Sulfide Radical Cations

The ion-molecule reaction between thiirane and its radical cation to form a thiirane sulfide radical cation and ethylene has been studied by Qin, Meng and WiUiams [134]. ESR studies using a low-temperature sohd-state Freon radiolysis technique provided compeUing evidence that the hemibonded dimer radical cation of thiirane is an intermediate in this so-called sulfur-transfer reaction see Scheme 2. 

In addition to the complexation by the parent, the sulfide radical cation can undergo a deprotonation at a neighboring carbon [cf. reaction (51)]. Also, in the case of thiourea, deprotonation at nitrogen in basic solution competes with a complexation by the parent (Wang et al. 1999). This reaction is, of course, not given by its jV,jV,jV, N -(etramethyl derivative. 

Armstrong D, Sun Q, Schuler RH (1996) Reduction potentials and kinetics of electron transfer reactions of phenylthiyl radicals comparisons with phenoxyl radicals. J Phys Chem 100 9892-9899 Asmus K-D (1979) Stabilization of oxidized sulfur centers in organic sulfides. Radical cations and odd-electron sulfur-sulfur bonds. Acc Chem Res 12 436-442 Asmus K-D (1990a) Sulfur-centered free radicals. Methods Enzymol 186 168-180 Asmus K-D (1990b) Sulfur-centered three-electron bonded radical species. In Chatgilialoglu C, Asmus K-D (eds) Sulfur-centered reactive intermediates in chemistry and biology. Plenum, New York, pp 155-172... 

Bonifacic M, Schafer K, Mockel H, Asmus K-D (1975b) Primary steps in the reactions of organic disulfides with hydroxyl radicals in aqueous solution. J Phys Chem 79 1496-1502 Bonifacic M, Armstrong DA, Carmichael I, Asmus K-D (2000a) p-Fragmentation and other reactions involving aminyl radicals from amino acids. J Phys Chem B 104 643-649 Bonifacic M, Hug GL, Schoneich C (2000b) Kinetics of the reactions between sulfide radical cation complexes,[S.. S]+ and [S. N]+, and superoxide or carbon dioxide radical anions. J Phys Chem A 104 1240-1245... 

K.-D. Asmus, Acc. Chem. Res., 12, 436 (1979). Stabilization of Oxidized Sulfur Centers in Organic Sulfides. Radical Cations and Odd-Electron Sulfur-Sulfur Bonds. 

A quantum-chemical interpretation of the MS fragmentation of organic molecules has been reported <1987CHE512>. Based on the bond orders, the weakest bond is the C(3)-C(4) bond and hence should fragment first and to a much greater extent than the S-C or the C(2)-C(3) bond. This then forms the divinyl sulfide radical cation which cyclizes to intermediate 94 and then eliminates acetylene to form thiirene 93 (Figure 16). On the other hand, it is also possible that the bicyclic intermediate 95 is formed first, which could fragment to form radical cation 96 and/or intermediate 94 both of which lose acetylene to form thiirene 93. 

Stabilization of sulfide radical cations with N- and 0-atoms of peptide bonds... 

As it has been already mentioned vide Sec. 3.3), neighboring groups containing electron-rich heteroatoms play a significant role during the one-electron oxidation since they stabilize the forming sulfide radical cations. In oligopeptides, very often heteroatoms in peptide bonds are the only nucleophiles present in the vicinity of the sulfide radical cation site Met(S ). 

Reactions of sulfide radical cation complexes with Of... 

The reactions of superoxide radical anions (O2") with sulfide radical cation complexes might represent an important and efficient reaction pathway for the formation of sulfoxides in peptides and proteins containing methionine residues. Absolute rate constants for two sulfide radical cation complexes (S..S) from 1,5-dithia-3-hydroxycyclooctane and (S..N) from Met-Gly dipeptide with Of were measured using pulse radiolysis. The rate constant for the... 

This drop in reactivity may, in part, reflect the lower probability of Oj" to encounter S atom in the (S..N) complex as compared to the symmetrical (S.. S) complex. It is important to note that the reactions of Oj with the sulfide radical cation complexes proceed 2.5- to 8-fold faster than the reaction of O2" with superoxide dismu-tase k 2 X 10 dm moHs" ). From a biological point of view, it means that sulfide radical cation-O " reactions might represent a potential source for sulfoxide formation when the system is exposed to high concentrations of reactive oxygen species. 

Baciocchi E, Gerini ME. (2004) Rotational barriers, charges, and spin densities in alkyl aryl sulfide radical cations Density functional study. J Phys Chem A 108 2332-2338... 

Bobrowski K, Hug GL, Pogock D, Marciniak B, Schoneich C. (2007) Stabilization of sulfide radical cations through complexation with the peptide bond Mechanisms relevant to oxidation of proteins containing multiple methionine residues. J Phys Chem Sill 9608-9620. 

Hug GL, Bobrowski K, Pogocki D, Horner G, Marciniak B. (2007) Conformational influence on the type of stabilization of sulfide radical cations in cyclic peptides. Chem Phys Chem 8 2202-2210. 

Bonifadc M, Hug GL, Schoneich C. (2000) Kinetics of the reactions between sulfide radical cation complexes, [S.. S] and [S.. N], and superoxide or carbon dioxide radical zmons. J Phys Chem A 104 1240-1245. 

Methionine. The reaction of superoxide radical anions (02 with sulfide radical cation-nucleophile complexes might represent an efficient sulfoxide-forming process in peptides and proteins containing methionine under conditions where significant amounts of sulfide radical cation complexes and superoxide are formed simultaneously. The rate constant for the reaction of 02 with the (S.-. N)+ complex was found to be ca. 3-fold slower as compared to that ofthe reaction with the (S.-.Sf complex. This drop in reactivity may, in part, reflect the lower probability of 62 to encounter S-atom in the (S.-.N) complex as... 

This section will mainly focus on two biologically relevant sulfur-centered radical species, thiyl radicals (RS ) and sulfide radical cations (R2S +). 

The one-electron oxidation of organic sulfides yields sulfide radicals cations (Reaction (3.36)) [104]. 

In general, sulfide radical cations would either deprotonate in the a-position to the sulfur, yielding a-(alkylthio)alkyl radicals, or engage in the one-electron oxidation of additional substrates. However, recent hypothesis and results have focused on a possible role of methionine sulfide radical cations in hydrogen abstraction reactions within the Alzheimer s disease yS-amyloid peptide (ySAP) [73]. These mechanisms will be discussed here in some detail. 

Scheme 3.6. The proposed hydrogen abstraction by (S.. O) three-electron-bonded Met sulfide radical cation from Gly.

Diphenyl sulfide radical cation has been reported [116] to absorb in the visible with = 780 nm for the species formed by gamma radiolysis of Ph2S in 1,2-dichloroethane at 77 K. Laser flash photolysis of 46 in acetonitrile provides Ph2Ss which shows absorption bands at 330 and 750 nm [117]. 

In addition to 7r-delocalization of alkyl aryl sulfide radical cations, other possibilities exist for stabilization of the radical cation if there are electron-rich groups with unpaired electrons ortho to the sulfur atom. Because of the importance of these possibilities, they will be discussed in detail. The radical cation of 49a may prefer a two-center, three-electron (2c, 3e) bond between the two sulfur atoms as illustrated in 50 rather than 7r-delocalization. 

Dialkyl sulfide radical cations have been made from the parent sulfides by a variety of methods including y-radiolysis in matrices at low temperature [280], pulse radiolysis [281-285], photoinduced electron-transfer [286], mass spectroscopic methods [287,288], electrochemical oxidation, and by oxidation with one-electron chemical oxidants. A brief overview of these methods will be presented here even though most of these methods have already been mentioned previously in this review. 

Table 10. EPR Spectroscopic parameters for dialkyl sulfide radical cations... 

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