Development of Novel Antioxidants Based on Thermodynamic Parameters Calculated by Density Functional Theory

为了防止与生活方式相关的疾病、衰老以及辐射损伤，我们基于密度泛函理论计算，设计并合成了比天然抗氧化剂具有更低的酚羟基O-H离解能(D(HT))或电离势(IP)的酚类抗氧剂。与母体抗氧化剂相比，所得到的化合物显示出显著更高的自由基清除活性。计算的D(HT)或IP值越低，清除自由基的活性就越高。此外，部分化合物对大鼠胸腺细胞具有辐射防护作用，且无毒性。然而，没有观察到这些抗氧化剂清除自由基和辐射防护活性之间的相关性，这表明其他因素，如亲脂性，对使用这些化合物对细胞和动物是重要的。

To prevent life-style related diseases, senescence, as well as radiation damage, we designed and synthesized phenolic antioxidants with lower O-H dissociation energies (D(HT)) of the phenolic OH group or ionization potentials (IP) than natural antioxidants based on the density functional theory calculations. The compounds, thus obtained, showed significantly higher radical-scavenging activity as compared to parent antioxidants. The lower the calculated D(HT) or IP values is, the higher the radical-scavenging activity becomes. Furthermore, some of the compounds showed radioprotective activity toward rat thymocytes without toxicity. However, no correlation was observed between radical-scavenging and radioprotective activities of these antioxidants, indicating that other factors, such as lipophilicity, are important to use these compounds toward cells and animals.