Disulfide radical anions, oxidation

A third possibility, in which a highly favorable outer-sphere oxidation of disulfide radical anions to neutral disulfides, Eq. (38), becomes ratedetermining, will yield... 

Disulfide radical anions might play an important role in oxidative stress. In cellular media, they can be formed by oxidation of protein thiol functions (by OH radicals, for instance. Chapter 1), followed by dimerization ... 

These disulfide radical anions are believed to be strong reductants. Thus they might counterbalance the action of oxidizing free radicals. 

Of even greater importance appear to be the consequences of equilibrium 26 with respect to the redox properties. As has been stated already, thiyl radicals are oxidants. Disulfide radical anions, on the other hand, are reductants (E° = -1.5 V).51 The transfer of their antibonding electron to oxygen is of particular interest, especially in biological systems.63,65... 

Complexation of thiyl radicals with thiolate anions to form disulfide radical anions RSSR" is a well established process in fluid solution. The formation of RSSR" from thiyl radicals and thiols has also been observed in glasses where thiyl radicals were generated through either direct photolysis [9, 93, 94] of the thiol or its oxidation by other species (0 and CI2") formed on 7-irradiation in aqueous glasses [20]. This happens even when basicity of the medium does not allow thiolate anions to exist in appreciable concentrations [95]. A suspected intermediate in this case is the RSS(H)R adduct which deproto-nates under the same conditions, since it is more acidic than the parent thiol [10, 11] ... 

The observed rate laws for the oxidation of mercaptoethanol by methylene blue under different reaction conditions are consistent with the steady-state rate laws derived from the proposed mechanism. If step 2 of the reaction sequence, namely formation of the disulfide radical anion from a thiyl radical and a sulfide ion, is the rate limiting step of the chain sequence, and therefore only termination by 6 (coupling of thiyl radicals) occurs, the derived rate law for the reaction is Eq. 11. This rate law, which takes.into account the distribution of the thiol and sulfide as determined by the of the thiol and the acidity of the medium, predicts that the observed rate law would be half order in MB and three halves order in mercaptoethanol. This is the rate law expected, however, only if the concentration of MB " is sufficiently high so that the second term in the denominator is neglible. At pH s below the pH maximum, and at a sufficiently... 

If the dithioerythritol oxidations do indeed follow the same mechanistic path as the mercaptoethanol oxidations with respect to relative reagent concentrations, at pH s below that observed for the maximum rate and at the high concentrations of MB , only the unimolecular disulfide radical anion formation (reaction 15) would be rate limiting. The derived rate law based on only... 

The effects of pH, ionic strength, reagent concentration ratios and deuterium substitution of the sulfur-bonded hydrogens on both the rates and rate laws for the methylene blue oxidations of mercaptoethanol and dithioerythritol have been determined. A free radical chain mechanism consistent with the observed kinetic behavior of the oxidation reactions is proposed. A key feature of the proposed mechanism is the formation of the sulfur-sulfur linkage of the disulfide in the reversible formation of a disulfide radical anion (RSSR) as a chain propagating step in the chain sequence. 

Thiols are susceptible to oxidation by peroxides, molecular oxygen, and other oxidizing processes (e.g., radical-catalyzed oxidation) (Fig. 67). Because thiols easily complex with transition metals, it is believed that most thiol autoxidation reactions are metal-catalyzed (108). Autoxidation of thiols is enhanced by deprotonation of the thiol to the thiolate anion. Thiol oxidation commonly leads to disulfides, although further autoxidation to the sulfinic and, ultimately, sulfonic acid can be accomplished under basic conditions. Disulfides can be reduced back to the thiol (e.g., upon addition of a reducing agent such as dithiothreitol). Thiols are nucleophilic and will readily react with available electrophilic sites. For a more thorough discussion, see Hovorka and Schoneich (108) and Luo et al. (200). 

Another example of a coupling reaction initiated by reaction of the radical anion with an electrophile is the reductive coupling of substituted 4/f-pyran-4-thiones (34) in the presence of alkyl halides (Scheme 8) [110,111]. The neutral radical formed by alkylation at sulfur is apparently not reduced at the potential of the electrolysis but undergoes dimerization. If the substrate is methylated prior to reduction, the sulfonium cation is reduced more easily than the neutral substrate to give the same dimeric product. The initially formed dimer (35) eliminates disulfide in an oxidatively induced process during the electrolysis, yielding the final bipyranilidene (36) [110]. 

Nucleophilic substitution by S and Sg (generated electrochemically) at nitrohaloaromatics have been studied, and the mechanism suggested involves Sl and Sg as the active species, and not radical anions. The reaction of sulfur with thiolate ions RS in dimethylacetamide has been studied electrochemically. The reaction leads to the formation of RS, which is then oxidized to RSSR and polysulfide ions. Rate constants for the inter-molecular thiolate/disulfide exchanges, shown in Eq. (33), are much faster ... 

Splitting of the SCN group is not observed and, after the one-electron oxidation, the initial NCSC5H4NO2 anion-radical produces NCSC5H4NO2. The recoveries are close to quantitative disulfides and thiols are not observed. The thiocyanate group (SCN) thus competes less successfully with the nitro group (NO2) for the extra electron than the sulfenyl chloride group (SCI). 

Second, the oxidation of a [l,n]-dithiol by Ti(III)-Fl202 at pH 7 produces the cyclic disulfide as shown in Scheme 3.26. The hnal product of the dithiol oxidation forms a rather stable anion-radical. 

The well-known instability of the disulfide anion radicals, (R SR2)-, is apparently explained by the antibonding electron population, presumably in the framework of the disulfide bond. In some cases, however, these anion radicals turned out to be more or less stable (Breitzer et al. 2001). Two examples in Schemes 3-22 and 3-23 deserve to be distinguished. Firstly, one-electron reduction of naphthalene-1,8-disulfide using sodium in dimethoxyethane generates the corresponding anion radical, Scheme 3-22. Second, the oxidation of a [l,n]-dithiol by Ti(III)-H202 at pH 7 produces the cyclic disulfide according to Scheme 3-23 ... 

For example, the distonic anion radical of cyclopentadienylidene trimethylen-emethane reacts under mass spectrometer gaseous-phase conditions with carbon disulfide by sulfur abstraction and with nitric oxide by NO-radical addition. The first reaction characterizes the distonic anion radical mentioned as a nucleophile bearing a negative charged moiety. The second reaction describes the same anion radical as a species having a group with radical unsaturation (Zhao et al. 1996). 

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