Synthetic Melanins

The subsequent conversion of these intermediates to eumelanins is still far from being well understood and represents a major focus for further work aimed at a definite understanding of the structure of both natural and synthetic melanins. 

This section includes a list of various artificial melanins classified by substrate (Table II), as well as a discussion of the four synthetic methods mentioned above. 

ADR Oxidation (NADH) and reduction [K3Fe(CN)6,2,6-dichlorophenolindophenol] studies 195 

BZQ-2M-3I Reversible two-electron reduction at a carbon paste electrode 197 

Kinetics of first step of melanization process to dopachrome 

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Krol, E.S. and Liebler, D.C., Photoprotective action of natural and synthetic melanins, Chem. Res. Toxicol, 11, 1434, 1998. 

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. 

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. 

We have also employed melanin from synthetic sources and Sepia officinalis. However, synthetic melanin has a structure distinctly different from naturally occurring melanins, and therefore it makes a poor model for hair melanin. Based on these results, melanin may play a role in some drug binding, especially for highly lipophilic drugs, but this role may be overshadowed by that played by the hair protein matrix. 

Natural melanins are generally differentiated by their origin, e.g., bovine eye, melanoma, sepia melanin. They usually occur in the form of granular particles, the melanosomes, and are secretory products of pigment-producing cells, the melanocytes. Synthetic melanins are named after the compound from which they were prepared via chemical or enzymatic oxidation (e.g., (/./-dopa, 5,6-dihydroxyindole, catechol melanin). 

Efficiency of radical production is threefold greater than from synthetic melanin produced by oxidation of 88... 

As far as the mechanism of polymerization of 5,6-dihydroxyindoles is concerned, kinetic experiments (I84J94) and pulse irradiation studies (190) suggest that coupling proceeds via oxygen-centered semiquinone radicals. If confirmed, such reactive intermediates may account for the complexity of the later stages of melanogenesis and the heterogeneity of natural and synthetic melanins. 

The relatively poor solubility of natural and synthetic eumelanins (Table IV) is a considerable obstacle in structural determination. The rate of particle sedimentation in aqueous suspensions of synthetic melanins is... 

The second approach to solubilization involves treatment of natural melanosomes and synthetic melanins with a dilute solution of hydrogen peroxide at pH 9-10 (303). The solubilized melanin precipitates under acidic conditions and is readily redissolved in basic media. There is only a slight increase in the carboxyl content, suggesting only limited degradation of the pigment. The fact that melanins can be solubilized in both polar and nonpolar media is a clear manifestation of the ability of the melanin structure to accommodate highly diverse demands on its solvation characteristics. 

The understanding of melanin structure has been attempted via analytical and biosynthetic approaches. The analytical one originally explored by Nicolaus (3,7,310) has led to the development of a number of useful methods for characterizing natural and synthetic melanins in terms of elemental composition, functional groups, and structural features of the pigment backbone. These methods helped in the elucidation of the partial polymeric structure of the eumelanin sepiomelanin (3) seen below. 

Pyrrolecarboxylic acids are the final products of oxidative degradation of eumelanins. The origin, reaction conditions, as well as the isolation and identification techniques used are the factors responsible for the different ratios of di-, tri-, and tetracarboxylic acids formed (7). Thus, untreated sepiomelanin and a number of synthetic melanins oxidized via KMNO4 showed the following trend in the relative ratios of pyrrolecarboxylic acids 2,3,5 2,3 = 2,3,4,5. The same samples after decarboxylation at 200°C followed the sequence 2,3,5 > 2,3 > 2,5 2,4 = 2,3,4,5. The decrease in 2,3,5 triacids and the increase in 2,3 diacids are attributed to the loss of carboxyl groups owing to the thermal treatment (7). Resistance to further oxidative degradation u der specific experimental conditions may substantially influence the ratio of the individual pyrrolecarboxylic acids formed (315). 

Experiments using a different approach gave somewhat different results. Working with melanin suspensions in 0.1 M hydrochloric acid, Strzelecka obtained an Eq value 1.4 eV and was able to reveal the presence of a band of states at the Fermi level (364). Despite the discrepancies, attributed to differences in the nature of the samples (melanins are very sensitive to degree of hydration and pH) the experiments confirm the consistency of the proposed model and provide useful data for further interpretation of the physical properties of melanins. Typical figures are a = 10 -10 fl" cm" (Ep - Ey) = 1 eV, and Eq = 1.4-3.4 eV for synthetic melanins from L-dopa and hydroquinone (365) and for natural melanins extracted from bovine eyes, hair, and banana peels (82). 

Solid-state NMR studies were performed on various biomolecules nucleosides [13] d,l-methionine [14] and selenomethionine [15], aminoacids and peptides [16], [17], [18], [19] natural and synthetic melanins [20], flavonoids [8], p-carotene [21], a- and P-D-glucose [22], lactose [23], lactulose [24], sugar derivatives of tocopherol [25] and numerous other sugar derivatives [26]. 

A recent study of sodium hydroxide degradation of both natural and synthetic melanins has revealed the formation of two different components one (more stable under the reaction conditions used) absorbing in the visible region, and a second absorbing in the UV region. It was postulated that the former is composed of stakes of planar monomer units and that the latter represents the core of the polymer, providing protective function against harmful UV radiation (70). 

Synthetic melanins are obtained by biomimetic oxidation reactions using known precursors. So far, four different methods for melanin synthesis have been reported, i.e. in vitro enzymatic, autooxidative, electrochemical, and photochemical methods. Of these, the first two have been generally used, for large scale preparations of the pigment polymers and have been reviewed elsewhere (70, 211). The latter two methods which are discussed here, have been used effectively to understand the mechanism of the melanization process in biological systems. 

Robson NC, Swan GA (1966) Studies on the Structure of Some Synthetic Melanins. In Della Prota G, Muhlbock O (eds.) Structure and Control of the Melanocytes, p. 155. Springer, Berlin Heidelberg New York... 

Zink, P. and D. Fengel Studies on the colouring matter of blue-stain fungi. Part 3. Spectroscopic studies on fungal and synthetic melanins. Holzforschung 44, 163 (1990). 

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... 

The formation of ROS was quantified using trapping ejqjeriments in which synthetic melanin films are treated with various metal salt solutions. After equilibration and extensive washing, the sanq)les were allowed to auto-oxidize under air in the presence of the radical trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Electron paramagnetic resonance characterization of the trapped ROS showed an distinctive increase in melanin s auto-oxidation upon metal-ion binding.(25) The increase in HO radical trapped by DMPO after treating the melanin with solutions of Zn(II) and Cu(II) salts correlated with the increase in quinone imine concentrations predicted. 

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