Thiyl/disulfide radical anion

Before proceeding to describe the mechanistic features of disulfide reduction, it is useful to first describe the effect of substituents on the stability of thiyl radicals and disulfide radical anions as well as the consequences, from a theoretical viewpoint, of the unpaired electron on both the bond energy and the S—S bond length of disulfides. 

An H-transfer may also occurs intramolecularly such as in DDT via a five-membered transition state [reaction (33) Akhlaq and von Sonntag 1986]. In the given case, an H2S forming chain reaction is induced [cf. reaction (34) followed by the (slow) H-abstraction of the thus-formed radical from DTT] which comes to a halt when the thiyl radical is complexed as the disulfide radical anion at higher pH values [cf. reaction (40)]. 

Sulfur free-radical chemistry is largely governed by the ability of sulfur to form three-electron bonded intermediates. A case in point is the complexation of a thiyl radical with a thiolate ion (for an analogy with the halide and other pseudohalide systems, see Chap. 5.2). These disulfide radical anions are characterized by strong absorptions in the UV-Vis (Adams et al. 1967). Complexation can occur both intermolecularly as well as intramolecularly. For GSH, for example, the stability constant of the disulfide radical anion is 2900 dm3 mol1 (Mezyk 1996a). The protonated disulfide radical anion is not stable, but such intermediates are known in the cases of the intramolecular complexes [reactions (39) and (40) Akhlaq and von Sonntag 1987]. 

The electrophilic nature of thiyl radicals expresses itself also in a pronounced tendency to couple the unpaired electron at sulfur with free electron pairs of another heteroatom. The most prominent example is the reaction of thiyl with thiolate and the establishment of an equilibrium with disulfide radical anions, formulated in eq. 26. 

The actual electronic structure of (RSSR) is especially interesting. Key feature is a 2o/10 bond between the two sulfur atoms, rendering [RS.. SR]-an even more appropriate and informative notation.55,56 While further details on this three-electron bond will be dealt with in the odd electron bonds section vide infra), the following is of immediate interest. The combined effect of the two bonding o-electrons and the one antibonding a electron affords a formal bond order of 1/2. This, in turn, provides the rationale for the above equilibrium and relative ease of redissociation of the newly formed sulfur-sulfur bond. The same [RS. . SR] species is, incidentally, formed in the reduction of disulfides by hydrated electrons. Thiyl radicals and disulfide radical anions thus are two conjugate forms of the one-electron redox intermediate between thiols and disulfides. 

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... 

The formation and properties of thiyl radicals and disulfide radical anions will be dealt with together. As will be seen, they are closely related to each other... 

Although the outcome on the product side is eventually the same, whether or not a transitory adduct intermediate is formed, the kinetics of the thiyl radical formation are certainly affected. Experimental verification of the suggested adduct intermediate is, however, still pending. In fact, even positive identification of the adduct would not prove reaction sequence (16) and (17). Only if the disulfide radical anion (or its decay product RS ) and the molecular products are also known can this mechanism be distinguished from possible competing displacement according to reaction (5), since the latter process may proceed via an adduct as well. 

PHYSICOCHEMICAL PROPERTIES AND DETECTION OF THIYL RADICALS AND DISULFIDE RADICAL ANIONS... 

Other prominent sites for electrophilic addition are non-bonding electron pairs as they are present in many heteroatom-containing organic molecules. One example has already been mentioned, namely the RS conjugation with the sulfur anion function in thiolate. As formulated in the back reaction of equilibrium (14) this yields the three-electron bonded disulfide radical anion, (RS SR)in which the unpaired thiyl electron couples with the free p-electron pair at the thiolate sulfur. In this context, a significant consequence emerges with respect to the overall redox properties of such a system. As has been stated already, the... 

In simple aliphatic systems this protonated form of the disulfide radical anion is usually not detectable because of its fast decay into freely diffusible thiyl and thiol components, reaction (32) ... 

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] ... 

Thermal production of RSS from thiyl radicals and disulfide radical anions, possibly through RSS(H)R adducts is quite a common phenomenon in both glasses and crystalline solids [30, 31]. The case when it was not observed is represented by an intramolecular RSS(H)R adduct formed from 1,3-propanedithiol in organic glasses [95]. The cyclic structure of this adduct was suggested to increase the activation barrier required for the concerted process. In contrast, there are only a few examples when such a process is involved in liquid solutions. Fast back dissociation of RSS(H)R adducts is likely to be the process that effectively competes with RSS formation making the latter process observable only in a few cases [97, 98]. 

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... 

The stability of radical anions of disulfides [RS—SR] and their ease of dissociation into thiolate anions and thiyl radical were studied as a function of pH with alkyl substituents of different structures ... 

It is easy to recognise that the reductive cleavage, forming freely diffusing thiyl radicals, is not possible when the disulfide bridge is held together by a linking backbone as, for example, in lipoic acid and several cyclic disulfides. Reduction of these compounds have been examined extensively and lifetimes of over lOOps have been measured for the 2c/3e bonded radical anion, even in the absence of free thiolate [14, 28-31]. Here, as depicted schematically in equation (15) the thiyl and thiolate components are prevented from free diffusion and, therefore, the back reaction of the equilibrium will be much faster and more efficient than in the non-linked systems. 

PCP-phenolic radical that possesses an absorption spectrum in H2O at 440 nm and decays via second-order kineties with k = 9. x 10 /M/s, as evidenced by pulse radiolytie studies. The PCP-phenolic radical can attach covalently to the C8-site of dG to generate the C8-OPCP adductIn the presence of GSH, redox cyeling of the phenoxyl radieal with thiyl radieal generation will yield a GSH disulfide anion radieal that ean reduetively aetivate O2 to generate the superoxide radieal anion (02 ) that ean generate free ferrous iron Free Fe " " may... 

Surdhar PS, Armstrong DA. 1987. Reduction potentials and exchange reactions of thiyl radicals and disulfide anion radicals. J Phys Chem 91 6532-6537. 

In the initially proposed mechanism, the intermediate 2-nitro-2-propyl radicals, Me2(N02)C, undergo two reactions with the more basic (nucleophilic) thiolates addition of thiolates leading to SRN1 products (Equation 10.20 in Scheme 10.32), and SET to yield the nitro anion and thiyl radicals (RS ), Equation 10.21, which combine to give disulfide. 

A similar, but bimolecular, photoinduced reaction was observed on the basis of the nickel complex (28), p-toluene thiolate, and thioanisole reactants to generate methane and disulfide. The thiyl radical and Ni(I) complex was prepared by the photolysis of the Ni(II) complex (28) and j -toluene-thiolate anion in acetonitrile solution. Upon irradiation (A, = 350 nm) of the mixture of complex (28), j -toluene-thiolate ion, and thioanisole in acetonitrile under argon, gas chromatography-mass spectral analysis showed the formation of methane, ditolyl disulfide (TolS)2, and a mixed disulfide TolSSPh. The proposed catalytic mechanism is depicted in... 

As shown in Scheme 8.4, the resulting disulfide anion radical dissociates into a thiolate ion R-S and a thiyl radical R-S. Proton transfer from the tryptophan cation radical to the thiolate ion leads to the tryptophan radical Trp and the thiol RSH. The final stage of the process is governed by radical coupling, which may result in sulfenylation of the Trp moiety yielding Trp-S-R, or in inter-molecular cross-linking, i.e. in the formation of enzyme dimers or trimers. 

The reduction potentials of thiyl radicals and disulfide aniones in Table 7 are of interest because of the importance of sulfhydryls in biological systems and the involvement of glutathione (GSH) as a cellular protective agent [72]. Of primary... 

The existence of this thiol ionization equilibrium means that the RS radical reduction potential is pH dependent at pHs up to the which is near 8 to 10 for aliphatic thiols and 6 to 7 for aromatic ones. In addition to this, alipahtic thiyl radicals form disulfide anion radicals with the parent anions in equilibrium (25) ... 

Structural properties of several kinds of sulfur-centered radical have been discussed in excellent reviews [1-5]. The reader is referred to those references for studies up to 1993. The present article will concentrate on work appearing since those publications and on aspects not covered in them. The discussion includes S, S " and S2 ", alkyl thiyl and perthiyl radicals, alkyl sulfide and disulfide cation radicals, and disulfide anion radicals. The corresponding aryl thiyl species are also discussed where information is available. Attention is also paid to structures with two center-three electron 2(t/ (t bonds. Structures of alkyl sulfoxyl radicals are considered in Chapter 8. 

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