Department of Chemistry, Faculty of Science Sivas Cumhuriyet University, 58140, Sivas, Turkey.
J Mol Model. 2024 Nov 15;30(12):401. doi: 10.1007/s00894-024-06196-5.
This study investigates the antioxidant potential of alkyl gallates (C1-C10), focusing on the impact of alkyl chain length and solvent polarity on their antioxidant properties. Known for their biomedical relevance in mitigating oxidative stress, alkyl gallates' structure-activity relationships, particularly regarding chain length and environmental factors, still need to be explored. Key thermochemical parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton affinity (PA), and electron transfer enthalpy (ETE), reveal that shorter alkyl chains (C1-C4) exhibit superior antioxidant activity. In contrast, longer chains (C5-C10) show reduced effectiveness due to steric hindrance and lower solubility in polar solvents. Molecular docking studies also demonstrated favorable binding interactions with vital biological targets, further reinforcing their antioxidant potential.
Quantum chemical calculations were performed using Gaussian 16 with the B3LYP/6-311G(dp) basis set for geometry optimizations. Solvent effects were modeled using the integral equation formalism-polarized continuum model (IEF-PCM). Molecular docking studies were conducted using AutoDockTools 4.2, targeting Tyrosine Kinase Hck, Heme Oxygenase, and Human Serum Albumin to evaluate fundamental binding interactions. These computational methods provided insights into alkyl gallates' chemical reactivity and antioxidant efficiency, allowing for the rational design of more potent antioxidant compounds.
本研究调查了烷（基）没食子酸盐（C1-C10）的抗氧化潜力，重点研究了烷链长度和溶剂极性对其抗氧化性能的影响。烷（基）没食子酸盐在减轻氧化应激方面具有重要的生物医学意义，其结构-活性关系，特别是关于链长和环境因素的关系，仍需要进一步探讨。关键热化学参数，包括键离解焓（BDE）、电离势（IP）、质子亲和力（PA）和电子转移焓（ETE）表明，较短的烷链（C1-C4）表现出更好的抗氧化活性。相比之下，较长的链（C5-C10）由于空间位阻和在极性溶剂中的溶解度降低而表现出较低的效果。分子对接研究也表明与重要的生物靶标具有有利的结合相互作用，进一步增强了它们的抗氧化潜力。
使用 Gaussian 16 软件，采用 B3LYP/6-311G(dp)基组进行几何优化，进行量子化学计算。采用积分方程形式极化连续模型（IEF-PCM）模拟溶剂效应。使用 AutoDockTools 4.2 进行分子对接研究，以酪氨酸激酶 Hck、血红素加氧酶和人血清白蛋白为靶点，评估基本的结合相互作用。这些计算方法提供了对烷（基）没食子酸盐化学反应性和抗氧化效率的深入了解，为更有效的抗氧化化合物的合理设计提供了依据。
