Oxidation Chemistry of 5,6-dihydroxyindole dimers : a pulse radiolytic investigation of (semi)quinone intermediates and isolation of new tetramers

Investigation of the oxidative polymerization of 5,6-dihydroxyindoles remains one of the most fruitful approaches toward definition of the structure of eumelanins. Previous studies by our group led to isolation of a collection of dimers and trimers which yielded the first insight into the stages of melanogenesis beyond dopachrome rearrangement. Attempts to isolate and characterize higher oligomeric intermediates were thwarted by the marked complexity of the product patterns. Recently, we reported an alternative approach to this issue involving biomimetic oxidation of 5,6-dihydroxyindole dimers, leading for the first time to novel tetramer species. For example, oxidation of the 4,4’dimer of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) yielded a mixture of isomeric tetramers linked through the 7-position and featuring chiroptical properties arising from atropoisomerism at the biphenyl linkages. Herein, we report the pulse radiolytic investigation of the oxidation of 2,4’ and 2,7’dimers of 5,6-dihydroxyindole (DHI). The results provided evidence for the formation of two different semiquinone species for each dimer, which decayed with second order kinetics to quinonoid product(s) exhibiting absorption maxima at 530 and 550 nm. The symmetric 2,2’dimer on the other hand furnished a single semiquinone disproportionating at a much slower rate to give a quinone with absorption maximum at 580 nm. Peroxidase/H2O2 oxidation of the 2,4’ and 2,7’ dimers of DHI gave tetramer products, the major of which were characterized by extensive 2D-NMR and mass spectrometry. The results disclosed unexpected differences in the mode of coupling of the dimers compared to DHI