Thiyl radicals mechanism

The key to hexavalent chromium s mutagenicity and possible carcinogenicity is the abiHty of this oxidation state to penetrate the cell membrane. The Cr(VI) Species promotes DNA strand breaks and initiates DNA—DNA and DNA-protein cross-links both in cell cultures and in vivo (105,112,128—130). The mechanism of this genotoxic interaction may be the intercellular reduction of Cr(VI) in close proximity to the nuclear membrane. When in vitro reductions of hexavalent chromium are performed by glutathione, the formation of Cr(V) and glutathione thiyl radicals are observed, and these are beHeved to be responsible for the formation of the DNA cross-links (112). 

The results were interpreted on the basis of a mechanism that starts with the photolytic formation of a radical cage consisting of an aryldiazenyl and and arylthiyl (Ar - S ) radical, followed by diffusion of both radicals out of the cage. Three reactions of the aryldiazenyl radical are assumed to occur bimolecular formation of the azoarene and N2, or of biphenyl and N2 (Scheme 8-37), the monomolecular dediazoniation (Scheme 8-38), and recombination with the thiyl radical accompanied by dediazoniation (Scheme 8-39). In addition, two radicals can react to form a di-phenyldisulfide (Scheme 8-40). 

The low reactivity of alkyl and/or phenyl substituted organosilanes in reduction processes can be ameliorated in the presence of a catalytic amount of alkanethiols. The reaction mechanism is reported in Scheme 5 and shows that alkyl radicals abstract hydrogen from thiols and the resulting thiyl radical abstracts hydrogen from the silane. This procedure, which was coined polarity-reversal catalysis, has been applied to dehalogenation, deoxygenation, and desulfurization reactions.For example, 1-bromoadamantane is quantitatively reduced with 2 equiv of triethylsilane in the presence of a catalytic amount of ferf-dodecanethiol. 

The degradation of tetrachloromethane by a strain of Pseudomonas sp. presents a number of exceptional features. Although was a major product from the metabolism of CCI4, a substantial part of the label was retained in nonvolatile water-soluble residues (Lewis and Crawford 1995). The nature of these was revealed by the isolation of adducts with cysteine and A,A -dimethylethylenediamine, when the intermediates that are formally equivalent to COClj and CSClj were trapped—presumably formed by reaction of the substrate with water and a thiol, respectively. Further examination of this strain classified as Pseudomonas stutzeri strain KC has illuminated novel details of the mechanism. The metabolite pyridine-2,6-dithiocarboxylic acid (Lee et al. 1999) plays a key role in the degradation. Its copper complex produces trichloromethyl and thiyl radicals, and thence the formation of CO2, CS2, and COS (Figure 7.64) (Lewis et al. 2001). 

It has been demonstrated that the MCR enzyme is active only if the metal center of coenzyme F430 is in the Ni1 form.1857 The natural substrate Me-CoM or simple methyl thioethers, however, do not react with Ni1 F430, which has lead to the proposal of a catalytic mechanism in which the addition of a thiyl radical to the S atom of the thioether giving a sulfuranyl radical intermediate is... 

The reaction of P-CAR with thiyl (RS ) and thiyl sulfonyl (RS()2 ) radicals have both been reported using pulse radiolysis (Everett et al. 1995, 1996). It was found that radical addition to P-CAR occurred and that p-CAR scavenges the thiyl radical, including that derived from glutathione, only via this mechanism, whereas it reacts with thiyl sulfonyl radicals by electron transfer as well. 

The half-order of the rate with respect to [02] and the two-term rate law were taken as evidence for a chain mechanism which involves one-electron transfer steps and proceeds via two different reaction paths. The formation of the dimer f(RS)2Cu(p-O2)Cu(RS)2] complex in the initiation phase is the core of the model, as asymmetric dissociation of this species produces two chain carriers. Earlier literature results were contested by rejecting the feasibility of a free-radical mechanism which would imply a redox shuttle between Cu(II) and Cu(I). It was assumed that the substrate remains bonded to the metal center throughout the whole process and the free thiyl radical, RS, does not form during the reaction. It was argued that if free RS radicals formed they would certainly be involved in an almost diffusion-controlled reaction with dioxygen, and the intermediate peroxo species would open alternative reaction paths to generate products other than cystine. This would clearly contradict the noted high selectivity of the autoxidation reaction. 

Rate constants for the reaction of thiyl radicals with the t-BuMePhSiH were also extracted from the kinetic analysis of the thiol-catalysed radical-chain racemization of enantiomerically pure (S)-isomer [34]. Scheme 3.2 shows the reaction mechanism that involves the rapid inversion of silyl radicals together with reactions of interest. The values in cyclohexane solvent at 60 °C are collected in the last column of Table 3.5. 

Conversion of ribonucleotides to deoxyribonucleotides is an important process that occurs by several pathways, and in one of these, tyrosyl radicals 71 are formed, which serve to generate thiyl radicals from cysteine residues (equation A mechanism for this process has been proposed by... 

This reaction is based on a stoichiometric reaction of multifunctional olefins (enes) with thiols. The addition reaction can be initiated thermally, pho-tochemically, and by electron beam and radical or ionic mechanism. Thiyl radicals can be generated by the reaction of an excited carbonyl compound (usually in its triplet state) with a thiol or via radicals, such as benzoyl radicals from a type I photoinitiator, reacting with the thiol. The thiyl radicals add to olefins, and this is the basis of the polymerization process. The addition of a dithiol to a diolefin yields linear polymer, higher-functionality thiols and alkenes form cross-linked systems. 

MECHANISM FIGURE 22-41 Proposed mechanism for ribonucleotide reductase. In the enzyme of . coli and most eukaryotes, the active thiol groups are on the R1 subunit the active-site radical (—X ) is on the R2 subunit and in . coli is probably a thiyl radical of Cys439 (see Fig. 22-40). Steps (T) through are described in the text. 

Carbon monoxide has been used to scavenge OH fonned from the ozonolysis of alkenes. The CO2 tints generated was detected by FTIR spectroscopy and the "OH yields for individual reactions were calculated.239 The significance of the OH-induced intramolecular transformation of glutathione thiyl radicals to a-aminoalkyl radicals has been discussed with respect to its biological implications.240 The kinetics and mechanism of the process indicated that it could be a significant pathway for the selfremoval of glutathione thiyl radicals in vivo. 

When the amino group is fully deprotonated, the rate of the H-transfer is 1.5 x 10s s4, but also around pH 7 the reaction is still fast, at the ms timescale (for a quantum mechanical study see Rauk et al. 2001). Upon the decay of the amnioal-kyl radicals formed in reaction (35) ammonia as formed in a yield that points to disproportionation as the major process (Zhao et al. 1997). The fact that the ami-noalkyl radical is the thermodynamically favored species does not mean that the repair of DNA radicals by GSH (Chap. 12.11) is not due to its action as a thiol. As with many other examples described in this book, the much faster kinetics that lead to a metastable intermediate (here the formation of the thiyl radical) rather than the thermodynamics as determined by the most stable species (here the aminoalkyl radical) determine the pathway the the reaction. In fact, the C-H BDE of the peptide linkage is lower than the S-H BDE and repair of DNA radicals by peptides, e.g., proteins would be thermodynamically favored over a repair by thiols but this reaction is retarded kinetically (Reid et al. 2003a,b). 

Sprinz H, Schwinn J, Naumov S, Brede O (2000) Mechanism of thiyl radical-catalyzed isomerization of unsaturated fatty acids in homogeneous solution and in liposomes. Biochim Biophys Acta 1483 91-100... 

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. 

The addition of thiols to olefins (thiolene reaction), to form thioethers, is a well-known reaction. The process can occur by either free-radical or ionic mechanisms. The free-radical reaction can be initiated thermally via a peroxide or by UV irradiation with benzophenone. The initiation step involves the formation of a thiyl radical by hydrogen atom abstraction. Both of these species are capable of starting polymer chains (Table 2.30). 

At present the exact details of the mechanisms leading to each of the products are far from well understood (7.81. However, it seems likely that oxidation of the common naturally-occurring organo-sulfur compounds (dimethyl sulfide, methyl mercaptan and dimethyl disulfide) proceeds, at least in part, through formation of the methyl thiyl radical, CHjS (4.9-111. That is the main reason for carrying out direct studies on CH3S radical reactions where the individual reactions are isolated. 

The activation energy of the reaction and pre-exponential factor were determined to be 16.5 kcal/mole and 1010 s-1 respectively. Reaction mechanisms involving the formation and dimerization of thiyl radicals (RS-) were utilized to explain the kinetic data. The active species in such mechanisms is the thiolate anion which is formed in a reversible step with the base catalyst (59). The resulting anion supposedly reacts with 02 via an electron transfer mechanism to give peroxide ion ... 

When attention was turned to Sh2 attack at Pt(II) involving thiyl radicals, a different situation was encountered (29, 142), as summarized in Scheme 4 and by the following chain mechanism ... 

The P-cleavage of halogen atoms and thiyl radicals from biradicals appears to follow a simple enough mechanism, as shown in Sch. 2. After being formed, the 5-substituted 1,4-biradical can undergo radical cleavage in competition with its normal decay reactions. That leaves an... 

Of direct relevance to the debate described above, Skidmore examined extensively the mechanism of polarity reversal catalysis described in Scheme 11 and concluded that the key step (step 2, Scheme 11) in the proposed mechanism, namely the transfer of hydrogen atom from a trialkylsilane to a thiyl radical, is severely endothermic54,55. 

The inefficient trapping of thiyl radicals by dodecene-1 was attributed to the effective interception of the radicals by Mn(III), resulting in electron transfer oxidation to the thioxonium ion. By contrast, thiyl radicals formed in the oxidation of thiols by the weaker oxidant, ferric octanoate, were scavenged by dodecene-1. Disulfide was formed by dimerization of thiyl radicals.352 Thus, the mechanism for disulfide formation is dependent on the nature of the metal oxidant. 

On the other hand, unsaturated lipids may act as secondary mediators of the MnP/Mn system, in a mechanism known as lipid peroxidation, which is a free radical chain-reaction proceeding via the oxidation of unsaturated lipids [32, 33]. Thiols may also undergo oxidation by MnP/Mn and produce thiyl radicals, which in turn mediate in the oxidation of a variety of compounds [34]. 

There are a number of mechanisms by which ascorbate may facilitate the removal of activated oxygen-derived molecules in vivo-, these include reaction with 0 2, HOj and OH , as well as the reduction of thiyl radicals (see section 5.1),... 

Because reaction of thiyl radicals with 02 is known to form sulfinyl radicals (95), mechanisms involving radicals were also considered. Although such a mechanism would have the correct stoichiometry and account for the lack of scrambling in the studies involving labeled 02, reactions involving the formation of free radicals were ruled out because... 

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