5-溴尿嘧啶 - CAS号 51-20-7

物化性质

熔点：

>300 °C (lit.)
密度：

1.8710 (rough estimate)
溶解度：

<1g/l
物理描述：

5-bromouracil is a white powder. (NTP, 1992)
颜色/状态：

Prisms from water
蒸汽压力：

2.27X10-7 mm Hg at 25 °C (est)
分解：

When heated to decomposition it emits very toxic fumes of /hydrogen bromide and nitrogen oxide/.

计算性质

辛醇/水分配系数(LogP)：

-0.2
重原子数：

9
可旋转键数：

0
环数：

1.0
sp3杂化的碳原子比例：

0.0
拓扑面积：

58.2
氢给体数：

2
氢受体数：

2

ADMET

代谢

嗜酸性粒细胞使用嗜酸性粒细胞过氧化物酶、过氧化氢（H2O2）和溴离子（Br-）生成次溴酸（HOBr），这是一种溴化中间体。这种强氧化剂可能在宿主防御入侵寄生虫和嗜酸性粒细胞介导的组织损伤中发挥作用。在本研究中，作者们探讨了嗜酸性粒细胞过氧化物酶产生的HOBr可能氧化核酸的可能性。当作者们将尿嘧啶、尿苷或脱氧尿苷暴露于试剂HOBr时，每个反应混合物都产生了一个主要氧化产物，该产物在反相高效液相色谱上与相应的溴化嘧啶共迁移。嗜酸性粒细胞过氧化物酶-H2O2-Br-系统也将尿嘧啶转化为一个主要氧化产物，并且产量接近定量。质谱、高效液相色谱、紫外-可见光谱和核磁共振光谱鉴定产物为5-溴尿嘧啶。嗜酸性粒细胞过氧化物酶需要H2O2和Br-来产生5-溴尿嘧啶，表明HOBr是该反应的中间体。初级和次级溴胺也能溴化尿嘧啶，这表明长寿命的溴胺也可能是有生理相关性的溴化中间体。人嗜酸性粒细胞使用嗜酸性粒细胞过氧化物酶-H2O2-Br-系统氧化尿嘧啶。通过质谱、高效液相色谱和紫外-可见光谱鉴定产物为5-溴尿嘧啶。总的来说，这些结果表明嗜酸性粒细胞过氧化物酶产生的HOBr将尿嘧啶氧化为5-溴尿嘧啶。胸腺嘧啶磷酸化酶，一种嘧啶挽救酶，将5-溴尿嘧啶转化为5-溴脱氧嘧啶，这是胸腺嘧啶的致突变类似物。这些发现提出了嗜酸性粒细胞过氧化物酶产生的卤化核苷酸可能在嗜酸性粒细胞丰富的炎症部位产生细胞毒性和突变效应的可能性。

Eosinophils use eosinophil peroxidase, hydrogen peroxide (H(2)O(2)), and bromide ion (Br(-)) to generate hypobromous acid (HOBr), a brominating intermediate. This potent oxidant may play a role in host defenses against invading parasites and eosinophil-mediated tissue damage. In this study, /the authors/ explore the possibility that HOBr generated by eosinophil peroxidase might oxidize nucleic acids. When /the authors/ exposed uracil, uridine, or deoxyuridine to reagent HOBr, each reaction mixture yielded a single major oxidation product that comigrated on reversed-phase HPLC with the corresponding authentic brominated pyrimidine. The eosinophil peroxidase-H(2)O(2)-Br(-) system also converted uracil into a single major oxidation product, and the yield was near-quantitative. Mass spectrometry, HPLC, UV--visible spectroscopy, and NMR spectroscopy identified the product as 5-bromouracil. Eosinophil peroxidase required H(2)O(2) and Br(-) to produce 5-bromouracil, implicating HOBr as an intermediate in the reaction. Primary and secondary bromamines also brominated uracil, suggesting that long-lived bromamines also might be physiologically relevant brominating intermediates. Human eosinophils used the eosinophil peroxidase-H(2)O(2)-Br(-) system to oxidize uracil. The product was identified as 5-bromouracil by mass spectrometry, HPLC, and UV--visible spectroscopy. Collectively, these results indicate that HOBr generated by eosinophil peroxidase oxidizes uracil to 5-bromouracil. Thymidine phosphorylase, a pyrimidine salvage enzyme, transforms 5-bromouracil to 5-bromodeoxyridine, a mutagenic analogue of thymidine. These findings raise the possibility that halogenated nucleobases generated by eosinophil peroxidase exert cytotoxic and mutagenic effects at eosinophil-rich sites of inflammation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

使用一种灵敏且特异性的质谱方法，作者在富含中性粒细胞的人类炎症组织中检测到了两种髓过氧化物酶的产物，5-氯尿嘧啶和5-溴尿嘧啶。髓过氧化物酶很可能是体内5-氯尿嘧啶的来源，因为卤化尿嘧啶是髓过氧化物酶系统在体外的特异性产物。相比之下，以前的研究已经证明，5-溴尿嘧啶可能由嗜酸性粒细胞过氧化物酶或髓过氧化物酶生成，这两种酶在卤化物血浆浓度下和适度酸性条件下优先对尿嘧啶进行溴化。这些观察结果表明，髓过氧化物酶系统在体内促进了核苷酸的卤化。由于5-氯尿嘧啶和5-溴尿嘧啶可以并入核DNA中，并且这些胸腺嘧啶类似物是已知的诱变剂，我们的观察结果提出了嗜中性粒细胞启动的卤化反应可能是炎症部位突变和细胞毒性的一个途径的可能性。

... Using a sensitive and specific mass spectrometric method, /the authors/ detected two products of myeloperoxidase, 5-chlorouracil and 5-bromouracil, in neutrophil-rich human inflammatory tissue. Myeloperoxidase is the most likely source of 5-chlorouracil in vivo because halogenated uracil is a specific product of the myeloperoxidase system in vitro. In contrast, previous studies have demonstrated that 5-bromouracil could be generated by either eosinophil peroxidase or myeloperoxidase, which preferentially brominates uracil at plasma concentrations of halide and under moderately acidic conditions. These observations indicate that the myeloperoxidase system promotes nucleobase halogenation in vivo. Because 5-chlorouracil and 5-bromouracil can be incorporated into nuclear DNA, and these thymine analogs are well known mutagens, our observations raise the possibility that halogenation reactions initiated by phagocytes provide one pathway for mutagenesis and cytotoxicity at sites of inflammation.

来源:Hazardous Substances Data Bank (HSDB)

代谢

5-溴尿嘧啶通过胸腺嘧啶磷酸化酶代谢成5-溴脱氧尿苷。

5-bromouracil is metabolized into 5-bromodeoxyuridine via thymidine phosphorylase. (L626)