A theoretical thermodynamic study was conducted to investigate the antioxidant activity and mechanism of 1,3,4-oxadiazol-2-ylthieno[2,3-d]pyrimidin-4-amine derivatives (OTP) using a Density Functional Theory (DFT) approach. The study assessed how solvent environments influence the antioxidant properties of these derivatives. With the increasing prevalence of diseases linked to oxidative stress, such as cancer and cardiovascular diseases, antioxidants are crucial in mitigating the damage caused by free radicals. Previous research has demonstrated the remarkable scavenging abilities of 1,3,4-oxadiazole derivatives, prompting this investigation into their potential using computational methods. DFT calculations were employed to analyze key parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), and electron transfer enthalpy (ETE), to delineate the antioxidant mechanisms of these compounds. Our findings indicate that specific electron-donating groups such as amine on the phenyl rings significantly enhance the antioxidant activities of these derivatives. The study also integrates global and local reactivity descriptors, such as Fukui functions and HOMO-LUMO energies, to predict the stability and reactivity of these molecules, providing insights into their potential as effective synthetic antioxidants in pharmaceutical applications.

中文翻译：

---

1,3,4-恶二唑-2-基噻吩并[2,3-d]嘧啶-4-胺衍生物的抗氧化机制和构效关系的理论研究：一种计算方法


采用密度泛函理论 (DFT) 方法进行理论热力学研究，研究 1,3,4-恶二唑-2-基噻吩并[2,3-d]嘧啶-4-胺衍生物 (OTP) 的抗氧化活性和机制。该研究评估了溶剂环境如何影响这些衍生物的抗氧化特性。随着与氧化应激相关的疾病（例如癌症和心血管疾病）的日益流行，抗氧化剂对于减轻自由基造成的损害至关重要。先前的研究已经证明了 1,3,4-恶二唑衍生物具有显着的清除能力，促使我们利用计算方法对其潜力进行研究。采用DFT计算来分析关键参数，包括键解离焓（BDE）、电离势（IP）、质子解离焓（PDE）和电子转移焓（ETE），以描述这些化合物的抗氧化机制。我们的研究结果表明，特定的给电子基团（例如苯环上的胺）显着增强了这些衍生物的抗氧化活性。该研究还整合了全局和局部反应性描述符，例如 Fukui 函数和 HOMO-LUMO 能量，以预测这些分子的稳定性和反应性，从而深入了解它们在药物应用中作为有效合成抗氧化剂的潜力。