Rath Madhab C, Keny Sageeta J, Upadhyaya Hari P, Adhikari Soumyakanti
Radiation & Photochemistry Division, Mumbai, 400 094, India.
Homi Bhabha National Institute, Mumbai, 400 094, India.
Radiat Phys Chem Oxf Engl 1993. 2023 May;206:110785. doi: 10.1016/j.radphyschem.2023.110785. Epub 2023 Jan 14.
Hydroxychloroquine (HCQ) is a potential drug molecule for treating malaria. Recently it has also been tried as adjustment in Covid 19 therapy. Interaction of HCQ with free radicals is very important, which controls its stability in the environment where free radicals are generated unintentionally. In this report, we present detailed investigation on the reactions of hydrated electrons (e ) and hydroxyl radical (OH) with HCQ in aqueous solution through electron pulse radiolysis technique and computational studies. The degradation of HCQ was found to be faster in the case of reaction with OH radicals. However, the degradation could be substantially slowed down in the presence of antioxidants like ascorbic acid and gallic acid. This revealed that the stability of HCQ could be enhanced in an oxidative environment in the presence of these two compounds, which are easily available through food supplements. Various global and local reactivity parameters are also determined to understand the reactivity trend using Hard-Soft Acid-Base (HSAB) principle in the realm of the DFT methods. Computational studies were performed to elucidate the site-specific reactivity trend towards the electrophilic and nucleophilic attack by calculating the condensed Fukui index for various species of HCQ.
羟氯喹啉（HCQ）是一种治疗疟疾的潜在药物分子。最近，它也被尝试用于调整新冠肺炎的治疗。HCQ与自由基的相互作用非常重要，这决定了其在无意中产生自由基的环境中的稳定性。在本报告中，我们通过电子脉冲辐解技术和计算研究，详细研究了水合电子（e）和羟基自由基（OH）与HCQ在水溶液中的反应。发现HCQ与OH自由基反应时的降解速度更快。然而，在抗坏血酸和没食子酸等抗氧化剂存在的情况下，降解速度会大幅减慢。这表明，在这两种可通过食品补充剂轻松获得的化合物存在的氧化环境中，HCQ的稳定性可以得到增强。还使用密度泛函理论（DFT）方法中的硬软酸碱（HSAB）原理确定了各种全局和局部反应性参数，以了解反应性趋势。通过计算HCQ各种物种的凝聚福井指数，进行了计算研究，以阐明亲电和亲核攻击的位点特异性反应性趋势。
