Chapter 2
Dopachrome Conversion
Abstract The color and redox properties of eumelanins are affected by the presence of the carboxyl groups in their indollic structural unit. The key reaction determining the amount of carboxyl groups in eumelanin is dopachrome conversion.
In this conversion, 5,6-dihydroxylindole (DHI) is spontaneously formed through
the elimination of the carboxyl group, namely decarboxylation, whereas the nondecarboxylated product 5,6-dihydroxylindole-2-carboxylic acid (DHICA) is also
formed in the presence of several factors such as dopachrome tautomerase (DCT) and
Cu(II) ion as well as strongly alkaline pH. In this chapter, we introduce computational
studies of dopachrome conversion with the emphasis on the branching into DHI and
DHICA formation. As a result, important factors affecting the selective formation
of DHI and DHICA were identified. These reaction modes are switched based on
the protonation/deprotonation of the quinonoid group of dopachrome. The catalytic
effects of basic pH and Cu(II), experimentally observed, can be explained based on
two aspects: (i) promotion of the rate-determining step, namely β-deprotonation
and (ii) protection of quinonoid group from protonation. Our approach clarifies
dopachrome conversion from atomic nuclei and electrons world.
Keywords Dopachrome · 5,6-dihydroxyindole (DHI) ·
5,6-dihydroxyindole-2-carboxylic acid (DHICA) · Deprotonation · Cu(II)
coordination · Density functional theory
2.1 Introduction
2.1.1 Background on Dopachrome Studies
Dopachrome conversion produces DHI and DHICA, which are the monomers of
eumelanin, and thus directly determines the properties of the eumelanin produced
(Fig. 2.1). It has been pointed out that eumelanin may not only protect the skin
and the hair from UV radiation but also play an important role in the scavenging
of intracellular ROS [1–3]. This antioxidant effect is likely to be derived from the
DHICA unit contained in eumelanin. Furthermore, DHICA itself or its methoxy
derivatives may also have physiologically important effects, including antioxidant
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021
R. Kishida et al., Melanin Chemistry Explored by Quantum Mechanics,
https://doi.org/10.1007/978-981-16-1315-9_2
33
Dopachrome Conversion
Abstract The color and redox properties of eumelanins are affected by the presence of the carboxyl groups in their indollic structural unit. The key reaction determining the amount of carboxyl groups in eumelanin is dopachrome conversion.
In this conversion, 5,6-dihydroxylindole (DHI) is spontaneously formed through
the elimination of the carboxyl group, namely decarboxylation, whereas the nondecarboxylated product 5,6-dihydroxylindole-2-carboxylic acid (DHICA) is also
formed in the presence of several factors such as dopachrome tautomerase (DCT) and
Cu(II) ion as well as strongly alkaline pH. In this chapter, we introduce computational
studies of dopachrome conversion with the emphasis on the branching into DHI and
DHICA formation. As a result, important factors affecting the selective formation
of DHI and DHICA were identified. These reaction modes are switched based on
the protonation/deprotonation of the quinonoid group of dopachrome. The catalytic
effects of basic pH and Cu(II), experimentally observed, can be explained based on
two aspects: (i) promotion of the rate-determining step, namely β-deprotonation
and (ii) protection of quinonoid group from protonation. Our approach clarifies
dopachrome conversion from atomic nuclei and electrons world.
Keywords Dopachrome · 5,6-dihydroxyindole (DHI) ·
5,6-dihydroxyindole-2-carboxylic acid (DHICA) · Deprotonation · Cu(II)
coordination · Density functional theory
2.1 Introduction
2.1.1 Background on Dopachrome Studies
Dopachrome conversion produces DHI and DHICA, which are the monomers of
eumelanin, and thus directly determines the properties of the eumelanin produced
(Fig. 2.1). It has been pointed out that eumelanin may not only protect the skin
and the hair from UV radiation but also play an important role in the scavenging
of intracellular ROS [1–3]. This antioxidant effect is likely to be derived from the
DHICA unit contained in eumelanin. Furthermore, DHICA itself or its methoxy
derivatives may also have physiologically important effects, including antioxidant
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021
R. Kishida et al., Melanin Chemistry Explored by Quantum Mechanics,
https://doi.org/10.1007/978-981-16-1315-9_2
33