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

为了预防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，设计并合成了具有比天然抗氧化剂更低的酚羟基的O-H解离能（D（HT））或电离势（IP）的酚类抗氧化剂。 由此获得的化合物，显示出显着更高的自由基清除活性相比，母体抗氧化剂。 计算的D（HT）或IP值越低，自由基清除活性变得越高。 此外，一些化合物对大鼠胸腺细胞显示出辐射保护活性，而没有毒性。 然而，没有观察到这些抗氧化剂的自由基清除和辐射防护活性之间的相关性，这表明其他因素，如亲脂性，是重要的使用这些化合物对细胞和动物。

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.