Study of Biological Activity of Vitamin E Using Fluorine as Probe.

我们合成了含有一个三氟甲基的a-生育酚，并利用氟核磁共振弛豫时间研究了它们在脂质体中的行为和取向。在这种情况下，比较了两个三氟甲基的两个实验结果，一个在侧链上，另一个在a-生育酚的芳香环上。因此，必须消除脂质体形成和核磁共振测量产生的误差。我们认为，如果使用一种生育酚和两个三氟甲基，就可以避免大多数实验错误。在本研究中，我们计划合成具有两个三氟甲基的a-生育酚，一个在侧链上，另一个在铬醇部分，并成功合成了九种可能的异构体。利用这些生育酚对维生素E的行为和取向进行的研究表明，铬醇环上的一个三氟甲基比侧链上的一个更不容易移动。这表明维生素E的铬醇部分定向于膜表面，并通过铬醇羟基与膜近表面亲水性部分之间的氢键固定在那里，而侧链则定向于膜的内部。分子间的作用力只有范德华引力，所以侧链上的三氟甲基更容易移动。此外，我们还合成了离羧基近或远的氟化脂肪酸。当这些羧酸与脂质体结合时，靠近羧基的氟比远离羧基的氟更不易移动。有趣的是，当a-生育酚被添加到这些脂质体中时，前氟的可移动性降低了。这意味着维生素E增加了膜的机械稳定性。换句话说，维生素E稳定生物膜不仅是一种抗氧化剂，也是一种机械稳定剂。

We had synthesized a-tocopherols having one trifluoromethyl group, and studied their behavior and orientation in liposomes using relaxation time on fluorine-NMR.In this case, the results of two experiments for the two trifluoromethyl groups, one on the side-chain and the other on the aromatic ring of a-tocopherol, were compared. Therefore, it was inevitable to eliminate the errors originated in formation of liposomes and measurement of NMR.We thought that most of these experimental errors would be avoided, if one tocopherols with two trifluoromethyl groups were used.In this study, we planned the synthesis of a-tocopherols having two trifluoromethyl groups, one on the side-chain and the other on the chromanol part, and have succeeded in the syntheses of nine possible isomers.Studies of behavior and orientation of vitamin E using these tocopherols showed that a trifluoromethyl group on the chromanol ring is less movable than one on the side-chain. This shows that the chromanol part of vitamin E is oriented to the surface of the membrane and fixed there by the hydrogen bond between the hydroxyl group of the chromanol and hydrophilic part of the membrane near surface, while the side chain is lriented to an inner part of the membrane. Intermolecular force is only van der Waals attraction, so the trifluoromethyl group on the side-chain is more movable.Further, we have synthesized fatty acids fluorinated near to or far from the carboxyl group. When these carboxylic acid were incorporated to liposome, the fluorine near the carboxyl group were much less movable than one far from the carboxyl group. Interestingly, when a-tocopherol was added to these liposomes, the movability of the former fluorine was lessened. This means that vitamin E increases the mechanical stability of the membrane. In other words, vitamin E stabilizes biological membranes not only as an anti-oxidant, but as a mechanical stabilizer.