Thiols radicals

Synthesis of heterocycles by forming C—X bonds by radical reactions is not a generally applicable method, and seems not to be useful for making small rings. However, the attack of thiol radicals on double bonds can be a practical synthetic route, such as in the conversion of 1-hexene-7-thiol to thiepane (Section 5.17.3.3.1). 

The stability of chalconide (ionic) compounds decreases from oxygen to tellurium treatment with water produces XH- with X = O or S (hydroxyl and thiol radicals, respectively), but XH2 with X = Se or Te. On warming, aqueous solutions of HS evolve hydrogen sulfide, evidencing that the hydrosulfide ion is much less stable than hydroxide. 

Nitrosothiols should not bind directly to the heme of guanylate cyclase, but rather to activate guanylate cyclase by releasing nitric oxide. The simple cleavage of nitrosothiols into nitric oxide and a thiol radical is energetically expensive, so the activation may involve an oxidation with a second thiol group. 

For substituted tricyclo[4.1.0.02,7]heptanes, similar addition of benzenethiol in diethyl ether gave an isomeric mixture of bicyclo[3.1.1]heptanes.35 As shown in the mechanistic scheme, the 1,3-disubstituted patterns of the bicyclo[3.1, l]heptanes are governed by the regiospecific attack of the thiol radical on the sterieally less hindered bridgehead carbon. The results of these radical additions arc summarized for bicyclo[n.l.l]alkanes (Table 8)35 and bicyclo[1.1.0]butanes (Table 9). 

Until recently, the mechanism of the inhibition of light-induced yellowing was subject to speculation. However, solid state ESR and CIDEP have provided insight into the mode of inhibition by thiols (Wan, J.K.S., et al, J. Wood Chem. Technol., in press). Near-uv irradiation of unbleached and peroxide bleached thermomechanical pulp impregnated with thiols caused a rapid increase of the thiol radicals. The time resolved CIDEP spectrum, however, shows a symmetric broad band characteristic of the polarized phenoxy radical. This result suggests that thiols quench triplet generated phenoxy radicals in a secondary thermal process. 

In the case of R4 = phenyl and R3 = H, all the compounds investigated eliminate a phenylketene molecule and the fragment ion 57 formed, then lose a thiol radical to give the cation 58 (Equation 5), which is also formed by loss of phenylketene and a thiol radical from the molecular ion <2005PS2779>. 

After abstraction of hydrogen from the thiol group by a growing chain radical, the chain is terminated under simultaneous generation of a thiol radical ... 

RNRs catalyze the reduction of ribonucleotides to deoxyribonucleotides, which represents the first committed step in DNA biosynthesis and repair.These enzymes are therefore required for all known life forms. Three classes of RNRs have been identified, all of which turn out to be metalloenzymes. The so-called class I RNRs contain a diiron site (see Cobalt Bn Enzymes Coenzymes and Iron-Sulfur Proteins for the other two types of RNRs). As diagrammed in Figure 5, these enzymes generate first a tyrosyl radical proximal to the diiron site in the protein subunit labeled R2, and then a thiyl radical in an adjacent subunit (Rl) that ultimately abstracts a hydrogen atom from the ribonucleotide substrate. This controlled tyrosine/thiol radical transfer must occur over an estimated distance of 35 A, and a highly choreographed proton-coupled electron transfer (PCET) mechanism across intervening aromatic residues has been proposed. Perhaps, even more remarkably,... 

Hermann R, Dey GR, Naumov S, Brede O. (2000) Thiol radical cations and thiyl radicals as direct products of the free electron transfer from aromatic thiols to -butyl chloride radical cations. Phys Chem Chem Phys 2 1213-1220. 

The C=C bonds in sulfamoyl-protected imidazoles 765, 767 are electrophilic in nature and can be functionalized either through thiol radical addition 766 or palladium-catalyzed hydride reduction 768 (Scheme 187) <2005HCA707>. In the case of 768, both C=C and C=0 functions are reduced. 

An organic disulfide sorbed into a transition-metal form of a zeolite may dissociate to give two thiol radicals. These may coordinate to cations by a mechanism which involves electron sharing or electron transfer, for example to oxidize the cation fiorther and to generate coordinated organic sulfide ions. This was observed with dimethyldisulfide sorbed into Co -exchanged zeolite... 

No successful attempts to observe the spectrum of the thiophenoxy radical or its unhindered substituted analogues have been reported in solution studies. Smentowski (1963) found that the p-chlorobenzene-thiolate anion reacts with nitrosobenzene to give the spectrum of the latter s radical-anion (flow system) and a high yield of the disulphide thep-chlorothiophenoxy radical is apparently formed as an intermediate but dimerizes too rapidly for spectroscopic detection. The spectra of both aromatic and aliphatic thiol radicals have, however, been observed when the species, generated by ultraviolet irradiation of the corresponding disulphides, are trapped in the solid state (Smissman and Sorensen, 1965 Windle et al., 1964). 

P. aeruginosa azurin retains voltammetric interfacial electron transfer function in the adsorbed state. This is notable as the protein structure is almost certain to be modified on adsorption via the surface disulfide bond. Disulfide bond breaking followed by Au-S bond formation is thus a likely adsorption scenario, but re-assembly of the protein structure via Au-S bond formation to the liberated thiol radicals is unlikely to recover the exact native structure. 

Excited-state porphyrins also are good oxidants. Photoreduction of uroporphyrin by EDTA and other electron donors [89] gives ESR spectra of the porphyrin radical anion, which has a low g value (2.002) and a broad ESR line (5 G) with no resolved hyperfine structure. The radical is transient and decays with second-order kinetics in aqueous solutions. Similar spectra have been reported from hematoporphyrin irradiated in the presence of thiols [88]. In addition, a thiol-derived radical was spin-trapped by MNP. The hematoporphyrin radical anion itself is not spin-trapped, but it will transfer an electron to MNP to form Bu NHO. With reducing agents other than thiols, radicals from the reducing agent (ascorbate, catechols, p-phenylenediamine) were detected directly [88]. 

RS + o2 — RS° + 02 Two thiol radicals then recombine to form a disulfide ... 

The reaction mechanisms have been explored in the coumarin, ketocoumarin, or titanocene derivative/bis-aryl imidazole Cl-HABPmercaptobenzoxazole system [240]. For example (10.67), when the sensitizer is the coumarin Cl, an electron transfer occurs and the formed Cl-HABI radical anion leads to a lophyl radical that undergoes a hydrogen transfer with the thiol SH (the lophyl radical anion reacts with the thiol radical cation). The Cl/SH interaction can also participate in the initiation process. The role of new thiols and disulfides has been recently studied [241]. 

Silverman and Zieske have rationalized how a protein nucleophile other than flavin is involved in MAO inactivation reactions, and why different inactivator compounds specifically react with flavin, protein amino acids, or both (100). Hydrogen atom donation from a cysteine residue to the flavin semiquinone radical would produce a thiyl radical, which could then capture the primary or secondary alkyl radical generated on cyclopropyl ring opening from the amine radical cation of the inactivator. The hydrogen atom abstraction reaction between the flavin and active site amino acid may be an equilibrium process such that either species could be present at any turnover. Hence, a combination of steric constraints and proximity to either the flavin semiquinone radical or the thiol radical will determine the site of adduct formation for a particular inactivator structure. A two-dimensional representation is shown in Scheme 23 (compounds 40-42), which illustrates the proposed equilibrium between the flavin semiquinone radical and amino acid as well as the proposed intermediates for the inactivation of MAO by A-(l-methylcyclopropyl)benzylamine 40 (104), rrradical center relative to the particular protein radical is consistent with proposed site of attachment of inactivator to protein 40 is near the flavin radical, such that exclusive flavin attachment occurs, 41 is positioned closer to the amino... 

The product was previously identified in beer by Andrews (1987) and in human sweat by Polak et al. (1988), and characterized as sunstruck or lightstruck off-flavor. The cause has been attributed to the degradation of bitter isohumulones from hops under the influence of ultraviolet light (Bondeel et al., 1987). By photofragmentation trans-isohumulone liberates a prenyl radical which can trap a thiol radical, producing an undesired flavor for beer. Holscher et al. (1992) have also shown that 3-methyl-2-buten-l-thiol and 3-mercapto-3-methylbutanol are principally formed under pyrolytic conditions in roast model reactions of prenyl alcohol and sulfur-containing amino acids. 

E. Strauss, Thiols, Radicals and Antibiotics Mechanistic Studies in Coenzyme A Biosynthesis. Ph.D. Dissertation, Cornell University, Ithaca, NY, 2003. 

The formation of C-S bonds by thiol radical additions to unsaturated sugars has also been reported, such as the addition of thiolacetic acid to glycal 167 [111]. Giese... 

Thiohydroxamic esters, such as V-hydrox5q)5nidine-2-thione, were first used as free radical precursors by Barton. " The decomposition of such esters by heat or visible light yields acyloxy radicals and pyridine thiol radicals. However, on irradiation at low-temperature, the chain reaction is essentially suppressed. 

Stevens et al. have proposed another likely mechanism for the Jacobson synthesis where a single-electron transfer process appears to operate. Here thiobenzamide reacts with the base to generate thiolate ion that undergoes oxidation to form a thiol radical shown below. The thiol radical can attack the unsubstituted ortho position and form a five-membered ring that aromatizes through the elimination of a hydrogen radical and form benzothiazole. Stevens et al. during this study also noted that the availability... 

Polymers prepared by RAFT can also be end-fiinctionalized by transformation of the labile C-S bond at the co-chain end by several methods including reaction with nucleophiles to form the corresponding thiol, radical-induced reaaions, and thermal elimination (Scheme 32). " ... 

Figure 9 Plots of tan 5 as a function of temperature. In sample a, trifunctional thiol small molecules and trifunctional vinyl ether small molecules are mixed in the ratio 1 1, allowing for only thiol-ene reaction. In samples b-j, polymeric diacrylate is added to this mixture, increasing from 10% in sample b to 90% in sample j. Sample /r is the result of photopolymerization of the diacrylate in the absence of thiol. Radical transfer from acrylate chains to thiols results in shorter acrylate chains, and thus in flexibility and heterogeneous free volume distribution. Data obtained at a scan rate 2° C min" . ...

Thiol radical RS is produced by radical I. RS initiates polymerization of methacrylate to give enethiol hardening, which shows a three-dimensional network structure (elastic). Thiol RSH also reacts with oxygen, as shown in Figure 1.5. Therefore, thiols protect from oxygen inhibition for polymerization. Multifunctional thiol is also effective for high sensitization of polymerization. 

This puts some doubt on the hypothesis that disulphide formation stems from dimerization of free thiol radicals as indicated in the simplified mechanism (Scheme 7) reported below. 

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