Hussain Helmi H, Babic Gordana, Durst Tony, Wright James S, Flueraru Mihaela, Chichirau Alexandru, Chepelev Leonid L
Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie Street, Ottawa, Canada K1N 6N5.
J Org Chem. 2003 Sep 5;68(18):7023-32. doi: 10.1021/jo0301090.
We are attempting to develop novel synthetic antioxidants aimed at retarding the effects of free-radical induced cell damage. In this paper we discuss the design strategy and report the synthesis of seven novel antioxidants, including six catechols and a benzylic phenol. The bond dissociation enthalpy (BDE) for the most active (weakest) OH bond in each molecule was calculated by theoretical methods, as well as the BDE for the semiquinone radical. Reaction rates with the nitrogen-centered free radical DPPH() were measured in ethyl acetate. The log of k(DPPH) for bimolecular reaction correlated well with the primary BDE. The correlation between rate constants and calculated BDEs shows that the BDE is a good predictor of antioxidant activity with DPPH(), suggesting that our design criteria are useful and that these compounds should undergo further testing in cell cultures and in animal models.
我们正在尝试开发新型合成抗氧化剂，旨在延缓自由基诱导的细胞损伤效应。在本文中，我们讨论了设计策略并报告了七种新型抗氧化剂的合成，其中包括六种儿茶酚和一种苄基酚。通过理论方法计算了每个分子中最活泼（最弱）的OH键的键解离焓（BDE）以及半醌自由基的BDE。在乙酸乙酯中测量了与以氮为中心的自由基DPPH（）的反应速率。双分子反应的k（DPPH）的对数与主要BDE相关性良好。速率常数与计算出的BDE之间的相关性表明，BDE是DPPH（）抗氧化活性的良好预测指标，这表明我们的设计标准是有用的，并且这些化合物应在细胞培养物和动物模型中进行进一步测试。
