Semiquinone Research Articles

Mixed-valence, conjugated semiquinones

Mixed-valence, conjugated semiquinones

INTERMEDIARY OXIDATION REACTION BETWEEN THE TWO REDUCTION PHASES DURING THE TRIPHASIC COURSE OF CYTOCHROME b REDUCTION

The reduction of eytochrome b in the succinate-cytoehrome c reduetase by either succinate or duroquinol follows a triphasic course in the pH range 6.0—9.0. The rates of all the three phases of cytochrome b oxldation-reduction as well as the rate of reduction of cytochrome c increase with increasing pH. The course of both the triphasic changes and the multiphasic oxidation-reduction changes of cytochrome b in the presence of added cytochrome c have also been followed by repeated spectral scan at 4℃. In all cases, the reduction and oxidation of cytochrome b are clearly indicated by the appearance and disappearance of the 562 nm peak in the reduced minus oxidized spectra. The accumulation of ubisemiquinone at center i has been suggested to be responsible for the oxidation phase of cytochrome b.

Electron paramagnetic resonance characterization and conformation of daunorubicin semiquinone intermediate implicated in anthracycline metabolism, cardiotoxicity, and anticancer action

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Influence of N-acetylcysteine on the antitumor activity of doxorubicin.

C ONSIDERABLE ATTENTION has been given to doxorubicin-induced cardiomyopathy since its recognition nearly 10 yr ago. Although the mechanism by which doxorubicin (DOX) produces cardiotoxicity is unknown, evidence suggests that it is linked to the effect of free radicals formed during the drug’s metabolism’ (Fig. 1). Handa and Sate* initially showed that DOX metabolism in a microsomal NADPH oxidase system yielded superoxide anion (0;;). Goodman and Hochstein3 demonstrated that, in the reduction-oxidation cycle of DOX 1 molecule in the quinone form could cycle to a semiquinone then back to the quinone form many times to generate molecules of superoxide anion and initiate lipid peroxidation. When Bachur et aL4 demonstrated that heart microsomes from rats were capable of supporting the generation of free radicals from DOX, it was suggested that a free radical oxidative mechanism might mediate the cardiotoxicity of this drug. This concept was supported by data from Myers et al.’ and Olson et al.6 demonstrating that the antioxidant vitamin E and the free radical scavenger cysteamine attenuated the acute cardiotoxicity of DOX in mice. The glutathione peroxidase pathway (Fig. 2), which detoxifies potentially damaging peroxides by reducing them to alcohols, also was shown to be an important modulator of DOX-induced cardiotoxicity.‘.’ Depletion of endogenous glutathione by diethyl maleate’.’ and inhibition of glutathione peroxidase by reduction of endogenous selenium stores (selenium is a required cofactor of glutathione peroxidase activity)‘dramatically potentiated DOX-induced cardiotoxicity in laboratory animals. Furthermore, pretreatment of rabbits with diethyl maleate to lower endogenous cardiac glutathione levels to less than 30% of basal values significantly potentiated the negative inotropic activity of DOX in isolated papillary muscles obtained from pretreated rabbits.’ Additionally, studies with Nacetylcysteine (NAC) have shown this agent to provide significant protection against DOXinduced cardiotoxicity.“,”

Differential kinetic determination of mixtures of aniline and its derivatives using N,N-dimethyl-p-phenylenediamine.

The oxidative coupling reaction between the quinonediimine (QDI) of N, N-dimethyl-p-phenylenediamine (DMPD) and aromatic amines was utilized for the simultaneous determination of binary mixtures of aniline and its derivatives by the differential reaction rate method. A mixture of oxidant and DMPD was used instead of QDI because QDI was unstable. The effects of pH and the oxidant (K3Fe (CN)6, K2Cr2O7 and their mixture) on the stability of the first oxidation product of DMPD, semiquinone (SQ), and on the equilibrium among DMPD, SQ and QDI, were investigated. The second-order rate constants of two amines reacting with QDI and the overall pseudo first-order rate constant of a mixture were determined from the slope of the straight line (the concentration of SQ vs. time) and by simplified complementary tristimulus colorimetry. Mixtures of amines down to 1.0×10-4M were determined. Most relative errors were in the range of 0 to 14%. Among the compounds examined for interference, phenols and carbonyl compounds showed serious effects.

Photooxidation of chlorins by quinones studied by nuclear magnetic resonance techniques

The reactions of photo-excited chlorophylls and pheophytins with quinones have been investigated by nuclear magnetic resonance techniques. In slightly alkaline solutions the quinone signals showed line broadening which is explained by degenerate electron transfer between semiquinone radical ions and their benzoquinone parents. In neutral solutions, chemically induced dynamic nuclear polarization was observed which is ascribed to the pair, chlorophyll cation-semiquinone anion. A kinetic analysis of the dependence of these effects upon the quinone concentration suggests that only the reactions of triplet-chlorophyll with the quinones give rise to chemically induced dynamic nuclear polarization effects.

An ESR and ENDOR study of spin relaxation of semiquinones in liquid solution

A quantitative test of the ENDOR theory for free radicals in solution has been developed experimentally using the semiquinone (SQ) radical anions of parabenzo- (PBSQ), duro- (DSQ), and 2,5-dimethyl-para-benzo- (2,5-DPMBSQ) dissolved in ethyl alcohol (EtOH) and dimethoxyethane (DME) solvents. It is shown that, in general, an ENDOR signal arising from a molecule containing four or less equivalent nuclei, such as PBSQ, can be analyzed rigorously whereas a molecule containing more than four equivalent nuclei, such as DSQ, which, in principle, could be analyzed rigorously, practically is best analyzed using approximate forms of the ENDOR theory. It is shown that 2,5-DMPBSQ may be analyzed using a combination of both the rigorous and approximate forms of the ENDOR theory. The analysis involves calculation of the ENDOR relaxation parameters, T2n, Ωn, and Ωe,n, from the experimental ENDOR percent enhancement and linewidth studies. A comparison was made by performing the ESR linewidth and saturation studies to obtain values of We, the electron spin–lattice relaxation probability, and Wn, the nuclear spin-relaxation probability and then using this information to predict the observed ENDOR relaxation parameters in terms of the theory. The over-all behavior of the experimental results was found to be fully consistent with the general trends predicted by the theory and expected from the quantitative measurements obtained from the ESR studies. This work describes in detail the instrumentation and experimental methods necessary to measure relaxation parameters of organic free radicals in solution. A comprehensive section describing the effects of modulation amplitude, microwave power, coherence broadening or splitting, and pulse rate is given along with methods for analyzing ENDOR line shapes in their presence. The results and analyses of all ESR and ENDOR experiments are described in detail. Analysis of the rotational correlation time τR, obtained from the ESR studies, shows the radical anions in DME solution are most likely solvated and affected by the counterion and/or supporting electrolyte while PBSQ in EtOH is most likely dissociated. A comparison of the experimental and theoretical magnitudes of We leads to the possibility that for small molecules in liquids a Brownian model of reorientation by infinitesimal jumps need not be satisfactory and that jumps of large angle would be needed to better fit the experimental data. The effect of Heisenberg exchange on ENDOR signals is analyzed and discussed in detail, leading to the conclusion that the intermolecular electron–electron dipolar interaction as well as Heisenberg exchange make contributions to the concentration dependent portion of the linewidth. However, the latter contributes much more to the ESR linewidths as compared to the ENDOR widths for PBSQ in EtOH. The above analysis is modified to include charge effects. Finally it is shown that for methyl group ENDOR cross relaxation from modulation of the isotropic hyperfine splitting via methyl group rotation is not the dominant nuclear relaxation mechanism and all methyl group ENDOR analyses are consistent with a Wn derived from the pseudosecular terms of the anisotropic electron–nuclear dipolar interaction.

Observation of the Semiquinone of Benzoquinone

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Additions and Corrections - Some Properties of Phenanthrene Semiquinone

Additions and Corrections - Some Properties of Phenanthrene Semiquinone

The Paramagnetism of the Semiquinone of Phenanthrenequinone-3-sulfonate

The Paramagnetism of the Semiquinone of Phenanthrenequinone-3-sulfonate

Supplement to a Recent Paper on the Paramagnetism of Semiquinones

Supplement to a Recent Paper on the Paramagnetism of Semiquinones