24
1 Melanin Chemistry
RD treatment [111], may also be important for the progression of vitiligo lesions by
inhibiting the regulatory T-cell functions [122].
Thus, these o-quinones have attracted attention as a selective cytotoxic drug. As
mentioned above, this cytotoxicity is being considered for applications to depigmentation therapy (by monobenzone) and anti-melanoma treatments (N-propionyl4-S-CAP, etc.). On the other hand, as in the case of RD-containing skin-whitening
agents, this cytotoxicity acts in an unintended manner, causing adverse effects. To
solve such melanin chemistry-related clinical problems, it is necessary to clarify the
relation between o-quinone reactivity and cytotoxicity. However, our mechanistic
understanding of o-quinone reactions is still far from complete due to the short lifetime of the participating molecules. Understanding melanin chemistry at the atomic
and the electronic scale is an important step for predicting o-quinone reactivity.
1.7 Summary of This Chapter and Scope of This Book
Melanin is a mixed pigment of eumelanin and pheomelanin. Eumelanin is formed
in the oxidative polymerization of DHI and DHICA, while pheomelanin is mainly
built from benzothiazine and benzothiazole.
Section 1.2 of this chapter introduced that the ratio of eumelanin/pheomelanin and
of DHI/DHICA are quantifiable and define the chemical composition of melanin.
In Sect. 1.3, the initial processes of melanogenesis were reviewed. Tyrosinasecatalyzed oxidation of tyrosine or dopa produces dopaquinone, which then converts
into DHI and DHICA via dopachrome, resulting in eumelanin production. This
spontaneous conversion of dopaquinone is triggered by intramolecular cyclization.
As mentioned in Sect. 1.5, in contrast, the binding of cysteine with dopaquinone
causes pheomelanin production. As implications of melanin chemistry to dermatology and cosmetic science, Sect. 1.6 reviewed melanocyto-specific cytotoxicity of
tyrosine/dopa analogs, which are oxidized by tyrosinase to cause melanogenesis-like
reactions by forming reactive o-quinones.
If these melanogenesis-like reactions are manipulable by molecular design, more
broadened applications of melanin chemistry to various fields are expected. Specifically, by making use of the photoelectronic properties, tissue compatibility, and
biodegradability, melanin chemistry may also be applied to electronics and tissue
engineering, as described in Sect. 1.1. In addition, in order to predict any adverse
effects of drugs administered to melanocyte-containing tissues, it is necessary to
understand the relationship between melanogenesis-like reaction and the cytotoxicity
as described in Sect. 1.6.
Melanogenesis includes a branched reaction in the course of reaction. For
example, dopaquinone is located at the branch point, and thus competitive processes,
namely cyclization and binding of thiols, respectively produce eumelanin and
pheomelanin. Furthermore, after dopaquinone cyclization, a eumelanogenic intermediate dopachrome undergoes spontaneous conversion to form the two possible
eumelanin monomers DHI and DHICA. At this second branch point, DHI is formed
1 Melanin Chemistry
RD treatment [111], may also be important for the progression of vitiligo lesions by
inhibiting the regulatory T-cell functions [122].
Thus, these o-quinones have attracted attention as a selective cytotoxic drug. As
mentioned above, this cytotoxicity is being considered for applications to depigmentation therapy (by monobenzone) and anti-melanoma treatments (N-propionyl4-S-CAP, etc.). On the other hand, as in the case of RD-containing skin-whitening
agents, this cytotoxicity acts in an unintended manner, causing adverse effects. To
solve such melanin chemistry-related clinical problems, it is necessary to clarify the
relation between o-quinone reactivity and cytotoxicity. However, our mechanistic
understanding of o-quinone reactions is still far from complete due to the short lifetime of the participating molecules. Understanding melanin chemistry at the atomic
and the electronic scale is an important step for predicting o-quinone reactivity.
1.7 Summary of This Chapter and Scope of This Book
Melanin is a mixed pigment of eumelanin and pheomelanin. Eumelanin is formed
in the oxidative polymerization of DHI and DHICA, while pheomelanin is mainly
built from benzothiazine and benzothiazole.
Section 1.2 of this chapter introduced that the ratio of eumelanin/pheomelanin and
of DHI/DHICA are quantifiable and define the chemical composition of melanin.
In Sect. 1.3, the initial processes of melanogenesis were reviewed. Tyrosinasecatalyzed oxidation of tyrosine or dopa produces dopaquinone, which then converts
into DHI and DHICA via dopachrome, resulting in eumelanin production. This
spontaneous conversion of dopaquinone is triggered by intramolecular cyclization.
As mentioned in Sect. 1.5, in contrast, the binding of cysteine with dopaquinone
causes pheomelanin production. As implications of melanin chemistry to dermatology and cosmetic science, Sect. 1.6 reviewed melanocyto-specific cytotoxicity of
tyrosine/dopa analogs, which are oxidized by tyrosinase to cause melanogenesis-like
reactions by forming reactive o-quinones.
If these melanogenesis-like reactions are manipulable by molecular design, more
broadened applications of melanin chemistry to various fields are expected. Specifically, by making use of the photoelectronic properties, tissue compatibility, and
biodegradability, melanin chemistry may also be applied to electronics and tissue
engineering, as described in Sect. 1.1. In addition, in order to predict any adverse
effects of drugs administered to melanocyte-containing tissues, it is necessary to
understand the relationship between melanogenesis-like reaction and the cytotoxicity
as described in Sect. 1.6.
Melanogenesis includes a branched reaction in the course of reaction. For
example, dopaquinone is located at the branch point, and thus competitive processes,
namely cyclization and binding of thiols, respectively produce eumelanin and
pheomelanin. Furthermore, after dopaquinone cyclization, a eumelanogenic intermediate dopachrome undergoes spontaneous conversion to form the two possible
eumelanin monomers DHI and DHICA. At this second branch point, DHI is formed