Fluorine-19 is an ideal nucleus for studying biological systems using NMR due to its rarity in biological environments and its favorable magnetic properties. In this work, we used a mixture of monofluorinated palmitic acids (PAs) as tracers to investigate the molecular interaction of the fluorinated drug rosuvastatin in model lipid membranes. More specifically, PAs labeled at the fourth and eighth carbon positions of their acyl chains were coincorporated in phospholipid bilayers to probe different depths of the hydrophobic core. First, the 19F chemical shift anisotropy (CSA), indicative of membrane fluidity, was simultaneously determined for fatty acids (FAs) and the fluorinated drug using either slow magic-angle spinning (MAS) 1D 19F solid-state NMR (SS-NMR) or MAS 2D 19F-19F SS-NMR with CSA recoupling. Membrane heterogeneity and selective partitioning of rosuvastatin into fluid regions could thus be evidenced. We then examined the possibility of mapping intermolecular distances in bilayers, in both the fluid and gel phases, using 19F-19F and 1H-19F correlation experiments by SS-NMR using MAS. Spatial correlations were evidenced between the two PAs in the gel phase, while contacts between the statin and the lipids were detected in the fluid phase. This work paves the way to mapping membrane-active molecules in intact membranes, and stresses the need for new labeling strategies for this purpose.

中文翻译：

---

通过 19F 固体 NMR 同时评估膜双层结构和药物插入


Fluorine-19 是使用 NMR 研究生物系统的理想核，因为它在生物环境中很稀有，并且具有良好的磁性。在这项工作中，我们使用单氟棕榈酸 （PAs） 的混合物作为示踪剂来研究氟化药物瑞舒伐他汀在模型脂质膜中的分子相互作用。更具体地说，标记在酰基链第四和第八碳位置的 PA 共掺入磷脂双层中，以探测疏水核心的不同深度。首先，使用慢魔角旋转 （MAS） 1D 19F 固态 NMR （SS-NMR） 或 MAS 2D 19F-19F SS-NMR 与 CSA 再耦合，同时测定脂肪酸 （FA） 和氟化药物的 19F 化学位移各向异性 （CSA），指示膜流动性。因此可以证明瑞舒伐他汀的膜异质性和选择性分配为液体区域。然后，我们使用 MAS 通过 SS-NMR 的 19F-19F 和 1H-19F 相关实验，检查了在流体和凝胶相中绘制双层分子间距离的可能性。在凝胶相中，两种 PAs 之间存在空间相关性，而在液相中检测到他汀类药物和脂质之间的接触。这项工作为在完整膜中绘制膜活性分子铺平了道路，并强调了为此目的需要新的标记策略。