2395-99-5Relevant academic research and scientific papers
Investigating the mechanisms of aromatic amine-induced protein free radical formation by quantitative structure-activity relationships: Implications for drug-induced agranulocytosis
Siraki, Arno G.,Jiang, Jinjie,Mason, Ronald P.
experimental part, p. 880 - 887 (2011/03/17)
Aromatic amine drugs have been associated with agranulocytosis (neutrophil depletion) for which the mechanism is unknown. We have previously shown that the metabolism of two aromatic amine drugs by human myeloperoxidase (MPO) results in phenyl radical metabolite formation and also in protein free radical formation on MPO. Because the concentration of drug required to produce a maximum signal for MPO protein free radical (MPO?) detection was different for each drug, this prompted us to consider that other aromatic amines may also show varying degrees of ability to induce MPO? formation. Immunoassay experiments using the immuno-spin-trapping technique were performed, which evaluated the potency of different aromatic amines containing the aniline substructure to generate the MPO?. Each reaction contained equal amounts of H2O2, 5,5-dimethyl-1-pyrroline- N-oxide, MPO, and variable concentrations of aniline derivatives. Several physicochemical parameters for aniline derivatives were used to derive quantitative structure-activity relationship equations, which showed that the Hammett constant (-) best correlated with the MPO? formation for all aniline derivatives. More statistically robust equations were derived if the anilines were separated into mono- and disubstituted groups. However, some aniline derivatives did not induce MPO? formation. Using electron spin resonance spectroscopy, we evaluated the ability of all aniline derivatives tested to produce phenyl radical metabolites, as previously shown by spin trapping for the aromatic amine drugs. Interestingly, we found that only those aniline derivatives that produced a phenyl radical also formed MPO ?. We propose that the phenyl radical is the reactive free radical metabolite responsible for generating the MPO?+.
Application of a new kinetic method in the investigation of cleavage reactions of haloaromatic radical anions
Enemaerke, Rasmus J.,Christensen, Torben B.,Jensen, Henrik,Daasbjerg, Kim
, p. 1620 - 1630 (2007/10/03)
A simple kinetic method based on competition kinetics is presented for the measurement of cleavage rate constants of radical anions over the range of 107 - 5 × 109 s-1 in aprotic solvents. The standard potential for the formation of the radical anions may be extracted from the kinetic analysis as well. The method employs electrochemical steady-state or optical detection techniques and is an extension of the redox catalysis approach described previously in the literature. The applicability of the method is illustrated through a systematic study of the cleavage reactions for a number of short-lived haloaromatic radical anions. Interestingly, the radical anion of iodobenzene is found to be an intermediate in the homogeneous reduction of iodobenzene, even though recent investigations have shown that the corresponding heterogeneous reduction at an electrode surface proceeds by a concerted electron transfer-bond cleavage process. The nature of the cleavage reactions is discussed in terms of the activation driving force plot of the cleavage rate constants versus the relevant Gibbs energies. While the exergonic cleavage reactions follow a simple decay mechanism taking place at the halogen site, the endergonic processes are best described as intra-molecular electron transfers from the substituent to the carbon-halogen bond. Nevertheless, the overall intrinsic barrier is found to be relatively small (27-39 kJ mol-1) and it is suggested that the endergonic reactions may proceed by a stepwise mechanism, in which a σ* radical anion is formed as an intermediate prior to the formation of the dissociated products, the aryl radical and the halide. The above conclusions were supported by semi-empirical PM3 calculations of structures and charge distributions in the radical anions.
Thermal properties of 1,1′-bis(p-substituted-benzoyloxy-substituted-phenyl)cyclohexanes
Rajkotia,Parsania
, p. 24 - 27 (2007/10/03)
DSC thermograms of 1,1′-bis(p-substituted-benzoyloxy-substituted-phenyl)cyclohexanes 3, 8, 14 and 15 showed two endotherms whereas 2, 4-7, 9, 11-13, 16 and 17 showed more than two endotherms indicating formation of new compounds as a result of decomposition of original compound. TG thermograms of 1, 2, 4, 5, 8, 11-13 and 15 involved a single step decomposition whereas 3, 6, 7, 9, 10, 14, 16 and 17 involved two step degradation and involved first order kinetics.
Kinetic and mechanistic studies of the nonchain radical nucleophilic substitution reactions
Zhang,Yang,Jia,Liu
, p. 7350 - 7354 (2007/10/02)
The kinetics of the radical nucleophilic substitution reaction of p- nitrochlorobenzene with the sodium salt of the ethyl α-cyanoacetate carbanion in dimethyl sulfoxide (DMSO) solution at 335.9, 340.1, 343.9, 347.7, and 351.4 K were determined by observing the increase of the UV- visible absorbance of the product, the ethyl α-cyano-α-(p- nitrophenyl)acetate carbanion. The activation energies and entropies for the single electron transfer (k1) and for the p-nitrochlorobenzene radical anion dissociation (k2) were obtained. These results strongly support the previous conclusion that the thermal nucleophilic substitution reactions of o- and p- nitrohalobenzenes with the sodium salt of ethyl α-cyanoacetate carbanion in DMSO solution proceed exclusively via a nonchain radical mechanism (Scheme II).
Free-Radical Reductions of Arenediazonium Ions in Aqueous Solution. V. Pulse-Radiolytic Determination of Rate Constants for Some para-Substituted Benzenediazonium Ions
Packer, John E.,Moenig, Joerg,Dobson, Brian C.
, p. 1433 - 1441 (2007/10/02)
Some rate constants for the reduction of para-substituted benzenediazonium ions by the radicals eaq-, .CH2OH, (CH3)2.COH and some semiquinone radical anions have been measured.The substituent group has no effect on the rates with eaq-, but as the reduction potential of the reducing radical becomes more positive, the substituent effect increases, electron-withdrawing groups enhancing the rates.No free halide is formed on reduction of p-BrC6H4N2+ or p-IC6H4N2+ by eaq- or .CH2OH.
Free-Radical Reductions of Arenediazonium Ions in Aqueous Solution. IV. Kinetics of Reactions of para-Substituted Diazonium Ions with Benzyl Alcohol, Isopropyl Alcohol And Methanol
Packer, John E.,Heigway, Christopher J.,Miller, Helen M.,Dobson, Brian C.
, p. 965 - 977 (2007/10/02)
Electron-withdrawing substituents are shown to increase the chain length of free-radical hydrodediazoniation reactions, but the actual reaction step causing the substituent effect depends on the relative rates of propagation and termination reactions.With benzyl alcohol as reducing agent the rate of the slow propagation step is increased, while with isopropyl alcohol the rate of the termination step is decreased.Rate constants for some reactions of radicals with diazonium ions are reported, and the nature of some of these reactions and their implication foran understanding of the homolysis of aromatic diazo compounds are discussed.
