Antioxidants are very crucial in maintaining the normal function of body cells, as they scavenge excess free radical in the body. A set of hydrazone antioxidants was designed by in silico screening. The density functional theory (DFT) method was employed to explore the reaction energetics of their free radical-scavenging mechanism. With the aid of the developed quantitative structure-activity relationship (QSAR) model for hydrazone antioxidants, the structure and antioxidant activity of these compounds were predicted. Three potential reaction mechanisms were investigated, namely, hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). Bond dissociation enthalpy (BDE), adiabatic ionization potential (AIP), proton dissociation enthalpy (PDE), proton affinity (PA), electron transfer enthalpy (ETE) and Gibbs free energy that characterize the various steps in these mechanisms were calculated in the gas phase. A total of 25 hydrazone antioxidants were designed, in which the molecule MHD 017 gave the best antioxidant activity. Among the tested molecules, MHD 017 at the 10-OH site gave the best results for the various thermodynamic parameters calculated. The reaction Gibbs free energy results also indicate that this is the most favoured site for free radical scavenge. The obtained results show that HAT and SPLET mechanisms are the thermodynamically plausible reaction pathways of free radical scavenge by hydrazone antioxidants. The reactivity of these compounds towards the hydroperoxyl radical (HOO·) was greater than that towards the methyl peroxyl radical (CH3OO·) based on the exergonicity of the calculated reaction Gibbs free energy.

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腙抗氧化剂的计算机设计及其自由基清除机制的热力学研究

抗氧化剂对于维持身体细胞的正常功能非常重要，因为它们可以清除体内多余的自由基。通过计算机筛选设计了一组腙抗氧化剂。采用密度泛函理论（DFT）方法探索其自由基清除机制的反应能量学。借助已开发的腙抗氧化剂的定量构效关系 (QSAR) 模型，预测了这些化合物的结构和抗氧化活性。研究了三种潜在的反应机制，即氢原子转移 (HAT)、单电子转移随后质子转移 (SET-PT) 和顺序质子丢失电子转移 (SPLET)。键解离焓 (BDE)、绝热电离势 (AIP)、质子解离焓 (PDE)、在气相中计算表征这些机制中各个步骤的质子亲和力 (PA)、电子转移焓 (ETE) 和吉布斯自由能。总共设计了 25 种腙抗氧化剂，其中分子 MHD 017 具有最佳的抗氧化活性。在测试的分子中，10-OH 位点的 MHD 017 对计算的各种热力学参数给出了最佳结果。反应吉布斯自由能结果也表明这是最受自​​由基清除青睐的位点。所得结果表明，HAT 和 SPLET 机制是腙抗氧化剂清除自由基的热力学合理反应途径。