Zhang Jun, Wang Jun, Sandberg Alexander, Wu Xiongyu, Nyström Sofie, LeVine Harry, Konradsson Peter, Hammarström Per, Durbeej Bo, Lindgren Mikael
Division of Chemistry Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.
Division of Theoretical Chemistry Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.
Chemphyschem. 2018 Nov 19;19(22):3001-3009. doi: 10.1002/cphc.201800823. Epub 2018 Oct 8.
Two analogues to the fluorescent amyloid probe 2,5-bis(4'-hydroxy-3'-carboxy-styryl)benzene (X-34) were synthesized based on the trans-stilbene pyrene scaffold (Py1SA and Py2SA). The compounds show strikingly different emission spectra when bound to preformed Aβ1-42 fibrils. This remarkable emission difference is retained when bound to amyloid fibrils of four distinct proteins, suggesting a common binding configuration for each molecule. Density functional theory calculations show that Py1SA is twisted, while Py2SA is more planar. Still, an analysis of the highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs) of the two compounds indicates that the degree of electronic coupling between the pyrene and salicylic acid (SA) moieties is larger in Py1SA than in Py2SA. Excited state intramolecular proton transfer (ESIPT) coupled-charge transfer (ICT) was observed for the anionic form in polar solvents. We conclude that ICT properties of trans-stilbene derivatives can be utilized for amyloid probe design with large changes in emission spectra and decay times from analogous chemical structures depending on the detailed physical nature of the binding site.
基于反式芪芘支架（Py1SA和Py2SA）合成了荧光淀粉样探针2,5-双（4'-羟基-3'-羧基苯乙烯基）苯（X-34）的两种类似物。当与预先形成的Aβ1-42原纤维结合时，这些化合物显示出截然不同的发射光谱。当与四种不同蛋白质的淀粉样原纤维结合时，这种显著的发射差异得以保留，这表明每个分子具有共同的结合构型。密度泛函理论计算表明，Py1SA呈扭曲状，而Py2SA更平面。尽管如此，对这两种化合物的最高占据分子轨道（HOMO）和最低未占据分子轨道（LUMO）的分析表明，芘与水杨酸（SA）部分之间的电子耦合程度在Py1SA中比在Py2SA中更大。在极性溶剂中观察到了阴离子形式的激发态分子内质子转移（ESIPT）耦合电荷转移（ICT）。我们得出结论，反式芪衍生物的ICT特性可用于淀粉样探针设计，根据结合位点的详细物理性质，类似化学结构的发射光谱和衰减时间会发生很大变化。
