Dioxide Radical

Oxidation of biphenyl-2-sulfonamide with persulfate gives a sulfonamidyl radical which cyclizes intramolecularly to yield, after further oxidation. 

A formal hydration of 241 at N would yield V-hydroxy heterocycles. While these species are not well characterized, their radical oxidation products the nitroxyls (246) are well known vide infra). It should be noted that these radicals, like 242-244, are in the third level of oxidation relative to the parent heterocycles. 

A formal hydration of 241 at X, only possible for X = S or Se, yields the corresponding sulfoxide (e.g., 247) or selenoxide of the heterocycle. No radicals have been substantiated, in the writer s view, which arise by further oxidation of heterocycles with oxidized group VI heteroatoms. 

The analysis of the ESR spectrum of 252 was correctly given early by Buchachenko the hyperfine splittings given in 252 are from the work of Aurich and co-workers who also determined the hyperfine splitting due to O in a labeled sample. This determination allows experimental confirmation of calculations on the distribution of spin in the nitroxyl radical function and has allowed the formulation of McLachlan MO parameters of general applicability in this type of radical. 

Unlike their phenothiazine counterparts, phenoxazinyl (253) and phen-oxazine 10-oxyl (254) were not confused. They were properly distinguished. 

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Subsequent studies (63,64) suggested that the nature of the chemical activation process was a one-electron oxidation of the fluorescer by (27) followed by decomposition of the dioxetanedione radical anion to a carbon dioxide radical anion. Back electron transfer to the radical cation of the fluorescer produced the excited state which emitted the luminescence characteristic of the fluorescent state of the emitter. The chemical activation mechanism was patterned after the CIEEL mechanism proposed for dioxetanones and dioxetanes discussed earher (65). Additional support for the CIEEL mechanism, was furnished by demonstration (66) that a linear correlation existed between the singlet excitation energy of the fluorescer and the chemiluminescence intensity which had been shown earher with dimethyl dioxetanone (67). 

Selective chlorination of the 3-position of thietane 1,1-dioxide may be a consequence of hydrogen atom abstraction by a chlorine atom. Such reactions of chlorine atoms are believed to be influenced by polar effects, preferential hydrogen abstraction occurring remotely from an electron withdrawing group. The free radical chain reaction may be propagated by attack of the 3-thietanyl 1,1-dioxide radical on molecular chlorine. 

Another way to prepare fluorinated sulfides is the photochemical alkylation of sulfides or disulfides by perfluoroalkyl iodides [69, 70, 71] (equations 62-64). Reaction of trifluoromethyl bromide with alkyl or aryl disulfides in the presence of a sulfur dioxide radical anion precursor, such as sodium hydroxymethanesulfi-nate, affords trifluoromethyl sulfides [72] (equation 65). 

Fluorinated sulflnates are prepared from sodium dithionite and liquid per-fluoroalkyl halides [74] (equation 67). For the transformation of the gaseous and poorly reactive trifluoromethyl bromide, it is necessary to use moderate pressure [75] (equation 68) These reactions are interpreted by a SET between the intermediate sulfur dioxide radical anion and the halide The sodium trifluorometh-anesulfinate thus obtained is an intermediate for a chemical synthesis of triflic acid. 

Radical pertluoroalky lation of anilines occurs in the presence of a sufur dioxide radical anion precursor, such as Zn-S02 or sodium dithionite [154, 755], or of a nickel complex [756] (equation 134)... 

Perfluoroalkylatwn ofpyridines by perfluoroalkyl bromides or iodides occurs m the presence of sulfur dioxide radical anion precursors, such as sodium hydroxy-methanesulfinate [755, 757, 158] (equation 135)... 

The formation of aryl radicals from benzenediazonium ions, initiated by electron transfer from a nitrite ion, has already been discussed in Section 8.6. It is an excellent example of a dediazoniation assisted by a donor species that is capable of forming a relatively stable species on release of an electron, in this case a nitrogen dioxide radical NO2 (Opgenorth and Rtichardt, 1974). 

Between sulfur dioxide radical anions, dithionite, and sulfoxylate/sulfite there exists a pH-dependent equilibrium465 (equation 86). Therefore, dithionite has been used as a source of sulfoxylate in order to prepare sulfinate and hence sulfones. Alkylation with triethyl oxonium fluoroborate leads to ethyl ethanesulfinate, alkyl iodides lead to symmetrical sulfones466 (equation 87). 

The ESR spectrum of the thioxanthene S, S-dioxide radical anion itself shows that the two possible conformers coexist, since the two methylene protons are not equivalent. In the case of the 9-monoalkyl derivatives, the large coupling constant observed for the 9-proton leads to the conclusion that the 9-substituent is in the boat equatorial position as in II1 F Thus the radical anions and the neutral molecule display different conformations. The protons in the 9-position of the radical anions of cis-9-methylthioxanthene S-oxides (2, n — 1, R1 = H, R2 = CH3) have an appreciable coupling constant10 which suggests that these radical anions have the substituent in the pseudo-axial position. Furthermore, in the radical anions the S—O bond is pseudo-axial. These situations are exactly the opposite of that observed for the neutral compound. 

Yonezawa and collaborators (99) have reported unrestricted open-shell SCF calculations where the one-center exchange integrals were taken into account their treatment concerned allyl, vinyl, and nitrogen dioxide radicals. The one-center exchange integrals also are involved in the INDO method (85). Here, the following relationship for hyperfine splitting constants holds ... 

The authors propose that an initial abstraction of a hydrogen atom produces a complex containing bound carbon dioxide radical-anion. This complex could break down in two ways... 

The electrophilic character of sulfur dioxide does not only enable addition to reactive nucleophiles, but also to electrons forming sulfur dioxide radical anions which possess the requirements of a captodative" stabilization (equation 83). This electron transfer occurs electrochemically or chemically under Leuckart-Wallach conditions (formic acid/tertiary amine - , by reduction of sulfur dioxide with l-benzyl-1,4-dihydronicotinamide or with Rongalite The radical anion behaves as an efficient nucleophile and affords the generation of sulfones with alkyl halides " and Michael-acceptor olefins (equations 84 and 85). 

Bohm, F., Tinkler, J.H., and Truscott, T.G. 1995. Carotenoids protect against cell membrane damage by the nitrogen dioxide radical. Nat. Med. 1 98-99. 

It has been proposed [91] that nitric dioxide radical formation during the oxidation of nitrite by HRP or lactoperoxidase (LPO) can contribute to tyrosine nitration and be involved in cell and tissue injuries. This proposal was supported in the later work [92] where it has been shown that N02 formed in peroxide-catalyzed reactions is able to enter cells and induce tyrosyl nitration. Reszka et al. [93] demonstrated that N02 mediated the oxidation of biological electron donors and antioxidants (NADH, NADPH, cysteine, glutathione, ascorbate, and Trolox C) catalyzed by lactoperoxidase in the presence of nitrite. 

Probably, the most convincing proof of free radical mechanism of peroxynitrite reactions is the formation of dityrosine [117,118]. It has been suggested [118] that the nitric dioxide radical is responsible for the formation of both 3-nitrotyrosine and dityrosine (Figure 21.1), however, hydroxyl radicals (which were identified in this system by ESR spectroscopy [119]) may also participate in this process. Pfeiffer et al. [118] proposed that dityrosine is predominantly formed at low fluxes of superoxide and nitric oxide, which corresponds to in vivo conditions, however, this observation was not confirmed by Sawa et al. [117],... 

The reaction of peroxynitrite with the biologically ubiquitous C02 is of special interest due to the presence of both compounds in living organisms therefore, we may be confident that this process takes place under in vivo conditions. After the discovery of this reaction in 1995 by Lymar [136], the interaction of peroxynitrite with carbon dioxide and the reactions of the formed adduct nitrosoperoxocarboxylate ONOOCOO has been thoroughly studied. In 1996, Lymar et al. [137] have shown that this adduct is more reactive than peroxynitrite in the reaction with tyrosine, forming similar to peroxynitrite dityrosine and 3-nitrotyrosine. Experimental data were in quantitative agreement with free radical-mediated mechanism yielding tyrosyl and nitric dioxide radicals as intermediates and were inconsistent with electrophilic mechanism. The lifetime of ONOOCOO was estimated as <3 ms, and the rate constant of Reaction (42) k42 = 2 x 103 1 mol 1 s 1. 

Microsomes are capable of oxidizing not only organic substrates but also inorganic ones. An interesting example is the metabolism of bisulfite (aqueous sulfur dioxide) in microsomes. Although mitochondrial sulfite oxidase is responsible for the in vivo oxidation of bisulfite by a two-electron mechanism, cytochrome P-450 is also able to reduce bisulfite to the sulfur dioxide radical anion [56] ... 

An attempt to combine electrochemical and micellar-catalytic methods is interesting from the point of view of the mechanism of anode nitration of 1,4-dimethoxybenzene with sodinm nitrite (Laurent et al. 1984). The reaction was performed in a mixture of water in the presence of 2% surface-active compounds of cationic, anionic, or neutral nature. It was established that 1,4-dimethoxy-2-nitrobenzene (the product) was formed only in the region of potentials corresponding to simultaneous electrooxidation of the substrate to the cation-radical and the nitrite ion to the nitrogen dioxide radical (1.5 V versus saturated calomel electrode). At potentials of oxidation of the sole nitrite ion (0.8 V), no nitration was observed. Consequently, radical substitution in the neutral substrate does not take place. Two feasible mechanisms remain for addition to the cation-radical form, as follows ... 

For the anode process at comparable conditions, the yield of l,2-dimethoxy-2-nitrobenzene depends distinctly on the electrical natnre of a micelle. Namely, the yields are equal to 30, 40, and 70% for the positively, negatively, and nentrally charged micelles, respectively. The observed micellar effect corroborates the mechanism that inclndes 1,4-dimethoxybenzene cation-radical and nitrogen dioxide radical as reacting species. 

The stmcture of the drug is unusual in possessing the thioether linkage antimicrobial activity depends on this feature as oxidation to the sulphone or the dioxide radically reduces activity. Increase in size of the alkyl radical also diminishes activity, trichomonacidal activity being demonstrable only in the methyl ether. 

Scheme 4 Proposed pathways for the reaction of nitrogen dioxide radical (NOj) with the neutral guanine radical.

Janzen EG, Towner RA, Brauer M. 1988. Factors influencing the formation of the carbon dioxide radical anion (CO2-) spin adduct of PBN in the rat liver metabolism of halocarbons. Free Radic Res Common 4 35-369. 

Peroxynitrous acid is a powerful oxidizing agent with estimated one- and two-electron reduction potentials of ° (ONOOH, H+/"N02, HjO) = 1.6-1.7 V and ° (ONOOH, H /N02 , H2O) = 1.3-1.4 V, respectively . In addition, it was reported that, upon protonation, ONOO can undergo decomposition via homolytic 0—0 cleavage to generate nitrogen dioxide radical ("NO2) and hydroxyl radical ( OH) in approximately 30% yields... 

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