Chapter 3
Dopaquinone Conversion and Related
Reactions
Abstract The biosynthetic pathway of melanin is branched into pheomelanogenesis and eumelanogenesis at the stage of dopaquinone conversion. In the presence
of intracellular thiols such as cysteine, dopaquinone binds to the sulfhydryl group
of thiols, whereas under lower concentration of thiols dopaquinone spontaneously
undergoes intramolecular cyclization through the alanyl side chain. The binding
of cysteine produces cysteinyldopa necessary for pheomelanogenesis, whereas the
cyclized product, cyclodopa further transforms into eumelanin. In this chapter, we
introduce computational studies for cyclization and thiol binding for dopaquinone
and structurally similar o-quinones with the emphasis on the competitive behavior
between the two reactions. As a result, remarkable charge redistributions were
observed during cyclization and thiol binding. From this point of view, the HOMO
and LUMO levels of o-quinone are pointed out as important factors affecting the
reactivity and the competition between the two reactions. Furthermore, a mechanistic issue of thiol binding is also discussed based on the atomic-scale simulation
results, which showed the presence of unusual reaction intermediate. Our approach
clarifies branched reactions of dopaquinone and resembling o-quinones from atomic
nuclei and electrons world.
Keywords Dopaquinone · o-quinone · Rhododendrolquinone · Cyclization · Thiol
binding · Density functional theory
3.1 Introduction
3.1.1 Background—Competition Between Cyclization
and Thiol Binding
In melanogenesis, the competitive reactions of dopaquinone controls the composition
of the generated melanin. Known possible reactions of dopaquinone are cyclization
and thiol binding (Fig. 3.1). The former results in eumelanogenesis while the latter
corresponds to the initiation of pheomelanogenesis.
Dopaquinone includes two adjacent carbonyl groups in the benzene ring. Hence,
this molecule is classified as o-quinone. In general, o-quinones are highly reactive
© 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_3
51
Dopaquinone Conversion and Related
Reactions
Abstract The biosynthetic pathway of melanin is branched into pheomelanogenesis and eumelanogenesis at the stage of dopaquinone conversion. In the presence
of intracellular thiols such as cysteine, dopaquinone binds to the sulfhydryl group
of thiols, whereas under lower concentration of thiols dopaquinone spontaneously
undergoes intramolecular cyclization through the alanyl side chain. The binding
of cysteine produces cysteinyldopa necessary for pheomelanogenesis, whereas the
cyclized product, cyclodopa further transforms into eumelanin. In this chapter, we
introduce computational studies for cyclization and thiol binding for dopaquinone
and structurally similar o-quinones with the emphasis on the competitive behavior
between the two reactions. As a result, remarkable charge redistributions were
observed during cyclization and thiol binding. From this point of view, the HOMO
and LUMO levels of o-quinone are pointed out as important factors affecting the
reactivity and the competition between the two reactions. Furthermore, a mechanistic issue of thiol binding is also discussed based on the atomic-scale simulation
results, which showed the presence of unusual reaction intermediate. Our approach
clarifies branched reactions of dopaquinone and resembling o-quinones from atomic
nuclei and electrons world.
Keywords Dopaquinone · o-quinone · Rhododendrolquinone · Cyclization · Thiol
binding · Density functional theory
3.1 Introduction
3.1.1 Background—Competition Between Cyclization
and Thiol Binding
In melanogenesis, the competitive reactions of dopaquinone controls the composition
of the generated melanin. Known possible reactions of dopaquinone are cyclization
and thiol binding (Fig. 3.1). The former results in eumelanogenesis while the latter
corresponds to the initiation of pheomelanogenesis.
Dopaquinone includes two adjacent carbonyl groups in the benzene ring. Hence,
this molecule is classified as o-quinone. In general, o-quinones are highly reactive
© 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_3
51