合成手性氮氧自由基标记的布洛芬及其与脂质膜的相互作用。

Synthesis of Spin-Labeled Ibuprofen and Its Interaction with Lipid Membranes.

机构信息

V.V. Voevodsky Institute of Chemical Kinetics and Combustion, SB RAS, 630090 Novosibirsk, Russia.

Department of Physics, Novosibirsk State University, 630090 Novosibirsk, Russia.

出版信息

Molecules. 2022 Jun 27;27(13):4127. doi: 10.3390/molecules27134127.

DOI:10.3390/molecules27134127

PMID:35807376

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9268589/

Abstract

Ibuprofen is a non-steroidal anti-inflammatory drug possessing analgesic and antipyretic activity. Electron paramagnetic resonance (EPR) spectroscopy could be applied to study its interaction with biological membranes and proteins if its spin-labeled analogs were synthesized. Here, a simple sequence of ibuprofen transformations-nitration, esterification, reduction, Sandmeyer reaction, Sonogashira cross-coupling, oxidation and saponification-was developed to attain this goal. The synthesis resulted in spin-labeled ibuprofen (ibuprofen-SL) in which the spin label TEMPOL is attached to the benzene ring. EPR spectra confirmed interaction of ibuprofen-SL with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. Using H electron spin echo envelope modulation (ESEEM) spectroscopy, ibuprofen-SL was found to be embedded into the hydrophobic bilayer interior.

摘要

布洛芬是一种具有镇痛和解热作用的非甾体抗炎药。如果合成了其自旋标记类似物，则可以应用电子顺磁共振（EPR）光谱来研究它与生物膜和蛋白质的相互作用。在这里，开发了一个简单的布洛芬转化序列-硝化，酯化，还原，Sandmeyer 反应，Sonogashira 交叉偶联，氧化和皂化-以实现这一目标。该合成得到了自旋标记的布洛芬（布洛芬-SL），其中自旋标记 TEMPOL 连接到苯环上。EPR 光谱证实了布洛芬-SL 与 1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）双层的相互作用。通过使用 H 电子自旋回波包络调制（ESEEM）光谱法，发现布洛芬-SL 嵌入到疏水性双层内部。