Melanin radical

Very few radicals exist in tissues at rest . Two important exceptions are melanin radicals and tyrosine radicals. The former exist in low concentrations in samples of melanin, which is a high polymer made up of units which include potential semiquinone units. It is reasonable to expect some orf/io-semiquinone formation from such structures. The radicals can be thought of as occluded, being sterically protected by surrounding polymer. So far as we know, they have no special chemical significance. 

Kim BG, Kim S, Lee H, Choi JW (2014) Wisdom from the human eye a synthetic melanin radical scavenger for improved cycle life of Li-02 battery. Chem Mater 26 4757-4764... 

Heavily pigmented wools such as karakul require a more stringent approach, known as mordant bleaching, in which a metal salt is first appHed. The metal cations ate preferentially absorbed by the melanin pigment, where they subsequendy decompose hydrogen peroxide to produce highly aggressive hydroxyl free radicals, which then attack and bleach the melanin (114). 

Rozanowska, M. et al., Free radical scavenging properties of melanin interaction of eu- and pheo-melanin models with reducing and oxidising radicals. Free Rad. Biol. Med., 26, 518, 1999. 

Ranadive, N.S. and Menon, I.A. (1986). Role of reactive oxygen species and free radicals from melanins in photoin-duced cutaneous inflammation. Pathol. Immunopathol. Res. 5, 118-139. 

One possible mechanism responsible for cooperative action of antioxidants is reduction of a semi-oxidized carotenoid by another antioxidant. Carotenoid cation radicals can be reduced, and therefore recycled to the parent molecule, by a-tocopherol, ascorbate, and melanins (Edge et al., 2000b El-Agamey et al., 2004b) (Figure 15.5). Interestingly, lycopene can reduce radical cations of other carotenoids, such as astaxanthin, (3-carotene, lutein, and zeaxanthin (Edge et al., 1998). 

Edge, R, Land, EJ, Rozanowska, M, Sama, T, and Truscott, TG, 2000b. Carotenoid radical-melanin interactions. J Phys Chem B 104, 7193-7196. 

K. Akeo, S. Amaki, T. Suzuki, and T. Hiramitsu, Melanin granules prevent the cytotoxic effects of L-DOPA on retinal pigment epithelial cells in vitro by regulation of NO and superoxide radicals. Pigm. Cell. Res. 13, 80-88 (2000). 

Copper is part of several essential enzymes including tyrosinase (melanin production), dopamine beta-hydroxylase (catecholamine production), copper-zinc superoxide dismutase (free radical detoxification), and cytochrome oxidase and ceruloplasmin (iron conversion) (Aaseth and Norseth 1986). All terrestrial animals contain copper as a constituent of cytochrome c oxidase, monophenol oxidase, plasma monoamine oxidase, and copper protein complexes (Schroeder et al. 1966). Excess copper causes a variety of toxic effects, including altered permeability of cellular membranes. The primary target for free cupric ions in the cellular membranes are thiol groups that reduce cupric (Cu+2) to cuprous (Cu+1) upon simultaneous oxidation to disulfides in the membrane. Cuprous ions are reoxidized to Cu+2 in the presence of molecular oxygen molecular oxygen is thereby converted to the toxic superoxide radical O2, which induces lipoperoxidation (Aaseth and Norseth 1986). 

The resulting, synthetic melanin were black powder and absorbed light over the ultraviolet and visible regions (Tab. IV). They contained very stable free radical, being of interest to physiology. 

In a study of intermediate duration, dermal application of 0.5% p-cresol for 6 weeks produced permanent depigmentation of the skin and hair of mice (Shelley 1974). A caustic effect on the skin was noted in one strain of mouse, but not another. Neither o- nor m-cresol produced any color change in the mice. The author suggests that only p-cresol is active because it mimics the structure of tyrosine, the amino acid present in melanin, so that tyrosinase acts on it, liberating free radicals that damage melanocytes. NOAEL and LOAEL values were not derived from this study because the applied dose was not reported. 

Finally superoxide radicals can also be generated photochemically in chloroplasts in the presence of ascorbate or of paraquat. The formation was demonstrated by spin trapping on illumination of spinach chloroplasts in the presence of oxygen and paraquat Superoxide radicals are formed, moreover, in the near-ultraviolet photooxidation of tryptophan, as indicated by the increase of the HjO production in the presence of SOD and on irradiation in aerated solutions of protoporphyrin at 400 nm and of melanin with light of 320—600nmas shown by spintrapping. 

With tyrosinase, on the contrary, a two-electron oxidation occurs, as no EPR signal was detected in the catechol oxidation at pH 5.3 Melanins are polymerization products of tyrosine, whereby tyrosinase catalyses the first steps the formation of dopa (3,4-dihydroxyphenylalanine) and of dopaquinone, leading to an indolequi-none polymer The peroxidase mechanism for the conversion of tyrosine into dopa in melanogenesis was not substantiated In natural and synthetic melanins free radicals of a semiquinone type were detected by EPR 4-10 x 10 spins g of a hydrated suspension (the material was modified on drying and the number of free spins increased). The fairly symmetrical EPR signal had a g-value of 2.004 and a line-width of 4-10 G The melanins seem to be natural radical scavengers. 

Sealy, R. C. et al. Structure and reactivity of melanins Influence of free radicals and metal ions. 

Melanin, which is prepared by polymerization with a macromolecule-metal complex, is isolated as a black powder and shows strong absorption in the ultraviolet and visible regions. The free radical species is stable against heat, acid, and base, and the EPR shows a singlet signal at g = 2.00. These properties are also important in the physiological characteristics of melanin. 

Cells have substantial chemical defenses against the UV photoproducts produced in seawater and intracellular fluids. Many organisms have antioxidants (e.g., carotenoids, ascorbate, tocopherols, anthocyanins, and tridentatols) that quench photo-oxidative reactions.64-67 Cells also have enzymes (e.g., catalase and superoxide dismutase) that can counteract the oxidative nature of peroxides and other radicals.26 Some compounds, such as the UV-absorbing pigment melanin, can act as both optical filter and antioxidant.68 The MAA mycosporine-glycine (Figure 15.3) functions in a similar dual capacity.69 The role of UV-mediated reactions in seawater relative to biological effects is an important current area of study. 

Besides these enzyme substrates, a number of biological molecules are likely to give rise to fairly stable and hence observable free radicals. The more important of these are the quinonoid molecules, particularly vitamin Q quinone (ubiquinone), vitamin E quinone, vitamins K, Ks and vitamin E quinone, the flavins and flavoproteins and the important neurochemicals dopa, dopamine, and closely related phenolic and quinonoid molecules. In many of these cases, the generation of free radicals from these molecules should occur in vivo, but as yet only a few radicals such as the ascorbyl radical and the bacteriochlorophyll radical have been directly identified in intact systems. Free radicals from melanins (polymers from dopaquinone) have been demonstrated both in vivo and in vitro, but these radicals are so stable that it has not yet been possible to identify a biological role for the radicals per se. 

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