title: Free radical coupling of o-semiquinones uncovered.
abstract: As a rule, o-semiquinones decay through disproportionation leading to equimolar amounts of catechol and o-quinone products. However, the o-semiquinone 1S generated by pulse radiolysis oxidation of the eumelanin precursor 5,6-dihydroxyindole (1) decays with second-order kinetics to generate broad visible chromophores that are incompatible with the predicted absorption of 5,6-indolequinone (1Q). Using an integrated chemical, pulse radiolytic and computational approach as well as deuterium labeling, we show herein that 1S and related 5,6-dihydroxyindole semiquinones decay mainly by a free radical coupling mechanism. This conclusion was supported by the inverse kinetic isotope effect observed with deuterated 1S, the identification of unprecedented dihydrobiindole products by one-electron oxidation of 1, the good matching of simulated absorption profiles of free radical coupling products of 1S with experimental spectra, and a detailed computational analysis of the kinetics and thermodynamics of the disproportionation equilibrium and free radical coupling of 1S versus 1-1Q coupling. These results disclose, to the best of our knowledge, the first example of free radical dimerization of o-semiquinones outcompeting the classic disproportionation-driven catechol-quinone coupling and suggest that this hitherto unrecognized process may be of broader relevance than previously believed.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, I-80126 Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pezzella
authors.forename: Orlando
authors.initials: O
authors.lastname: Crescenzi
authors.forename: Lucia
authors.initials: L
authors.lastname: Panzella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Napolitano
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Land
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barone
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
mesh_terms: D016227:Benzoquinones / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry*; D045563:Indolequinones / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D008543:Melanins / Q000737:chemistry; D010084:Oxidation-Reduction; D011675:Pulse Radiolysis
chemical_list: D016227:Benzoquinones; D005609:Free Radicals; D045563:Indolequinones; D007211:Indoles; D008543:Melanins; C041877:eumelanin; C025232:semiquinone radicals; C033871:5,6-dihydroxyindole