The role of carboxyl groups in eumelanin and pheomelanin properties

Recent advances in the chemistry of melanins have disclosed the importance of the monomer composition in determining significant differences in the pigment properties of crucial relevance to their biological role, including skin (photo)protection and UV-susceptibility. In this scenario, a key role seems to be played by carboxyl groups. Depending on the extent of decarboxylation during the rearrangement of dopachrome different contents of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) can be incorporated into eumelanin pigments. Rearrangement of 5-S-cysteinyldopa o-quinoneimine likewise can lead to 1,4-benzothiazine (BTZ)or its 3-carboxylic acid (BTZCA) derivative. The DHICA-to-DHI ratio markedly affects the antioxidant and chromophoric properties of eumelanins: in particular, high amounts of DHICA-derived units decrease visible light absorption relative to DHI-based melanins, but markedly enhance antioxidant properties. In the same way carboxylated benzothiazines can confer pronounced visible and UVA absorption features to pheomelanins, accounting for light-dependent reactive oxygen species (ROS) production, whereas BTZ-related units seem to be more effective in inducing ROS production by redox cycling mechanisms in the dark. The possible biological consequences of carboxyl group retention in the eumelanin and pheomelanin pathways will be discussed.