Eumelanin buildup on the nanoscale: aggregate growth/assembly and visible absorption development in biomimetic 5,6-dihydroxyindole polymerization.

Establishing structure-property relationships in the black insoluble eumelanins, the key determinants of human pigmentation and skin photoprotective system, is a considerable conceptual and experimental challenge in the current drive for elucidation of the biological roles of these biopolymers and their application as advanced materials for organoelectronics. Herein, we report a new breakthrough toward this goal by the first detailed investigation on the nanoscale level of the oxidative polymerization of 5,6-dihydroxyindole (DHI), a model process of eumelanin synthesis. On the basis of a combined use of spectrophotometry, dynamic light scattering (DLS), and small-angle neutron scattering (SANS) investigations, it was possible to unveil the dynamics of the aggregation process before precipitation, the key relationships with visible light absorption and the shape of fundamental aggregates.

Cyclic structural motifs in 5,6-dihydroxyindole polymerization uncovered: biomimetic modular buildup of a unique five-membered macrocycle.

An unprecedented 5,6-dihydroxyindole macrocycle (4) featuring a rigid twisted backbone was obtained by biomimetic oxidative cross-coupling of the 2,2'-biindole 2 and triindole 3. A putative reaction intermediate, 2-quinone, was detected and characterized by pulse radiolysis and DFT calculations. Discovery of 4 indirectly supports for the first time theoretically predicted cyclic structural motifs as potential eumelanin building blocks.

5,6-Dihydroxyindole oxidation in phosphate buffer/polyvinyl alcohol: a new model system for studies of visible chromophore development in synthetic eumelanin polymers.

The determinants of the broadband absorption spectrum of eumelanins are still largely unknown. Herein we report a novel approach to investigate eumelanin chromophore which is based on the biomimetic oxidation of the key monomer precursor, 5,6-dihydroxyindole (DHI, 1), with peroxidase/hydrogen peroxide in phosphate buffer, pH 7, containing 1-5% polyvinylalcohol (PVA, 27 000 Da). This approach relies on the discovery that as low as 1% PVA can prevent precipitation of the growing melanin polymer thus allowing investigation of the chromophoric phases accompanying oxidation of DHI without confounding scattering effects.

Chemistry of nitrated lipids: remarkable instability of 9-nitrolinoleic acid in neutral aqueous medium and a novel nitronitrate ester product by concurrent autoxidation/nitric oxide-release pathways.

Despite the mounting interest in nitrolinoleic acids and related nitrated polyunsaturated fatty acids as a novel class of bioactive signaling lipids, their chemistry and metabolic fate have remained poorly elucidated. Herein, we report an expedient nitroselenenylation/oxidation route to 9-nitrolinoleic acid (1) and 10-nitrolinoleic acid (2), which enabled comparative product studies under physiologically relevant conditions. Under biomimetic conditions, 1 decayed at an unusually fast rate to give the hydroxy-, keto-, and nitronitrate ester derivatives 3, 4, and 5 as main products, identified by ESI-MS and 2D NMR spectroscopy, including (1)H, (15)N HMBC experiments on the (15)N-labeled derivatives.

Structural effects on the electronic absorption properties of 5,6-dihydroxyindole oligomers: the potential of an integrated experimental and DFT approach to model eumelanin optical properties.

Elucidation of the relationships between structural features and UV-visible absorption properties of 5,6-dihydroxyindole oligomers is an essential step towards an understanding of the unique optical properties of eumelanins. Herein, we report the first combined experimental and density functional theory (DFT) investigation of the 5,6-dihydroxyindole oligomers so far isolated. 2,2'-Biindolyl 2 and the 2,4'-biindolyl 3 absorb at longer wavelengths relative to 2,7'-biindolyl 4 and their spectra were well predicted by DFT analysis.

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.

Chemical or enzymatic oxidation of 5,6-dihydroxyindole (1) leads to the rapid deposition of a black solid resembling eumelanin pigments by way of a complex oligomerization/polymerization process that proceeds in the early stages via dimers 2-3 and trimers 5-6 characterized by 2,4'- and 2,7'-couplings. Despite extensive efforts, the structures of the higher oligomers, which define the structural architecture and physicochemical 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 1, we report now three additional tetramers obtained by oxidation of 5,5',6,6'-tetrahydroxy-2,7'-biindolyl (3) with the peroxidase/H2O2 system.