高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (8): 1596.

• 研究论文 • 上一篇    下一篇

α-羟基化吡咯烷亚硝胺代谢及形成DNA加合物反应机理的理论研究

李澜1, 王竑1, 牛晓娟2, 李宗和3   

  1. 1. 上海应用技术学院数理部, 上海 200235;
    2. 江汉大学物理与信息工程学院物理系, 武汉 430056;
    3. 北京师范大学化学学院, 北京 100875
  • 收稿日期:2008-04-25 出版日期:2009-08-10 发布日期:2009-08-10
  • 通讯作者: 李澜, 女, 博士, 讲师, 主要从事分子反应动态学研究. E-mail: lilansit@yahoo.com.cn
  • 基金资助:

    上海应用技术学院科研启动项目(批准号: YJ2007-36)和上海市教委项目(批准号: YYY-07015)资助.

Theoretical Study of the Reaction Mechanism for the Formation of DNA Adducts by α-Hydroxy-nitrosopyrrolidine

LI Lan1*, WANG Hong1, NIU Xiao-Juan2, LI Zong-He3   

  1. 1. Department of Mathematic and Physics, Shanghai Institute of Technolgy, Shanghai 200235, China;
    2. School of Physics & Information Engineering, Jianghan University, Wuhan 430056, China;
    3. Department of Chemistry, Beijing Normal University, Beijing 100875, China
  • Received:2008-04-25 Online:2009-08-10 Published:2009-08-10
  • Contact: LI Lan. E-mail: lilansit@yahoo.com.cn
  • Supported by:

    上海应用技术学院科研启动项目(批准号: YJ2007-36)和上海市教委项目(批准号: YYY-07015)资助.

摘要:

采用密度泛函理论, 在B3LYP/6-31G**水平上, 研究了气相和水溶剂中, α-羟基化吡咯烷亚硝胺(α-hydroxylation-NPYR, A)代谢为终致癌物重氮氢氧化物(B)、重氮烷阳离子(C)和氧离子(D), 以及C与鸟嘌呤碱基相互作用的反应机理. 化合物A代谢为终致癌物, 涉及异构化和质子化过程, 是相对容易进行的放热反应. 终致癌物C与鸟嘌呤在N7位形成DNA加合物F和G的反应, 遵循SN2机理. 加合物G由F异构形成, 且有相对高的异构化能(气相: 244.77 kJ/mol; 水溶剂中: 234.83 kJ/mol), 这与实验上得到加合物G是主要癌变物的结果一致.

关键词: α-羟基化吡咯烷亚硝胺; 密度泛函理论; DNA加合物; 致癌

Abstract:

The reaction mechanism for the formation of ultimate carcinogens diazohydroxide(B), diazonium(C) and oxoniumions(D) by α-hydroxylation-NPYR and the alkylation process of C and guanine were investigated including solvent effects at the B3LYP/6-31G** level. The formation of ultimate carcinogens involves isomerization and protonation. And the process is relatively easy to occur. The alkylation reaction by ultimate carcinogen C and N7 site of guanine is an SN2 process, and forms DNA adduct F and G. Adduct G is isomerized by F. The isomerization energies are relatively high(in the gas phase: 244.77 kJ/mol; in solvent of water: 234.83 kJ/mol), which is consistent with the experiment that adduct F is the primary alkylation product.

Key words: α-Hydroxy-nitrosopyrrolidine; Density functional theory; DNA adduct; Carcinogen

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