Transient quinonimines and 1,4-benzothiazines of pheomelanogenesis: new pulse radiolytic and spectrophotometric evidence.
Biosynthetic and model in vitro studies have shown that pheomelanins, the distinctive pigments of red human hair, arise by oxidative cyclization of cysteinyldopas mainly 5-S-cysteinyldopa (1) via a critical o-quinonimine intermediate, which rearranges to unstable 1,4-benzothiazines. To get new evidence for these labile species, fast time resolution pulse radiolytic oxidation by dibromide radical anion of a suitable precursor, the dihydro-1,4-benzothiazine-3-carboxylic acid 7 was performed in comparison with that of 1. In the case of 7, dibromide radical anion oxidation leads over a few microseconds (k = 2.1 x 10(9) M(-1) s(-1)) to a phenoxyl radical (lambda(max) 330 nm, epsilon = 6300 M(-1) cm(-1)) which within tens of milliseconds gives rise with second-order kinetics (2k = 2.7 x 10(7) M(-1) s(-1)) to a species exhibiting an absorption maximum at 540 nm (epsilon = 2200 M(-1) cm(-1)). This was formulated as the o-quinonimine 3 arising from disproportionation of the initial radical. The quinonimine chromophore is converted over hundreds of milliseconds (k = 6.0 s(-1)) to a broad maximum at around 330 nm interpreted as due to a 1,4-benzothiazine or a mixture of 1,4-benzothiazines, which as expected are unstable and subsequently decay over a few seconds (k = 0.5 s(-1)). Interestingly, the quinonimine is observed as a labile intermediate also in the alternative reaction route examined, involving cyclization of the o-quinone (lambda(max) 390 nm, epsilon = 6900 M(-1) cm(-1)) arising by disproportionation (2k = 1.7 x 10(8) M(-1) s(-1)) of an o-semiquinone (lambda(max) 320 nm, epsilon = 4700 M(-1) cm(-1)) directly generated by dibromide radical anion oxidation of 1. Structural formulation of the 540 nm species as an o-quinonimine was further supported by rapid scanning diode array spectrophotometric monitoring of the ferricyanide oxidation of a series of model dihydrobenzothiazines.
Napolitano
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The Department of Organic and Biological Chemistry, University of Naples Federico II, Italy.
Di Donato
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P
Prota
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Land
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EJ
D017484:Dermatitis, Phototoxic; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D005292:Ferricyanides / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D006200:Hair Color; D006801:Humans; D007700:Kinetics; D008543:Melanins / Q000096:biosynthesis* / Q000737:chemistry; D015394:Molecular Structure; D010860:Pigments, Biological / Q000737:chemistry; D011675:Pulse Radiolysis; D011809:Quinones / Q000737:chemistry*; D013053:Spectrophotometry; D013843:Thiazines / Q000737:chemistry*
C092922:5-S-cysteinyl-3,4-dihydroxyphenylalanine; D005292:Ferricyanides; D005609:Free Radicals; D008543:Melanins; D010860:Pigments, Biological; D011809:Quinones; D013843:Thiazines; C018362:pheomelanin; C007931:hexacyanoferrate III; D004295:Dihydroxyphenylalanine