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Effect of pH on elementary steps of dopachrome conversion from first‐principles calculation
Author(s) -
Kishida Ryo,
Ushijima Yohei,
Saputro Adhitya G.,
Kasai Hideaki
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12256
Subject(s) - chemistry , quinone methide , decarboxylation , deprotonation , monomer , stereochemistry , photochemistry , biochemistry , organic chemistry , quinone , catalysis , ion , polymer
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 .