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. On the basis of extensive 2D NMR and mass spectrometric analysis, the products were identified as 5,5',5'',5''',6,6',6'',6'''-octaacetoxy-7,2':3',3'':2'',7'''-tetraindolyl (acetylated 8, 3%), 5,5',5'',5''',6,6',6'',6' ''-octaacetoxy-2,7':4',4'':7'',2'''-tetraindolyl (acetylated 9, 4%), and 5,5',5'',5''',6,6',6'',6'''-octaacetoxy-2,7':2',3'':2'',7'''-tetraindolyl (acetylated 10, 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 pi-electron conjugation or pi-stacked flat oligomer aggregates.
Pezzella
Alessandro
A
Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Via Cinthia 4, I-80126, Naples, Italy. alessandro.pezzella@unina.it
Panzella
Lucia
L
Natangelo
Anna
A
Arzillo
Marianna
M
Napolitano
Alessandra
A
d'Ischia
Marco
M
D000107:Acetylation; D019281:Dimerization; D006861:Hydrogen Peroxide / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008543:Melanins / Q000737:chemistry*; D008956:Models, Chemical; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry*; D013237:Stereoisomerism
C526724:5,5',6,6'-tetrahydroxy-2,7'-biindolyl; D007211:Indoles; D008543:Melanins; D011108:Polymers; C041877:eumelanin; D006861:Hydrogen Peroxide; D009195:Peroxidase; C033871:5,6-dihydroxyindole