Department of Food Science and Technology, National University of Singapore, 2 Science Drive 2, Singapore 117542, Republic of Singapore.
Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore.
J Agric Food Chem. 2022 Jul 20;70(28):8799-8807. doi: 10.1021/acs.jafc.2c03860. Epub 2022 Jul 10.
Flavonoids, a class of polyphenolic substances widely present in the plant realm, are considered as ideal hypochlorite scavengers. However, to our knowledge, little study has focused on the structure-activity relationship between flavonoids and hypochlorite scavenging capacity. Herein, we report for the first time the three-dimensional quantitative structure and activity relationship (3D-QSAR) combined with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Four models derived from CoMFA and CoMSIA with different combinations of descriptors were built and compared; the CoMFA model, which included both steric and electrostatic fields, showed great potential ( = 0.989; = 0.818) in predictive quality according to both internal and external validation criteria. Additionally, the average local ionization energy (ALIE), electrostatic potential (ESP), and orbital weighted dual descriptor (OWDD) were determined to identify the key structural moiety for scavenging capacity of flavonoids against hypochlorite. The computational results indicated that hypochlorous acid (HClO) serves as an electrophile undergoing electrophilic addition to the C6 carbon, which has the highest negative charge density, which are influenced by the functional groups on the flavones. The DFT calculated mechanism revealed the catalytic role of water of mono- and di-chlorination reactions, characterized by low activation barriers, and the involvement of neutral, instead of high-energy carbocation, intermediates.
类黄酮是广泛存在于植物界的一类多酚物质，被认为是理想的次氯酸盐清除剂。然而，据我们所知，很少有研究关注类黄酮与次氯酸盐清除能力之间的构效关系。在此，我们首次报道了三维定量构效关系（3D-QSAR）结合比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）。基于描述符的不同组合，从 CoMFA 和 CoMSIA 中得到了四个模型，并对其进行了比较；CoMFA 模型同时包含了立体和静电场，根据内部和外部验证标准，具有很大的预测潜力（ = 0.989； = 0.818）。此外，还确定了平均局部电离能（ALIE）、静电势（ESP）和轨道加权双描述符（OWDD），以确定清除类黄酮对次氯酸盐的能力的关键结构部分。计算结果表明，次氯酸（HClO）作为亲电试剂，与具有最高负电荷密度的 C6 碳发生亲电加成反应，这受到黄酮类化合物上的官能团的影响。DFT 计算的机制揭示了单氯化和双氯化反应的催化作用，其特点是低活化能垒，以及涉及中性而不是高能碳正离子的中间体。
