褐黑素生成过程中的瞬态醌亚胺和1,4-苯并噻嗪：新的脉冲辐射分解和分光光度法证据

Transient quinonimines and 1,4-benzothiazines of pheomelanogenesis: new pulse radiolytic and spectrophotometric evidence.

作者信息

Napolitano A, Di Donato P, Prota G, Land E J

机构信息

The Department of Organic and Biological Chemistry, University of Naples Federico II, Italy.

出版信息

Free Radic Biol Med. 1999 Sep;27(5-6):521-8. doi: 10.1016/s0891-5849(99)00098-2.

DOI:10.1016/s0891-5849(99)00098-2

PMID:10490271

Abstract

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.

摘要

生物合成和体外模型研究表明，褐黑素是人类红色头发的独特色素，主要由半胱氨酰多巴（尤其是5-S-半胱氨酰多巴（1））通过关键的邻醌亚胺中间体进行氧化环化生成，该中间体重排为不稳定的1,4-苯并噻嗪。为了获得这些不稳定物种的新证据，通过二溴化物自由基阴离子对合适的前体二氢-1,4-苯并噻嗪-3-羧酸7进行快速时间分辨脉冲辐射氧化，并与1进行比较。对于7，二溴化物自由基阴离子氧化在几微秒内（k = 2.1 x 10⁹ M⁻¹ s⁻¹）导致生成一个苯氧基自由基（λmax 330 nm，ε = 6300 M⁻¹ cm⁻¹），该自由基在几十毫秒内以二级动力学（2k = 2.7 x 10⁷ M⁻¹ s⁻¹）生成一个在540 nm处有吸收最大值的物种（ε = 2200 M⁻¹ cm⁻¹）。这被确定为由初始自由基歧化产生的邻醌亚胺3。醌亚胺发色团在数百毫秒内（k = 6.0 s⁻¹）转化为在330 nm左右的一个宽峰，这被解释为由于一种1,4-苯并噻嗪或多种1,4-苯并噻嗪的混合物，正如预期的那样，它们是不稳定的，随后在几秒钟内衰变（k = 0.5 s⁻¹）。有趣的是，在研究的另一条反应途径中也观察到醌亚胺是一种不稳定的中间体，该途径涉及由二溴化物自由基阴离子氧化1直接生成的邻半醌（λmax 320 nm，ε = 4700 M⁻¹ cm⁻¹）歧化（2k = 1.7 x 10⁸ M⁻¹ s⁻¹）产生的邻醌（λmax 390 nm，ε = 6900 M⁻¹ cm⁻¹）的环化。通过对一系列模型二氢苯并噻嗪的铁氰化物氧化进行快速扫描二极管阵列分光光度监测，进一步支持了将540 nm物种结构确定为邻醌亚胺的结论。