【作者】 孙智； 刘永东； 钟儒刚；

【Author】 Zhi Sun,Yong Dong Liu,Ru Gang Zhong College of Life Science & Bioengineering,Beijing University of Technology,Beijing,100124,

【机构】 北京工业大学生命科学与生物工程学院；

【摘要】 人体内仲胺与活性氮氧化物N₂O₃的亚硝化反应与许多疾病的发生有关,其产物N-亚硝胺已被证明是一类具有强致癌性的化合物。因此,对于此亚硝化反应抑制剂的研究已受到普遍关注。本文选取二甲胺（DMA）与N₂O₃的反应体系为模型,采用密度泛函理论,在CCSD/6-311+G（d,p）//B3LYP/6-311+G（d,p）水平上研究发现CO₂能够抑制DMA与N₂O₃之间的亚硝化反应。其抑制机理如下图所示:（CH₃）₂NH+CO₂→（CH₃）₂NCOOH（?）（CH₃）₂NNO+HCO₃NODMA DMCA NDMA如图,DMA首先与CO₂分子反应生成中间体二甲基氨基甲酸（DMCA）,这一中间体再与N₂O₃分子反应生成致癌性N-亚硝基二甲胺（NDMA）。其中,DMCA与N₂O₃的反应为控速步骤,其反应势垒为30.35 kcal/mol。这一反应势垒显著高于DMA与N₂O₃直接反应生成NDMA的势垒。因此,CO₂能够抑制仲胺与N₂O₃的亚硝化反应,这一结论与实验结果一致。本研究将有助于研发有效的亚硝化反应抑制剂。更多还原

【Abstract】 N-nitrosation of secondary amines by N₂O₃ in vivo is relevant to many human diseases, and the product N-nitrosamines are a class of carcinogenic compounds.Therefore,many studies have focused on exploring effective methods to inhibit these N-nitrosation reactions.In present study,based on the Density Functional Theory（DFT）,the dimethylamine（DMA）/N₂O₃ reaction system was investigated at the CCSD/6-311+G（d,p）//B3LYP/6-311+G（d,p） level.It was found that carbon dioxide（CO₂） is capable of inhibiting the N-nitrosation of DMA by N₂O₃.The inhibitory mechanism is illustrated as below: As illustrated,DMA first react with CO₂ to give an intermediate dimethylcarbamic acid（DMCA）, which then reacts with N₂O₃ to form the carcinogenic N-nitrosodimethylamine（NDMA）.The reaction of DMCA and N₂O₃ was confirmed to be the rate-determining step,and the corresponding energy barrier was predicted to be 30.35 kcal/mol.This energy barrier is remarkably higher than the barrier of the direct reaction of DMA with N₂O₃ to give NDMA. Therefore,a conclusion can be drawn that CO₂ can inhibit the N-nitrosation of DMA by N₂O₃, and this conclusion is consistent with the experimental results.This work will be helpful to search and develop effective methods to inhibit the N-nitrosation reactions.更多还原