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 d istinctive pigments of red human hair, arise by oxidative cyclization of cy steinyldopas mainly 5-S-cysteinyldopa (1) via a critical o-quinonimine inte rmediate, which rearranges to unstable 1,4-benzothiazines. To get new evide nce for these labile species, fast time resolution pulse radiolytic oxidati on by dibromide radical anion of a suitable precursor, the dihydro-1,4-benz othiazine-3-carboxylic acid 7 was performed in comparison with that of 1. I n the case of 7, dibromide radical anion oxidation leads over a few microse conds (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 w ith second-order kinetics (2k = 2.7 X 10(7) M-1 s(-1)) to a species exhibit ing an absorption maximum at 540 nm (epsilon = 2200 M-1 cm(-1)). This was f ormulated as the o-quinonimine 3 arising from disproportionation of the ini tial radical. The quinonimine chromophore is converted over hundreds of mil liseconds (k = 6.0 s(-1)) to a broad maximum at around 330 nm interpreted a s due to a 1,4-benzothiazine or a mixture of 1,4-benzothiazines, which as e xpected are unstable and subsequently decay over a few seconds (k = 0.5 s(- 1)). Interestingly, the quinonimine is observed as a labile intermediate al so in the alternative reaction route examined, involving cyclization of the o-quinone (lambda(max) 390 nm, epsilon = 6900 M-1 cm(-1)) arising by dispr oportionation (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 spectropho tometric monitoring of the ferricyanide oxidation of a series of model dihy drobenzothiazines. (C) 1999 Elsevier Science Inc.