DNA是生物体遗传信息的载体, 研究药物与DNA的相互作用对探讨其作用机理及新药的设计合成具有重要意义。 利用紫外吸收光谱技术, 微量量热法, 等温滴定量热法以及分子模拟技术研究了乌头碱在水溶液中的溶解行为, 探讨了乌头碱与粘虫DNA、 鲑鱼精DNA、 小牛胸腺DNA的相互作用。 实验发现, 乌头碱在水溶液中的溶解过程为准一级反应, 半衰期（t1/2）为0.691 h。 乌头碱分别与三种DNA作用均为体现出沟槽和表面两种结合形式: 沟槽结合时, 结合常数Ka1为105, 结合位点数为0.40~0.60, 且反应为焓驱动的自发过程; 表面结合时, 乌头碱分子仅与DNA表面发生作用而并未嵌到DNA分子的疏水部分, 结合常数Ka2为103, 结合位点较大。 分子模拟显示, 乌头碱均以氢键作用力结合在三种DNA分子的沟槽区, 且乌头碱分子中C8上的酯基对粘虫DNA, 鲑鱼精DNA和小牛胸腺DNA链上的碱基有特异性识别, 依次为T33, T34和G16, C9, C8。 模拟计算获得反应的结合能与实验测定所得ΔG值接近, 同时, 依据实验数据判定的作用力类型在分子模拟中得到印证, 即理论计算与实验基本吻合。

DNA is a vector for the genetic information of organisms. It is important to study the interaction between drugs and DNA and to explore its reaction mechanism, the design and synthesis of new drugs. The dissolution behavior of aconitine in water was studied for the first time by microcalorimetry. By using isothermal titration calorimetry, UV-Vis Absorption Spectroscopy and molecular simulation, the interaction between aconitine and armyworm DNA, salmon sperm DNA and calf thymus DNA was discussed. The results showed that the dissolution process of aconitine in aqueous solution was a simple first-order reaction and t1/2=0.691 h. There were two types of combinations during interactions between aconitine and the three different DNAs. The type Ⅰ combination was found to bean enthalpy-driven process. The equilibrium constant of combination (Ka1) was larger with the value of about 105. The number of binding sites (n1) was 0.40~0.60. The reaction took place in the groove areas. With regard to type II combination, the values of Ka2 was 103, and n2 was larger than n1. Lower equilibrium constant of combination demonstrated that the drug ligands just reacted with DNA on the surface instead of entering into the interior of macromolecules. Molecular simulation studies showed that the combination of aconitine and three DNAs occurred in the groove areas. The hydrogen bondwas mainly interactions during interactions between aconitine and the three different DNAs, and the ester groups on the C8 of the aconitine molecule were related to the armyworm DNA, the salmon sperm DNA and the calf thymus DNA respectively. Their bases were specifically identified by T33, T34 and G16, C9, C8. The similarity between the calculated binding energy and the measured ΔG demonstrated that the theoretical calculations were consistent with the experimental results. It can be seen that there is good agreement between the theoretical calculations and experimental results in this work.