Pulse radiolysis studies of ortho-quinone chemistry relevant to melanogenesis.

Abstract

The contributions of pulse radiolysis towards characterisation of unstable ortho-quinones relevant to melanogenesis are reviewed. The quinones discussed include dopaquinone, the precursor of both eumelanogenesis and phaeomelanogenesis, and 5-S-cysteinyldopaquinone, an early component of the phaeomelanogenic pathway. Redox exchange between dopaquinone and 5-S-cysteinyldopa is shown to be a determinant of the balance between eumelanogenesis and phaeomelanogenesis. Ortho-quinones resulting from the oxidation of tertiary N,N-dialkylcatecholamines cyclise to redox-inactive betaines which fail to autoactivate tyrosinase. This is consistent with the dopa detected during melanogenesis catalysed by tyrosinase being formed indirectly by a combination of dopaquinone intramolecular reductive addition to form leucodopachrome (cyclodopa), followed by redox exchange between remaining dopaquinone and leucodopachrome. Rapid tautomerism of the ortho-quinone of 4-cyanomethylcatechol to a redox-inactive quinomethane likewise inhibits tyrosinase autoactivation. The incorporation of trihydric phenol moieties in melanin is modelled by the reactions of several ortho-quinones with phloroglucinol, which itself is not directly oxidised by tyrosinase due to the meta-positioning of the hydroxyl groups. The importance of a susceptibility towards nucleophilic attack as well as a propensity to undergo redox-exchange, in the chemistry of melanogenic ortho-quinones, is emphasised.