Pulse radiolysis detection and computational analysis of quinones from 5,6-dihydroxyindole dimers: implication for eumelanin build up

Eumelanin structure and build up is still a challenge. Two models have been proposed to account for the unique properties of eumelanin: one put forward by Simon (Clancy and Simon, 2001) envisages a planar oligomer of 5,6-dihydroxyindole (DHI) /5,6-dihydroxyindole-2-carboxylic acid (DHICA) units which assembles through -stacking and side-on interactions, while the other (Cheng et al, 1994) depicts five to seven monomers of 5,6-indolequinone arranged in a plane, forming 3-4 layers stacked 3.4 Å apart. To probe either of these hypotheses, we underwent a systematic characterisation of oligomers of DHI and DHICA and their oxidation chemistry. Here we report the use of combined pulse radiolysis and quantum mechanical calculations to inquire into the nature of the species formed by oxidation of three dimers of DHI, namely 5,6,5’,6’-tetrahydroxy-2,2’-biindolyl, 5,6,5’,6’-tetrahydroxy-2,4’-biindolyl and 5,6,5’,6’-tetrahydroxy-2,7’-biindolyl. Pulse radiolytic oxidation of 2,4’- and 2,7’-biindolyls led to semiquinones absorbing around 450 nm, which decayed to give the corresponding quinones (500-550 nm). 2,2’-Biindolyl, on the other hand, furnished a semiquinone (max 480 nm) which disproportionated to give a relatively stable quinone ( max 580 nm). A quantum mechanical investigation of o-quinone, quinone imine and quinone methide structures of the dimers suggested that in the oxidised forms they exist mainly as 2-substituted extended quinomethane tautomers stabilised by intramolecular hydrogen bonds, reaching a planar conformation which is not favoured for the reduced forms. Overall, these results indicate that oxidation of oligomers to quinonoid species is critical to achieve planar assemblies which can interact by pi-stacking