The Eumelanin carboxyl conundrum: unexpected impact of esterification on 5,6-dihydroxyindole-2-carboxlic acid antioxidant activity and oxidative polymerization

Distal to tyrosinase activity, eumelanin synthesis is governed by the rearrangement of dopachrome which may proceed with or without decarboxylation giving 5,6-dihydroxyindole (DHI) and/or 5,6-dihydroxyindole-2-carboxylic acid (DHICA), that exhibit different chemical and biological properties. In melanocytes the reaction occurs under strict enzymatic assistance directing the course of melanogenesis toward DHICA and preventing the spontaneous decarboxylation to DHI. To inquire into the role of the carboxyl group as determinant of the chemical properties of the 5,6-dihydroxyindole system, DHICA and its methyl ester were compared for both their antioxidant activity and their conversion to eumelanin chromophores via oxidative polymerization. The results revealed that DHICA ester oligomers are stronger antioxidant compared to the free acid ones. Moreover, whereas the spectrophotometric course of DHICA oxidation proceeds via a purple chromophoric phase followed by band broadening to give a dark brown eumelanin, DHICA ester is converted to light brown species devoid of the typical euemelanin properties. These results suggest that the carboxyl group plays a more complex role than simply blocking the 2-position of the indole ring. The actual biological significance of these observations and their possible exploitation for dermocosmetic applications are currently under assessment in our laboratory.