title: The "benzothiazine" chromophore of pheomelanins: a reassessment.
abstract: The characteristic absorption and photochemical properties of pheomelanins are generally attributed to "benzothiazine" structural units derived biogenetically from 5-S-cysteinyldopa. This notion, however, conveys little or no information about the structural chromophores responsible for the photoreactivity of pheomelanins. At pH 7.4, natural and synthetic pheomelanins show a defined maximum around 305 nm, which is not affected by reductive treatment with sodium borohydride, and a monotonic decrease in the absorption in the range 350-550 nm. These features are not compatible with a significant proportion of structural units related to 2H-1,4-benzothiazine and 2H-1,4-benzothiazine-3-carboxylic acid, the early borohydride-reducible pheomelanin precursors featuring absorption maxima above 340 nm. Rather, these features would better accommodate a contribution by the nonreducible 3-oxo-3,4-dihydrobenzothiazine (lambdamax 299 nm) and benzothiazole (lambdamax 303 nm) structural motifs, which are generated in the later stages of pheomelanogenesis in vitro. This conclusion is supported by a detailed liquid chromatography/UV and mass spectrometry monitoring of the species formed in the oxidative conversion of 5-S-cysteinyldopa to pheomelanin, and would point to a critical reassessment of the commonly reported "benzothiazine" chromophore in terms of more specific and substantiated structural units, like those formed during the later stages of pheomelanin synthesis in vitro.
authors.affiliation: Department of Organic Chemistry and Biochemistry, University of Naples Federico II Complesso Universitario, Monte S. Angelo, Naples, Italy. alesnapo@unina.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Napolitano
authors.forename: Maria
authors.initials: M
authors.lastname: De Lucia
authors.forename: Lucia
authors.initials: L
authors.lastname: Panzella
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003548:Cysteinyldopa / Q000737:chemistry*; D008543:Melanins / Q000737:chemistry*; D008547:Melanophores / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013056:Spectrophotometry, Ultraviolet; D013843:Thiazines / Q000737:chemistry*
chemical_list: C446962:1,4-benzothiazine; D008543:Melanins; D013843:Thiazines; C018362:pheomelanin; D003548:Cysteinyldopa