DICP OpenIR
Formation of Guanine-6-sulfonate from 6-Thioguanine and Singlet Oxygen: A Combined Theoretical and Experimental Study
Zou, Xiaoran; Zhao, Hongmei; Yu, Youqing; Su, Hongmei
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
2013-03-20
DOI10.1021/ja400483j
135期:11页:4509-4515
收录类别SCI
文章类型Article
WOS标题词Science & Technology ; Physical Sciences
类目[WOS]Chemistry, Multidisciplinary
研究领域[WOS]Chemistry
关键词[WOS]DENSITY-FUNCTIONAL THEORY ; DNA-DAMAGE ; MOLECULAR-OXYGEN ; PROTON-TRANSFER ; CROSS-LINKING ; UVA LIGHT ; BASE-PAIR ; DEACTIVATION ; AZATHIOPRINE ; CELLS
英文摘要As an end metabolism product of the widely used thiopurine drugs, 6-thioguanine (6-TG) absorbs UVA and produces O-1(2) by photosensitization. This unusual photochemical property triggers a variety of DNA damage, among which the oxidation of 6-TG itself by O-1(2) to the promutagenic product guanine-6-sulfonate (G(SO3)) represents one of the major forms. It has been suspected that there exists an initial intermediate, G(SO), prior to its further oxidation to G(SO2) and G(SO3), but G(SO) has never been observed. Using density functional theory, we have explored the energetics and intermediates of 6-TG and O-1(2). A new mechanism via G(SOOH) -> G(SO2) -> G(SO4) -> G(SO3) has been discovered to be the most feasible energetically, whereas the anticipated G(SO) mechanism is found to encounter an inaccessibly high barrier and thus is prevented. The mechanism through the G(SOOH) and G(SO4) intermediates can be validated further by joint experimental measurements, where the fast rate constant of 4.9 X 10(9) M-1 s(-1) and the reaction stoichiometry of 0.58 supports this low-barrier new mechanism. In addition to the dominant pathway of G(SOOH) -> G(SO2) -> G(SO4) -> G(SO3), a side pathway with higher barrier, G(SOOH) -> G, has also been located, providing a rationalization for the observed product distributions of G(SO2) and G(SO3) as major products and G as minor product. From mechanistic and kinetics points of view, the present findings provide new chemical insights to understand the high phototoxicity of 6-TG in DNA and point to methods of using 6-TG as a sensitive fluorescence probe for the quantitative detection of O-1(2), which holds particular promise for detecting O-1(2) in DNA-related biological surroundings.
语种英语
WOS记录号WOS:000316774100046
引用统计
被引频次:20[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/137967
专题中国科学院大连化学物理研究所
作者单位Chinese Acad Sci, Inst Chem, State Key Lab Mol React Dynam, BNLMS, Beijing 100190, Peoples R China
推荐引用方式
GB/T 7714
Zou, Xiaoran,Zhao, Hongmei,Yu, Youqing,et al. Formation of Guanine-6-sulfonate from 6-Thioguanine and Singlet Oxygen: A Combined Theoretical and Experimental Study[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2013,135(11):4509-4515.
APA Zou, Xiaoran,Zhao, Hongmei,Yu, Youqing,&Su, Hongmei.(2013).Formation of Guanine-6-sulfonate from 6-Thioguanine and Singlet Oxygen: A Combined Theoretical and Experimental Study.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,135(11),4509-4515.
MLA Zou, Xiaoran,et al."Formation of Guanine-6-sulfonate from 6-Thioguanine and Singlet Oxygen: A Combined Theoretical and Experimental Study".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 135.11(2013):4509-4515.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Zou, Xiaoran]的文章
[Zhao, Hongmei]的文章
[Yu, Youqing]的文章
百度学术
百度学术中相似的文章
[Zou, Xiaoran]的文章
[Zhao, Hongmei]的文章
[Yu, Youqing]的文章
必应学术
必应学术中相似的文章
[Zou, Xiaoran]的文章
[Zhao, Hongmei]的文章
[Yu, Youqing]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。