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  

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

作　　者：李澜[1] 王竑[1] 牛晓娟[2] 李宗和[3] 

机构地区：[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

出　　处：《高等学校化学学报》2009年第8期1596-1599,共4页Chemical Journal of Chinese Universities

基　　金：上海应用技术学院科研启动项目(批准号:YJ2007-36);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(-αhydroxylation-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.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 investi- gated 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.

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 

分 类 号：O641[理学—物理化学]