University of Natural Resources and Life Sciences, Vienna, Institute of Chemistry of Renewable Resources, Konrad-Lorenz-Straße 24, 3430, Tulln an der Donau, Austria.
Johan Gadolin Process Chemistry Centre, Åbo Akademi University, Porthansgatan 3, Turku, 20500 Åbo/Turku, Finland.
ChemistryOpen. 2021 Apr;10(4):421-429. doi: 10.1002/open.202000306. Epub 2021 Mar 5.
As a prominent member of the vitamin E group, α-tocopherol is an important lipophilic antioxidant. It has a special oxidation chemistry that involves phenoxyl radicals, quinones and quinone methides. During the oxidation to the ortho-quinone methide, an intermediary zwitterion is formed. This aromatic intermediate turns into the quinone methide by simply rotating the initially oxidized, exocyclic methyl group into the molecule's plane. This initial zwitterionic intermediate and the quinone methide are not resonance structures but individual species, whose distinct electronic structures are separated by a mere 90° bond rotation. In this work, we hindered this crucial rotation, by substituting the affected methyl group with alkyl or phenyl groups. The alkyl groups slowed down the conversion to the quinone methide by 18-times, while the phenyl substituents, which additionally stabilize the zwitterion electronically, completely halted the conversion to the quinone methide at -78 °C, allowing for the first time the direct observation of a tocopherol-derived zwitterion. Employing a C-labeled model, the individual steps of the oxidation sequence could be observed directly by NMR, and the activation energy for the rotation could be estimated to be approximately 2.8 kcal/mol. Reaction rates were solvent dependent, with polar solvents exerting a stabilizing effect on the zwitterion. The observed effects confirmed the central relevance of the rotation step in the change from the aromatic to the quinoid state and allowed a more detailed examination of the oxidation behavior of tocopherol. The concept that a simple bond rotation can be used to switch between an aromatic and an anti-aromatic structure could find its use in molecular switches or molecular engines, driven by the specific absorption of external energy.
作为维生素 E 家族的杰出成员，α-生育酚是一种重要的亲脂性抗氧化剂。它具有特殊的氧化化学性质，涉及酚氧自由基、醌和醌亚甲基。在氧化为邻醌亚甲基的过程中，会形成一个中间两性离子。这种芳香中间体通过简单地将最初氧化的、环外甲基旋转到分子平面内，转化为醌亚甲基。这个初始两性离子中间体和醌亚甲基不是共振结构，而是两种单独的物种，它们的明显电子结构仅通过 90°键旋转来分离。在这项工作中，我们通过用烷基或苯基取代受影响的甲基来阻碍这个关键的旋转。烷基基团使转化为醌亚甲基的速度减慢了 18 倍，而苯基取代基在电子上额外稳定了两性离子，完全阻止了在-78°C 下转化为醌亚甲基，从而首次能够直接观察到生育酚衍生的两性离子。通过使用 C 标记的模型，通过 NMR 可以直接观察氧化序列的各个步骤，并且可以估计旋转的活化能约为 2.8 kcal/mol。反应速率取决于溶剂，极性溶剂对两性离子具有稳定作用。观察到的效应证实了旋转步骤在芳香族到醌型状态的转变中的核心重要性，并允许更详细地研究生育酚的氧化行为。一个简单的键旋转可以用来在芳香族和反芳香族结构之间切换的概念，可以在分子开关或分子发动机中找到应用，这些开关或发动机由外部能量的特定吸收来驱动。
