Effect of pH on elementary steps of dopachrome conversion from first‐principles calculation

Summary 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 p H , 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 p H , we conclude that the conversion is suppressed at acidic p H .