加入抗坏血酸清除烷基过氧自由基:电子转移的替代机制。

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Antioxidants Pub Date : 2024-10-01 DOI:10.3390/antiox13101194
Gabriel Robert, J Richard Wagner
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引用次数: 0

摘要

维生素 C(抗坏血酸;Asc)是一种重要的生物抗氧化剂,可清除活性氧,如有害的烷基过氧自由基(ROO-),这些自由基是生物大分子在氧气存在下通过自由基介导的氧化作用产生的。Asc 的自由基捕获特性通常归因于其与活性物种发生单电子转移的能力。根据这一机制,Asc 与 ROO- 反应后会形成脱氢抗坏血酸(DHA)和相应的氢过氧化物(ROOH)。在研究 DNA 5-(2'-脱氧尿苷基)甲基过氧自由基的反应性时,我们发现了 Asc 清除 ROO- 的新途径。本研究的目的是阐明这一反应的基本机理,重点是分析中间和最终分解产物的特征。我们的研究表明,Asc 清除 ROO- 的过程中会形成一种醇(ROH)和一种不稳定的环状草酰-L-苏氨酸中间体(cOxa-Thr),这种中间体很容易水解成一系列开链草酰-L-苏氨酸半异构体。通过详细的 MS 和 NMR 分析确定了产物的结构。Asc 的 C2=C3 烯二醇部分最初可通过过氧自由基加成(PRA)来解释上述转化。生成的加合物自由基被氧化后,产物随后发生拜耳-维利格重排,释放出 ROH 并生成扩环产物 cOxa-Thr。本研究有力地阐明了过氧化物介导的 Asc 和 DHA 氧化化学反应,过去由于自氧化反应的干扰以及氧化产物分析和表征的困难,这些化学反应在很大程度上被掩盖了。PRA 清除 Asc 上的 ROO- 可能会产生有益的结果,因为它能直接将 ROO- 转化为 ROH,从而防止形成可能有害的 ROOH,尽管它会诱导 Asc 分解为草酰苏氨酸片段。
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Scavenging of Alkylperoxyl Radicals by Addition to Ascorbate: An Alternative Mechanism to Electron Transfer.

Vitamin C (ascorbate; Asc) is a biologically important antioxidant that scavenges reactive oxygen species such as deleterious alkylperoxyl radicals (ROO), which are generated by radical-mediated oxidation of biomolecules in the presence of oxygen. The radical trapping proprieties of Asc are conventionally attributed to its ability to undergo single-electron transfers with reactive species. According to this mechanism, the reaction between Asc and ROO results in the formation of dehydroascorbate (DHA) and the corresponding hydroperoxides (ROOH). When studying the reactivity of DNA 5-(2'-deoxyuridinyl)methylperoxyl radicals, we discovered a novel pathway of ROO scavenging by Asc. The purpose of this study is to elucidate the underlying mechanism of this reaction with emphasis on the characterization of intermediate and final decomposition products. We show that the trapping of ROO by Asc leads to the formation of an alcohol (ROH) together with an unstable cyclic oxalyl-l-threonate intermediate (cOxa-Thr), which readily undergoes hydrolysis into a series of open-chain oxalyl-l-threonic acid regioisomers. The structure of products was determined by detailed MS and NMR analyses. The above transformation can be explained by initial peroxyl radical addition (PRA) onto the C2=C3 enediol portion of Asc. Following oxidation of the resulting adduct radical, the product subsequently undergoes Baeyer-Villiger rearrangement, which releases ROH and generates the ring expansion product cOxa-Thr. The present investigation provides robust clarifications of the peroxide-mediated oxidation chemistry of Asc and DHA that has largely been obscured in the past by interference with autooxidation reactions and difficulties in analyzing and characterizing oxidation products. Scavenging of ROO by PRA onto Asc may have beneficial consequences since it directly converts ROO into ROH, which prevents the formation of potentially deleterious ROOH, although it induces the breakdown of Asc into fragments of oxalyl-l-threonic acid.

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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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