5,6-Dihydroxyindole Tetramers with "Anomalous" Interunit Bonding Patterns by Oxidative Coupling of 5,5',6,6'-Tetrahydroxy-2,7'-biindolyl: Emerging Complexities on the Way toward an Improved Model of Eumelanin Buildup.

Chem. or enzymic oxidn. of 5,6-dihydroxyindole (I) leads to the rapid deposition of a black solid resembling eumelanin pigments by way of a complex oligomerization/polymn. process that proceeds in the early stages via dimers and trimers characterized by 2,4'- and 2,7'-couplings. Despite extensive efforts, the structures of the higher oligomers, which define the structural architecture and physicochem. properties of the eumelanin particles, have so far defied elucidation. Using a dimer-dimer coupling strategy that has recently allowed the first successful entry to a tetramer of I, the authors report now three addnl. tetramers obtained by oxidn. of 5,5',6,6'-tetrahydroxy-2,7'-biindolyl with the peroxidase/H2O2 system. On the basis of extensive 2D NMR and mass spectrometric anal., the products were identified as acetylated II (3%), III (4%), and IV (5%), in which the inner units are linked through unexpected 3,3'-, 4,4'-, and 2,3'-linkages. If verified in further studies, the newly uncovered coupling patterns would entail important consequences for current models of eumelanin structure based on one-dimensional structural chains with extended p-electron conjugation or p-stacked flat oligomer aggregates.