过氧亚硝酸与酪氨酸的反应机理

Mechanisms of the Reaction of Peroxynitrous Acid and Tyrosine

用密度泛函理论(DFT)研究了过氧亚硝酸与酪氨酸的反应机理.在B3LYP/6-311G(d,p)水平上对该反应体系的反应物、中间体、过渡态和产物进行了几何构型优化并计算了振动频率和能量.计算结果表明,过氧亚硝酸不易直接与酪氨酸反应,而是先分解产生自由基(·OH和·NO2),而后再与酪氨酸分步作用.过氧亚硝酸与酪氨酸的反应生成两种主要产物,分别为3-羟基酪氨酸和3-硝基酪氨酸,这一结论与实验所得到的结果一致.此外在同一计算水平上采用SCRF(PCM)方法计算了溶剂化效应,结果表明,极性溶剂可以增加自由基结合的稳定化能,并降低反应通道的活化能,有利于反应的进行.

The mechanisms of the reaction of peroxynitrous acid and tyrosine were studied using the density functional theory （DFT） at B3LYP/6-311G（d,p） level. The geometries of all the molecules were optimized; the harmonic vibration frequencies and the energies were calculated as well. The calculation results showed that stepwise mechanism rather than concerted mechanism was preferred for the reaction of peroxynitrous acid and tyrosine. The stepwise pathway started with homolysis of the HO--ONO bond to discrete · OH and · NO2 radicals, which then reacted with tyrosine v/a two different pathways： （i） the H atom of tyrosine hydroxyl was abstracted by -OH to produce IM3, which then combined with · NO2 forming the intermediate （IM1）. Subsequently, the IM1 underwent further transformation leading to the product of 3-nitrotyrosine. （ii） the · OH was added to the phenol ring of tyrosine to produce the IM2, which then combined with · NO2 forming the intermediate （IM21）. The IM21 also underwent further transformation leading to the product of 3-hydroxytyrosine. The activation energies of the rate-determining steps of these two pathways were 82.86 and 48.05 kJ·mol^-1, respectively. This conclusion was in good agreement with the corresponding experimental data. Additionally, effects of aqueous solvation of water on this reaction were also investigated and the results indicated that the reaction preferably took place in water.