Sulphur-centred radicals

A detailed study by ESR of the arenesulphonyl radicals 1 has been reported following the irradiation of the corresponding chlorides in toluene9. The spin distribution in the radicals was determined as was the rotation around the S—C aryl bond. A similar study was performed using the sulphonamidyl chlorides 2. This clearly showed that the radical was still sulphur-centred and that there was little interaction with the adjacent nitrogen10. A review of the reactivity and the formation of sulphur-centred radicals has been published11. 

Oxidation by [Cr(en)2(maa)]+ (maa = mercaptoacetate2 ) by OH at pH 5—10 proceeds by two parallel pathways. Abstraction of a hydrogen atom from the -carbon by OH produces a transient absorbing at 410 nm and leads to oxidation at the carbon centre. The other pathway leads to oxidation at sulphur and involves addition of OH to the sulphur to form a transient absorbing at 345 nm. This species subsequently dimerizes with a rate constant of 9.3 x 10 1 mol s at 24 °C. Oxidation of [Cr(en)2(maa)]+ by Np i and Co in acid solution involves reaction at the carbon centre only. It is suggested that the high acidity and the low concentrations of any sulphur-centred radicals produced in these reactions might favour conversion into the carbon-centred species. 

Ring expansion of the sulphonamide reaction199 (equation 144) demonstrates the ability of a ruptured sulphur-centred free radical to undergo 1,3-Fries type migration200 (equation 145). Sulphur dioxide extrusion may also provide a synthetic route to fi-lactams201 (equation 146). 

Methionine (Met) is one of the sensitive sulphur-containing amino-acids toward one-electron oxidation. However its ease of oxidation is also modulated by the structure. The one-electron oxidation of Met in peptides yields sulfide methionine radical cations (MetS +) which convert into intermediates that obtain catalytic support from neighbouring groups containing electron rich heteroatoms (S, N, O) and thus stabilize electron deficient sulphur centres in S.-.S, S.-.N, and S.-.O-three-electron bonded complexes (Fig. 5) [11]. 

Moreover, formation of radical transients with S.-.O bonds is kinetically preferred, but on longer time scale they convert into transients with S.-.N bonds in a pH dependent manner. Ultimately transients with S.-.N bonds transform intramolecularly into C-centred radicals located on the C moiety of the peptide backbone. Another type of C-centred radicals located in the side chain of Met-residue, a-(aikylthio)alkyl radicals, are formed via deprotonation of MetS +. C-centred radicals are precursors for peroxyl radicals (ROO ) that might be involved in chain reactions of peptide and/or protein oxidation. Stabilization of MetS +through formation of S.-.O- and S.-.N-bonded radicals might potentially accelerate oxidation and autooxidation processes of Met in peptides and proteins. Considering that methionine sulfoxide, which is the final product coming from all radicals centred on sulphur, is restored by the enzyme methionine sulfoxide reductase into MetS, stabilization of MetS +appears as a protection against an eventual peroxidation chain that would develop from a carbon centred radical. 

The radical cation of cysteine, Cys, serves as an example of the first and third point.This amino acid contains two potential donor sites, sulphur and nitrogen, so electron transfer to an excited sensitizer could result in a sulphur-centred or a nitrogen-centred radical cation. Decarboxylation of Cys to give an a-amino alkyl radical occurs on a timescale slightly faster than 1 ns, so a direct observation by EPR is not feasible. However, the CIDNP spectrum with 4-carboxybenzophenone CB as the sensitizer exhibits polarizations of the starting amino acid, which can only be the product of reverse electron transfer of pairs Cys " CB but obviously not in any way the product of the radical pairs formed by the decarboxylation. Concentrating on the cysteine polarizations thus avoids all complication due to the rich secondary chemistry. ... 

Because it is well established that radical cations of monoamines and monosulphides have substantial h)q5erfine couplings only for the protons at carbon atoms adjacent to the radical centre, " nitrogen-centred Cys can develop polarizations only for of the substrate, while sulphur-centred Cys must cause both... 

Figure 19 Polarization pattern in the photoreaction of S-ethylcysteine Cys with 4-carboxybenzo-phenone at pH 77. Bottom trace spectrum in the dark top trace photo-CIDNP spectrum. The assignment of the resonances refers to the formula given at the top. The a proton is unpolarized, the p and y protons are polarized, so the radical cation is seen to be sulphur-centred. Further explanation, see text.

The complex photochemistry of cysteine derivatives sensitized by 4-carboxy-benzophenone 15 has been unravelled by CIDNP. The initially formed sulphur-centred (see. Figure 19) radical decarboxylates rapidly to give an a-amino alkyl radical, which in turn cleaves into a thiyl radical R-S and a vinylamine in competition with being oxidized to an imine by surplus sensitizer all these resulting species are unstable themselves and undergo further reactions. The rates of the radical fragmentations and the radical oxidation were obtained from the CIDNP experiments. 

Among the various free radicals that can exist in proteins, the sulphur-centred ones coming from disulfide bonds and/or thiol function, are of major importance. First, they take part in enzyme catalysis (9). Second, they are involved in a variety of key metabolic processes like those involving glutathione and thioredoxin. The repair reaction (reaction (1)) was proposed to be a mechanism explaining the protective effect of thiol molecules toward e. g. DNA in all events related to free radical production including radiobiology (7, 131). 

This suggested that the Complex I generator as in the case of rats and pigeons (Herrero and Barja 1997), can be the Complex I iron-sulphur centres. Complex III also generated free radicals in the three species studied by Herrero and Barja (1998). 

Dunster, C., and Willson, R. L., 1990, Thiyl free radicals Electron transfer, addition or hydrogen abstraction reactions in chemistry and biology, and the catalytic role of sulphur compounds, in Sulphur-centred Reactive Intermediates in Chemistry and Biology (C. Chatgilialoglu and K. D. Asmus, eds.), pp. 377-387, NATO-ASI Series, Life Sciences, Plenum Press, New York. 

The tripeptide nature of glutathione introduces a complication not seen with some simpler thiols. The glutamyl moiety has an electron-donating amino substituent which, when deprotonated, renders the hydrogen on the substituted carbon liable to abstraction by oxidizing agents. The sulphur-centred thiyl radical is reactive towards activated C-H bonds, as noted above (reaction (Ir)), and can abstract intramolecularly from this activated carbon if the amino substituent is deprotonated. The intramolecular rearrangement is thus base catalysed and can be represented by ... 

It may appear rather strange to measure a strictly inorganic compound. However, there is one important correlation to biopolymers. In proteins the polypeptide chain imposes considerable strain on metal-sulphur binding centres which may lead to sulphur radical species. Such species have been discussed for cytochrome c oxidase and plastocyanin Likewise the polysilicates could take over the same role. They are capable to polarize the sulphur species and the existence of sulphur radicals are debated. 

A number of heterocyclic S—N ambident anions have also been shown to react via the sulphur atom with 2-halo-2-nitropropanes by the S l mechanism5,116. The authors suggest116 that the addition of ambident anions to alkylnitro radicals (CR2N02) takes place under kinetic control via the more nucleophilic centre. 

Addition reactions of sulphenyl halides (in particular chlorides) to acetylene derivatives have been extensively explored and recently reviewed (Modena and Scorrano, 1968). Although free radical processes may be involved under specific conditions, the addition of both arene-and alkanesulphenyl halides normally occurs by an ionic mechanism, the sulphenyl halide sulphur being the electrophilic centre. 

The proposed catalytic mechanism of the ferredoxin oxidoreductase [32] is shown in Fig. 4, a similar mechanism existing for the analogous citric acid cycle enzyme, 2-oxoglutarate oxidoreductase. In outline, the 2-oxoacid is decarboxylated in a TPP-dependent reaction to give an hydroxyalkyl-TPP. From this, one electron is abstracted and transferred to the enzyme-bound iron-sulphur cluster, generating a free-radical-TPP species. This intermediate can then interact direct with coenzyme-A to form acyl-CoA, the iron-cluster receiving the second electron. In each case, ferredoxin serves to re-oxidise the enzyme s redox centre. 

The oxidation of sulphur dioxide on carbon also appears to be controlled by complexes on the surface. Siedlewski has shown that carbon pretreated with oxygen is a more active catalyst than without. Oxygen adsorption involves surface free radicals and electrons with unpaired) spins are active centres for sulphur dioxide adsorption, suggesting that some kind of oxidation-reduction cycle involving surface complexes may be important. 

Molybdenum dialkyldithiocarbamates Molybdenum dialkyldithiocarbamates are multifunctional lubricant additives as anti-wear, anti-friction and antioxidants. Molybdenum dialkyldithiocarbamates are also multifunctional antioxidants due to the hydroperoxide decomposing ability of dialkyldithiocarbamates, see Section 4.4.2, and the radical scavenging capacity of molybdenum. The best established structure for molybdenum dialkyldithiocarbamates is a six-coordinate complex of a dinuclear molybdenum centre with each molybdenum bonded to terminal oxygen or sulphur atoms, two bridging oxygen or sulphur atoms and one dialkyldithiocar-bamate ligand. Fig. 4.6 [44] ... 

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