicity ratios.
- Naylor, Matthew A.,Swann, Elizabeth,Everett, Steven A.,Jaffar, Mohammed,Nolan, John,Robertson, Naomi,Lockyer, Stacey D.,Patel, Kantilal B.,Dennis, Madeleine F.,Stratford, Michael R. L.,Wardman, Peter,Adams, Gerald E.,Moody, Christopher J.,Stratford, Ian J.
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p. 2720 - 2731
(2007/10/03)
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- Time-Resolved Fluorescence Monitoring of Aromatic Radicals in Photoinitiated Processes
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Photolytic initiation of free radical reactions is important to many areas of technology; time-resolved monitoring of submicromolar concentrations of radicals produced during the course of these reactions is needed to provide information about the rate of initiation and its competition with radical recombination. In this work, time-resolved laser-induced fluorescence is evaluated for monitoring of diphenylketyl radicals produced by photoreduction of the triplet state of benzophenone. Fluorescence from the doublet-doublet transition of the radical is excited with a continuous wave laser and provides a sensitive method to detect these intermediates at nanomolar concentrations and to study their kinetics in solution on time scales from a few microseconds to hundreds of milliseconds. The ketyl radical fluorescence measurements of radical initiation reactions allowed the H atom abstraction rate constant by triplet benzophenone from both 2-propanol and benzhydrol to be determined, where kH = (2.1 ± 0.1) × 106 M-1 s-1 for 2-propanol and kH = (4.4 ± 0.1) × 106 M-1 s-1 for benzhydrol. The diphenylketyl radical recombination rate constant was also determined by time-resolved fluorescence monitoring of the decay of the radical population and found to be kr = (1.9 ± 0.2) × 108 M-1 s-1. Formation kinetics could be measured on a microsecond time scale from radical populations as low as 45 nM; decay kinetics could be followed on a millisecond time scale from 20 nM radical concentrations.
- Shield, Stephanie R.,Harris, Joel M.
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p. 2576 - 2583
(2007/10/03)
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- The reactivity of ketyl and alkyl radicals in reactions with carbonyl compounds
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A parabolic model of bimolecular radical reactions was used for analysis of the hydrogen transfer reactions of ketyl radicals: >C+OH + R1COR2 → >C=O + R1R2C+OH. The parameters describing the reactivity of the reagents were calculated from the experimental data. The parameters that characterize the reactions of ketyl and alkyl radicals as hydrogen donors with olefins and with carbonyl compounds were obtained: >C+OH + R1CH=CH2 → >C=O + R1C+ HCH3; >R1CH=CH2 + R2C+HCH2R3 → R2C+HCH3 + R2CH=CHR3. These parameters were used to calculate the activation energies of these transformations. The kinetic parameters of reactions of hydrogen abstraction by free radicals and molecules (aldehydes, ketones, and quinones) from the C-H and O-H bonds were compared.
- Denisov
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p. 2110 - 2116
(2007/10/03)
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- Determination of Absolute Rate Constants for the Reversible Hydrogen-atom Transfer between Thiyl Radicals and Alcohols or Ethers
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Absolute rate constants have been determined for the reversible hydrogen-transfer process R. + RSH ->/. by pulse radiolysis, mainly through direct observation of the RS. radical formation kinetics in water-RH (1:1, v/v) mixtures.The thiols investigated were penicillamine and glutathione; the RH hydrogen donors were methanol, ethanol, propan-1-ol, propan-2-ol, ethylene glycol, tetrahydrofuran and 1,4-dioxane with the abstracted hydrogen being located α to the hydroxy or alkoxy function.Rate constants for the forward reaction of the above equilibrium (in radiation biology referred to as 'repair' reaction) were typically of the order of 1E7-1E8 dm3 mol-1 s-1 while hydrogen abstraction from RH by thiyl radicals (reverse process) occurred with rate constants of the order of 1E3-1E4 dm3 mol-1 s-1.This yields equilibrium constants of the order of 1E4.Based on these data, standard reduction potentials could be evaluated for the R'R''C.OH/H(1+)//R'R''CHOH, R'R''CO/H(1+)//R'R''C.(OH) and R'R''CO//R'R''C.O(1-) couples from methanol, ethanol and propan-2-ol.Effective hydrogen-atom abstraction by RS. required activation by neighbouring groups of the C-H bond to be cleaved in RH.No such process was observed for the RS. reaction with -CH3 groups, e.g. in 2-methylpropan-2-ol.Several halogenated hydrocarbons, including some anaesthetics (e.g. halothane) and Fe(CN)6(3-) have been tested with respect to their ability to disturb the (CH3)2C.OH + RSH ->/. equilibrium through an irreversible electron-transfer reaction with the reducing α-hydroxyl radical, thereby drawing the equilibrium to the left-hand side.The respective efficiencies are found to be related to the electronegativities of the electron acceptors.The results are briefly discussed in terms of their biological relevance.
- Schoeneich, Christian,Asmus, Klaus-Dieter,Bonifacic, Marija
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p. 1923 - 1930
(2007/10/02)
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- Unique Pressure Effects on the Absolute Kinetics of Triplet Benzophenone Photoreduction in Supercritical CO2
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Laser flash photolysis studies of the hydrogen atom abstraction reaction of triplet benzophenone from 2-propanol and 1,4-cyclohexadiene in supercritical CO2 reveal unusual pressure effects on absolute rate constants.Monitoring reactivity close to the critical temperature (Tc) revealed that bimolecular rate constants increase sharply with a decrease in pressure, approaching the critical point.Kinetic investigations along an isotherm further removed from Tc and predictive calculations on the pressure effect expected in supercritical CO2 indicate that enhanced reactivity is due to local substrate clustering.
- Roberts, Christopher B.,Chateauneuf, John E.,Brennecke, Joan F.
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p. 8455 - 8463
(2007/10/02)
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- Homolytic decomposition of tertiary organochromium(III) complexes and evidence for their decomposition via reactions with aliphatic free radicals. A pulse radiolysis study
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The rates of homolytic decomposition of Cr-C(CH3)2OH2+-, Cr-C(CH3)2CO2H2+, and Cr-C(CH3)2CN2+ are 0.15 s-1, 4 s-1, and 104 -6 s-1, respectively. The reaction of some aliphatic free radicals,·R with CrIII-R complexes is very fast, K3 ≥ 108 M-1 S-1. The rate of reaction of Cr2+(aq) with H2O2 is k16 = (3.7 ±0.7) × 104 M-1 s-1 in good accord with the literature value. These results are discussed in detail.
- Mulac, William A.,Cohen, Haim,Meyerstein, Dan
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p. 4016 - 4020
(2008/10/08)
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