Kaur Chhinderpal, Mandal Debasish
Department of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology Patiala-147004 Punjab India
RSC Adv. 2025 Jan 3;15(1):357-369. doi: 10.1039/d4ra07625g. eCollection 2025 Jan 2.
In this study, a detailed DFT investigation was conducted to systematically analyze the scavenging activity of six hydrazone compounds (1-6) against HOO˙ and CHOO˙ radicals. Three mechanistic pathways were explored: hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SETPT), and sequential proton loss electron transfer (SPLET). These mechanisms were evaluated based on thermodynamic parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA), and electron transfer enthalpy (ETE) in the gas phase, water, and pentyl ethanoate. HAT was identified as the most favorable mechanism in the gas phase, while SPLET was preferred in water. Among the studied compounds, compound 2 showed the highest rate constants for HOO˙ scavenging following the HAT mechanism in the gas phase observed at the O2'-H bond with a value of 6.02 × 10 M s. For CHOO˙ scavenging, the same compound exhibited the highest rate constants at the N8-H (9.03 × 10 M s) and O2'-H (7.22 × 10 M s) sites. The calculated overall rate constant values of compound 2 are (HOO˙) = 6.86 × 10 M s and (CHOO˙) = 1.63 × 10 M s. These results suggest that compound 2 exhibits antioxidant activities comparable to butylated hydroxyanisole (BHA), consistent with experimental findings, indicating its potential as an effective scavenger of hydroperoxyl and methoxy peroxyl radicals. In aqueous solution, the anionic form of compound 2 showed the greatest HOO˙ and CHOO˙ radical scavenging activity among all of the studied compounds with rate constants of = 1.8 × 10 M s and = 3.3 × 10 M s, respectively. Compared with some typical antioxidants such as rubiadin, natural fraxin, and natural anthraquinones, compound 2 showed higher HOO˙ and CHOO˙ radical scavenging activity in water. Thus, compound 2 is a promising antioxidant in aqueous physiological environments.
在本研究中，进行了详细的密度泛函理论（DFT）研究，以系统分析六种腙化合物（1-6）对HOO˙和CHOO˙自由基的清除活性。探索了三种反应机理途径：氢原子转移（HAT）、单电子转移后质子转移（SETPT）和连续质子损失电子转移（SPLET）。基于热力学参数对这些机理进行了评估，包括气相、水和乙酸戊酯中的键解离焓（BDE）、电离势（IP）、质子解离焓（PDE）、质子亲和势（PA）和电子转移焓（ETE）。HAT被确定为气相中最有利的机理，而在水中则首选SPLET。在所研究的化合物中，化合物2在气相中通过HAT机理清除HOO˙时，在O2'-H键处表现出最高的速率常数，值为6.02×10 M s。对于CHOO˙清除，同一化合物在N8-H（9.03×10 M s）和O2'-H（7.22×10 M s）位点表现出最高的速率常数。化合物2的计算总速率常数分别为 （HOO˙） = 6.86×10 M s和 （CHOO˙） = 1.63×10 M s。这些结果表明，化合物2表现出与丁基羟基茴香醚（BHA）相当的抗氧化活性，与实验结果一致，表明其作为氢过氧自由基和甲氧基过氧自由基有效清除剂的潜力。在水溶液中，化合物2的阴离子形式在所有研究化合物中表现出最大的HOO˙和CHOO˙自由基清除活性，速率常数分别为 =1.8×10 M s和 =3.3×10 M s。与一些典型的抗氧化剂如红玉红、天然秦皮素和天然蒽醌相比，化合物2在水中表现出更高的HOO˙和CHOO˙自由基清除活性。因此，化合物2在水性生理环境中是一种有前景的抗氧化剂。
