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α-生育酚，并利用氟核磁共振的驰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实验结果，一个位于α-生育酚的侧链上，另一个位于α-生育酚的芳环上。因此，消除脂质体形成和测定核磁共振的误差是不可避免的。我们认为，如果使用一个带有两个三氟甲基的生育酚，大部分实验误差将被避免。在本研究中，我们计划合成具有两个三氟甲基的α-生育酚，一个在侧链上，另一个在色满酚部分，并成功地合成了九种可能的异构体。这表明维生素E中的色素部分定位于膜表面，并通过色素羟基与膜亲水部分之间的氢键固定在膜的近表面，而侧链则指向膜的内部。分子间作用力只是范德华引力，所以侧链上的三氟甲基更易移动。此外，我们还合成了靠近或远离羧基的含氟脂肪酸。当这些羧酸被引入脂质体时，靠近羧基的氟比远离羧基的氟的可移动性要小得多。有趣的是，当α-生育酚被添加到这些脂质体中时，原来的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不仅可以作为抗氧化剂稳定生物膜，还可以作为机械稳定剂。

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.