Thiophene‐π‐Cyanoacetamides Show Intense and Tau‐selective Turn‐on Fluorescence in the Near‐Infrared Region

Abstract

Investigations into tau‐targeting diagnosis of Alzheimer's disease are currently underway, and the development of tau‐selective molecular probes is urgently required. In this study, the donor‐π‐acceptor architecture of the previously reported tau‐selective fluorescence probe was modified into thiophene‐π‐cyanoacetamides. While the fluorescence properties of the prepared probes were not influenced by the thiophene substituents, intense and tau‐selective turn‐on fluorescence in the near infrared region was observed only in the probes with unsubstituted phenyl or p‐methylphenyl cyanoacetamides in the acceptor functionality. Compared with the parent compound, the newly identified probes showed 1.5 ∼ 4.1 times increase in tau‐selectivity over Aβ fibrils and 3.5 ∼ 4.7 times increase in fluorescence intensity. The tau‐selective fluorescence properties of the title probes were further demonstrated in the cellular milieu, and the green and red fluorescence emitted by GFP and tau‐bound probes, respectively, were shown to be nicely colocalized in the SH‐SY5Y cells stably expressing GFP‐tagged tau.