Site of Azido Substitution in the Sugar Moiety of Azidopyrimidine Nucleosides Influences the Reactivity of Aminyl Radicals Formed by Dissociative Electron Attachment.
Site of Azido Substitution in the Sugar Moiety of Azidopyrimidine Nucleosides Influences the Reactivity of Aminyl Radicals Formed by Dissociative Electron Attachment.
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叠氮二嘧啶核苷的糖部分中叠氮化物的位点会影响解离电子附着形成的氨基基自由基的反应性。
DOI：
10.1021/acs.jpcb.0c08201
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发表时间：
2020-12-17
期刊：
影响因子：
--
通讯作者：
Adhikary A
中科院分区：
文献类型：
--
作者：
Mudgal M;Dang TP;Sobczak AJ;Lumpuy DA;Dutta P;Ward S;Ward K;Alahmadi M;Kumar A;Sevilla MD;Wnuk SF;Adhikary A
在这项工作中，电子诱导的中性π型氨基自由基（RNH·）的位点特异性形成及其与糖部分中不同位置处的叠氮标记的嘧啶核苷类似物的反应，例如，在2′-、3′-、4′-和5′-位沿着与模型化合物3-叠氮基-1-丙醇（3AZPrOH）反应。电子顺磁共振（EPR）研究证实了RNH·的形成位点和机制，通过解离电子附着介导的N2损失和随后的质子化从溶剂中使用15 N-标记的叠氮基，在糖和碱的特定位点的氘代，以及将溶剂从H2O变为D2 O。用EPR方法研究了RNH·的反应。17万RNH·在主碳位（5′-叠氮基-2 ′，5 ′-双脱氧尿苷，3AZPrOH）通过双分子H原子夺取形成α-叠氮烷基容易地转化为σ-型亚胺基（R=N·）。RNH·当在第二碳位点时（例如，2′-叠氮基-2 ′-脱氧尿苷）与邻近嘧啶碱基的C5=C6双键发生双分子亲电加成反应。最后，叔烷基碳（4′-叠氮胞苷）上的RNH·几乎不发生反应。这些结果显示了立体化学和电子环境对RNH·反应性的影响，并允许选择那些在增强细胞辐射损伤中最有效的叠氮苷。
In this work, electron-induced site-specific formation of neutral π-type aminyl radicals (RNH•) and their reactions with pyrimidine nucleoside analogs azidolabeled at various positions in the sugar moiety, e.g., at 2′-, 3′-, 4′-, and 5′- sites along with a model compound 3-azido-1-propanol (3AZPrOH), were investigated. Electron paramagnetic resonance (EPR) studies confirmed the site and mechanism of RNH• formation via dissociative electron attachment-mediated loss of N2 and subsequent facile protonation from the solvent employing 15N-labeled azido group, deuterations at specific sites in the sugar and base, and changing the solvent from H2O to D2O. Reactions of RNH• were investigated employing EPR by warming these samples from 77 K to ca. 170 K. RNH• at a primary carbon site (5′-azido-2′,5′-dideoxyuridine, 3AZPrOH) facilely converted to a σ-type iminyl radical (R=N•) via a bimolecular H-atom abstraction forming an α-azidoalkyl radical. RNH• when at a secondary carbon site (e.g., 2′-azido-2′-deoxyuridine) underwent bimolecular electrophilic addition to the C5=C6 double bond of a proximate pyrimidine base. Finally, RNH• at tertiary alkyl carbon (4′-azidocytidine) underwent little reaction. These results show the influence of stereochemical and electronic environment on RNH• reactivity and allow the selection of those azidonucleosides that would be most effective in augmenting cellular radiation damage.
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影响因子：
15
作者：
Adhikary A;Kumar A;Khanduri D;Sevilla MD
通讯作者：
Sevilla MD
影响因子：
15
作者：
Adhikary A;Khanduri D;Sevilla MD
通讯作者：
Sevilla MD
影响因子：
5.7
作者：
Banyasz, Akos;Ketola, Tiia-Maaria;Munoz-Losa, Aurora;Rishi, Sunny;Adhikary, Amitava;Sevilla, Michael D.;Martinez-Fernandez, Lara;Improta, Roberto;Markovitsi, Dimitra
通讯作者：
Markovitsi, Dimitra
影响因子：
3.3
作者：
Gai, Xin Sonia;Fenlon, Edward E.;Brewer, Scott H.
通讯作者：
Brewer, Scott H.
影响因子：
3.5
作者：
Jagetia, GC;Aruna, R
通讯作者：
Aruna, R