title: Effect of pH on elementary steps of dopachrome conversion from first-principles calculation.
abstract: 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.
authors.affiliation: Department of Applied Physics, Osaka University, Suita, Osaka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kishida
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ushijima
authors.forename: Adhitya G
authors.initials: AG
authors.lastname: Saputro
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kasai
mesh_terms: D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D045563:Indolequinones / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D010858:Pigmentation; D011522:Protons; D012984:Software; D012997:Solvents / Q000737:chemistry
chemical_list: D045563:Indolequinones; D007211:Indoles; D011522:Protons; D012997:Solvents; C068040:quinone methide; C001123:dopachrome; C030692:5,6-dihydroxy-2-indolylcarboxylic acid; D006859:Hydrogen; D019746:Intramolecular Oxidoreductases; C033871:5,6-dihydroxyindole
keywords: DHI; DHICA; dopachrome; eumelanin; first-principles calculation; pH effect