“Fifty Shades” of Black and Red or How Carboxyl Groups Fine Tune Eumelanin and Pheomelanin Properties

Abstract

Recent advances in the chemistry of melanins have begun to disclose a number of important structure-property-function relationships of crucial relevance to the biological role of human pigments, including skin (photo) protection and UV-susceptibility. Even slight variations in the monomer composition of black eumelanins and red pheomelanins have been shown to determine significant differences in light absorption, antioxidant, paramagnetic and redox behavior, particle morphology, surface properties, metal chelation and resistance to photo-oxidative wear-and-tear. These variations are primarily governed by the extent of decarboxylation at critical branching points of the eumelanin and pheomelanin pathways, namely the rearrangement of dopachrome to 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and the rearrangement of 5-S-cysteinyldopa o-quinoneimine to 1,4-benzothiazine (BTZ) and its 3-carboxylic acid (BTZCA). In eumelanins, the DHICA-to-DHI ratio markedly affects the overall antioxidant and paramagnetic properties of the resulting pigments. In particular, a higher content in DHICA decreases visible light absorption and paramagnetic response relative to DHI-based melanins, but markedly enhances antioxidant properties. In pheomelanins, likewise, BTZCA-related units, prevalently formed in the presence of zinc ions, appear to confer pronounced visible and ultraviolet A (UVA) absorption features, accounting for light-dependent reactive oxygen species (ROS) production, whereas non-carboxylated benzothiazine intermediates seem to be more effective in inducing ROS production by redox cycling mechanisms in the dark. The possible biological and functional significance of carboxyl retention in the eumelanin and pheomelanin pathways is discussed.

Critical Analysis of the Melanogenic Pathway in Insects and Higher Animals

“…This constraint dictates the sole production of DHICA melanin and not DHI melanin. However, all three different eumelanins, viz., DHI melanin, DHICA-DHI mixed melanin and DHICA melanin, are formed in mammalian systems [3,5,42,43]. For this to occur, obviously DHI has to be synthesized some how in comparable quantities to that of DHICA or even more.…”

“…Mammalian systems produce significant amounts of pheomelanin [42,43]. In contrast, the reports on the presence of pheomelanin in invertebrate animals and especially insects are very few [54].…”

Dark- or Light-Colored Melanins: Generating Pigments Using Fe2+ and H2O2

“…Although for many reaction mixtures no visible precipitations were observed and the aliquots of the reaction mixtures could be analyzed using SEC, we can not exclude the possibility that the pigment materials generated through the oxidation reactions may exist as aggregates of finely-dispersed small molecules as is discussed for MN pigments. [23][24][25] Fig.4, panel C, correlates the extent of the reactivity of the compound and the intensity of the color of the reaction mixture as evaluated through absorbance readings at 400nm. For all compounds, with the exception of (8), the absorbance increased with declining % of compound remaining up to the point when about 0% of the compound remained; typically when 0.075% v/v H 2 O 2 was present.…”

The modulation of melanin‐like materials: methods, characterization and applications

“…Recent studies found that a higher content of DHICA decreases visible light absorption and paramagnetic response relative to DHI‐based melanins, but enhances antioxidant properties. The presence of carboxyl groups shows a significant effect in the biological functions of eumelanins . Therefore, polydopamine and synthetic melanin may have more similarity with DHI‐based natural melanins.…”

“…There are many important reviews and key articles which introduce the research progress of polydopamine in different fields . In this paper, we focus on the modulation of synthetic melanin and polydopamine in chemical structures and aggregated nanostructures.…”