Dopachrome conversion, in which dopachrome is converted into 5,6-dihydroxyindole (DHI) or 5,6-dihydroxyindole-2-carboxylic acid (DHICA) upstream of eumelanogenesis, is a key step in determining the DHI/DHICA monomer ratio in eumelanin, which affects the antioxidant activity. Although the ratio of DHI/DHICA formed and the conversion rate can be regulated depending on pH, the mechanism is still unclear. To clarify the mechanism, we carried out first-principles calculations. The results showed the kinetic preference of proton rearrangement to form quinone methide intermediate via β-deprotonation. We also identified possible pathways to DHI/DHICA from the quinone methide. The DHI formation can be achieved by spontaneous decarboxylation after proton rearrangement from carboxyl group to 6-oxygen. α-Deprotonation, which leads to DHICA formation, can also proceed with a significantly reduced activation barrier compared with that of the initial dopachrome. Considering the rate of the proton rearrangements in a given pH, we conclude that the conversion is suppressed at acidic pH.
Keywords: DHI; DHICA; dopachrome; eumelanin; first-principles calculation; pH effect.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.