Knowledge Bank

Melanins are important natural pigments synthesized by small molecules via various obscure oxidation and polymerization reactions. Eumelanin, one of the melanins found in mammals, colors hair and eyes, provides photoprotection, binds to metal ions, and provides antioxidant properties. The atomistic structures present in eumelanin are unknown because all melanins are amorphous and recalcitrant to chemical analysis. Here, in a bottom-up approach to studying eumelanin, redox active, polymerization-inhibited molecular subunits of eumelanin are observed in the presence of heavy metal centers and differing pH. The molecules focused on include 5,6-dihydroxyindole (DHI) and its oxidized form indole-5,6,-quinone (IQ). Although these molecules were first identified in the 1920s as probable eumelanin subunits, their properties are poorly characterized due to the tendency of DHI and IQ to rapidly polymerize. This study utilizes derivatives of these compounds that have bulky ‘blocking’ groups installed at key carbons, which prevent carbon- carbon bond forming reactions but allow redox changes to take place. The first steady-state spectrum of the semiquinone radical (SQ) species is presented via stabilization with Zn(II) ions. EPR measurements show that the addition of Zn(II) ions to a solution of DHI-Me and IQ-Me increases the population of radicals dramatically. These results show the ability of monomeric SQ to bind to heavy metals, while elucidating the contribution of SQ to the broadband absorption of melanin. Additionally, the first high precision measurement of the pKa of IQ is reported, utilizing global analysis. This value may allow for future speciation of substructures in melanin with an understanding of how IQ responds to changes in acidity. Results from this study further our understanding of melanin towards usage in complicated chemical environments in medical and renewable energy biotechnology.