Quinoid free radicals

Free radicals are ubiquitous. They are found in living plants and for practical purposes are essential to all life. They also exist in plant material that is dried. These types of free radicals are called persistent free radicals and are normally associated with free radicals present in the structural biomass of the plant (polyphenols, carbohydrates, and lignin). The tobacco precursors of free radicals found in the particulate phase of cigarette mainstream smoke (MSS) are also long-lived, persistent free radicals but arise from the thermolysis of the tobacco biomass to form numerous types of phenolic and quinoidal free radicals [Wooten et al. (27A120)]. Short-lived free radicals are also present in the vapor phase... 

In his investigations of the mechanism of action of the flavoproteins, Beinert 24) studied the spectral changes induced by enzjrmic or chemical reduction and oxidation of FMN and FAD. Evidence has been obtained for two intermediates, a semi-quinoid free radical, monomeric form, and a dimeric (possibly quinhydrone-hke) form of the free radical, which is formed from the monomer in a relatively slow reaction. The semi-quinones are formed rapidly enough to permit them to function kinetically as intermediates. A reaction scheme has been proposed 24). 

To understand the overall biological activity of quinoid compounds, it is necessary to study the chemical properties of these substances. Inasmuch as the cellular damage that is induced by quinones resembles that seen after radiolysis, the most prominent reactions involving quinones are probably DNA damage and generation of oxygen free radicals. 

This interpretation agreed with the chemical behavior of triphenylmethyl , with the free radical as the reactive species present in a low concentration and the dimer as a reservoir for it. However, most chemists at this time preferred to leave out the free radical and instead defend the notion of an unusually reactive dimer, such as for example the quinoid structure 1 or its symmetrical analogue 2 or even hexaphenylethane. 

In the light of the more complete study of ring-halogenated triphenylchloro-methanes in this paper, the free radical hypothesis was back - if it ever was excluded in the previous paper - in the final discussion of the constitution of triphenylmethyl , now with two tautomeric triphenylmethyl radical structures in equilibrium with each other and the Jacobson dimer 1 (Scheme 2). Note that the radical was symbolized by an open valence (a thick line is used here for clarity). The strong results obtained with 3 (Scheme 1) were explained by removal of the quinoid bromine atom from 4 giving a radical 6 which tautomerized to the triphenylmethyl analogue 7. By analogy with the... 

Metodiewa D, Jaiswal AK, Cenas N, Dickancaite E, Segura-Aguilar J. 1999. Quinone may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal products. Free Radic Biol Med 26 107-116. 

The electrophiles or electrophilic intermediates that are or are postulated to be responsible for the carcinogenic action of chemicals include (i) positively charged carbonium, nitrenium, oxonium and episulfonium ions, (ii) free radicals, (iii) polarized double bonds, (iv) aldehydes, (v) strained rings such as epoxide, aziridine, lactones and sultones, and (vi) quinone/ quinoid/quinoneimine structures. Based on their reactivity (Table I), electrophiles may be graded from "soft" to "hard" similar to the concept of "soft" and "hard" acids and bases (18). In general, soft electrophiles react preferentially with soft nucleophiles whereas hard electrophiles react preferentially with hard nucleophiles. Thus, since the nucleophilic sites in the purine and pyrimidine bases in DNA are moderately hard nucleophiles, moderately hard electrophiles tend to have the greatest likelihood of covalent binding to DNA. Soft electrophiles often deplete the cellular pool of noncritical soft nucleophiles (such as GSH) before they can react with DNA. 

Brown, R.F.C. Pyrolytic methods in organic chemistry, Academic Press, New York, Chapters 3-9 (1980). Brunmark, A. and E. Cadenas Redox and addition chemistry of quinoid compounds and its biological imphea-tions Free Radical Biol. Med. 7 (1989) 435 77. 

Note that the phenoxide radical has several resonance structures including those which contain the free radical inside the benzene ring. This radical may attack phenol to form a dimer which quickly tautomerizes to give 4,4 -di-hydroxybiphenyl, which in turn will repeat the previous sequence to form a more complex quinoid structure or it may react with the peroxide catalyst to form a two ringed quinone. Summarizing ... 

C.2 for further discussion of electron-mediated reductions) (Schwarzenbach, et al., 1990 Tratnyek and Macalady, 1989). Quinoid-type compounds are thought to be constituents of natural organic matter (Thurman, 1985 see Chapter l.B.3c). It has been hypothesized that some free radicals in humic substances are quinone-hydroquinone redox couples (Tollin et al., 1963 Steelink and Tollin, 1967). 

Two of the most commonly used substrates of ceruloplasmin are paraphenylene-diamine (PPD) and N, N-dimethyl-paraphenylenediamine (DPD). DPD, which has been used most extensively, is oxidized in a one-electron process to DPD+ which is intensely colored and allows ready observation of the course of the reaction. It has been well established that both substrates are initially oxidized to their respective radical cations. Broman et al. (88) studied the oxidation of PPD, observed free radical formation during catalysis, and identified this species as PPD+ by EPR techniques. Very convincing evidence was also presented that this free radical was neither bound to the enzyme nor acted as a substrate toward ceruloplasmin, but instead rapidly disproportionated to PPD and the quinoid form of PPD. 

Squadrito GL, Cueto R, Dellinger B, Pryor WA (2001) Quinoid redox cycling as a mechanism for sustained free radical generation by inhaled airborne particulate matter. Free Radic Biol Med 31 1132-1138... 

Sioutas C, Koutrakis P, Burton RM (1995) A technique to expose animals to concentrated fine ambient aerosols. Environ Health Perspect 103 172-177 Sioutas C, Delfino RJ, Singh M (2005) Exposure assessment for atmospheric ultrafine particles (UFPs) and implications in epidemiologic research. Environ Health Perspect 113 947-955 Southern Ontario Centre for Atmospheric Aerosol Research (SOCAAR) (2007) FacUities-Concentrated Ambient Particle Exposure Facility (CAPEF). http //www.socaar.utoronto.ca/ fac-inst/Facilities.htm. Accessed 21 September 2009 Squadrito GL, Cueto R, Dellinger B et al (2001) Quinoid redox cycling as a mechanism for sustained fiee radical generation by inhaled airborne particulate matter. Free Radic Biol Med 31 1132-1138... 

Diaryl Amines. The most active free-radical chain-breakers are diaryl amines. These generally discolor badly due to formation of quinoid structures, so they are not often used in plastics. In rubber, where the many C=C bonds create a great need for stabilization, and where carbon black generally masks any discoloration, diaryl amines are almost universally used. In plastics containmg carbon black, they may also be used very effectively. 

Theoretically, the condensation of mono- and diiodotyrosine could yield four different compounds 3,3 -diiodothyronine, 3,3, 5 -triiodothyronine, 3,5,3 -triio-dothyronine, and thyroxine (see Fig. 8-4). The exact mechanism of the formation of these various iodinated derivatives is not clear, but it has been suggested that they are formed by the condensation of two molecules of iodotyrosines with loss of a side chain. In this reaction, the iodinated tyrosine is converted by the loss of two atoms of hydrogen to the quinoid form, which acts as a free radical and condenses with other molecules of iodinated tyrosine to yield a diphenyl ring. During such a reaction, an oxygen bridge is formed, and one of the side chains of tyrosine is split to yield an a-amino acrylic acid. The a-amino acrylic acid is further metabolized to yield ammonia and pyruvic acid. 

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