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

Ryo Kishida, Yohei Ushijima, Adhitya G. Saputro, Hideaki Kasai

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)734-743
Number of pages10
JournalPigment cell & melanoma research
Volume27
Issue number5
DOIs
Publication statusPublished - Sep 1 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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