Robert Gabriel, Wagner J Richard
Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Antioxidants (Basel). 2024 Oct 1;13(10):1194. doi: 10.3390/antiox13101194.
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.
维生素C（抗坏血酸盐；Asc）是一种具有重要生物学意义的抗氧化剂，它能清除活性氧物种，如有害的烷基过氧自由基（ROO），这些自由基是在氧气存在下由生物分子的自由基介导氧化产生的。Asc的自由基捕获特性通常归因于其与活性物种进行单电子转移的能力。根据这一机制，Asc与ROO之间的反应会导致脱氢抗坏血酸（DHA）和相应的氢过氧化物（ROOH）的形成。在研究DNA 5-（2'-脱氧尿苷基）甲基过氧自由基的反应活性时，我们发现了Asc清除ROO的一条新途径。本研究的目的是阐明该反应的潜在机制，重点是中间体和最终分解产物的表征。我们表明，Asc捕获ROO会导致形成一种醇（ROH）以及一种不稳定的环状草酰-L-苏糖酸中间体（cOxa-Thr），该中间体很容易水解成一系列开链草酰-L-苏糖酸区域异构体。通过详细的质谱和核磁共振分析确定了产物的结构。上述转化可以通过初始过氧自由基加成（PRA）到Asc的C2 = C3烯二醇部分来解释。在所得加合物自由基氧化后，产物随后经历拜耳-维利格重排，释放出ROH并生成环扩张产物cOxa-Thr。本研究为Asc和DHA的过氧化物介导的氧化化学提供了有力的阐释，过去由于自动氧化反应的干扰以及氧化产物分析和表征的困难，这一化学过程在很大程度上被掩盖了。通过PRA将ROO加成到Asc上进行清除可能会产生有益的结果，因为它直接将ROO转化为ROH，这可以防止潜在有害的ROOH的形成，尽管它会导致Asc分解成草酰-L-苏糖酸片段。
