Department of Chemistry, North-West University-Mafikeng Campus, Private Bag x 2046, Mmabatho 2735, South Africa.
Chem Res Toxicol. 2012 Oct 15;25(10):2153-66. doi: 10.1021/tx300244z. Epub 2012 Sep 17.
Rooperol is a norlignan derivative with numerous biological activities including immunomodulatory, antitumor, anticonvulsant, antibacterial, and antioxidant activities. Its antioxidant activity has been studied by means of experimental techniques, which have shown that it has the ability to scavenge radical species, inhibit lipid peroxidation, and reduce transition metal ions. However, its ability to scavenge radical species and chelate transition metal ions has not been previously studied by means of quantum chemical methods. In this study, density functional theory (DFT) is utilized to investigate the conformational preferences of rooperol, the ability of rooperol to scavenge radical species, and the rooperol···Cu interaction mechanism, which might assist in understanding the antioxidant and prooxidant activities of rooperol. The study was performed in vacuo and in selected solvents. The results suggest that lowest-energy conformers of neutral rooperol are stabilized by two intramolecular hydrogen bonds, while the radical species of rooperol are stabilized by both intramolecular hydrogen bonds and spin delocalization of the unpaired electron. The results in different solvents show that the stability of the conformers of rooperol increases with the increase in the solvent polarity, while the stability of radical species decreases with increase in solvent polarity. The stability of the rooperol···Cu complexes depends on the site on which the Cu ion binds, while the binding strength depends on both the nature of the cation and the nature of the binding site. The inclusion of solvent effects using the polarizable continuum model shows that the rooperol···Cu interaction energies are highly overestimated in vacuo. Finally, the results suggest that the antioxidant activity shown by rooperol corresponds to its interaction with closed-shell transition metal ions, while its prooxidant activity is a result of its interaction with open-shell transition metal ions.
罗泊洛尔是一种愈创木烷衍生物，具有多种生物活性，包括免疫调节、抗肿瘤、抗惊厥、抗菌和抗氧化活性。其抗氧化活性已通过实验技术进行了研究，结果表明它具有清除自由基、抑制脂质过氧化和减少过渡金属离子的能力。然而，其清除自由基和螯合过渡金属离子的能力尚未通过量子化学方法进行研究。在这项研究中，利用密度泛函理论（DFT）研究了罗泊洛尔的构象偏好、清除自由基的能力以及罗泊洛尔···Cu 相互作用机制，这可能有助于理解罗泊洛尔的抗氧化和促氧化活性。该研究在真空中和选定的溶剂中进行。结果表明，中性罗泊洛尔的最低能量构象由两个分子内氢键稳定，而罗泊洛尔的自由基由分子内氢键和未配对电子的自旋离域稳定。不同溶剂中的结果表明，罗泊洛尔构象的稳定性随溶剂极性的增加而增加，而自由基的稳定性随溶剂极性的增加而降低。罗泊洛尔···Cu 配合物的稳定性取决于 Cu 离子结合的位置，而结合强度取决于阳离子的性质和结合位点的性质。使用极化连续体模型包含溶剂效应表明，在真空中，罗泊洛尔···Cu 相互作用能被高度高估。最后，结果表明，罗泊洛尔表现出的抗氧化活性与其与闭壳过渡金属离子的相互作用相对应，而其促氧化活性则是其与开壳过渡金属离子相互作用的结果。
