Near‐Infrared Bodipy‐Based Molecular Rotors for β‐Amyloid Imaging In Vivo

Abstract

Abstractβ‐amyloid (Aβ) is one of the important biomarkers for diagnosing Alzheimer's disease (AD). Many near‐infrared probes based on the donor‐π‐acceptor structure have been developed to detect Aβ. Most reported Aβ probes are based on the N,N‐dimethylamino group as the ideal donor, which is a widely accepted binding unit. As such, the development of fluorescent probes with improved binding units to detect Aβ is urgently required. Therefore, with this research three anchoring molecular rotor electron donors consisting of cyclic amines of different ring sizes are developed, namely five‐membered ring (TPyr), six‐membered ring (TPip), and seven‐membered ring (THAI). These new anchored molecular rotors are connected to a 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) and named TPyrBDP, TPipBDP, and THAIBDP. These probes exhibit high affinities (from 28 to 54 nm) for Aβ1–42 aggregates. The six‐membered ring dye TPipBDP exhibits the highest signal‐to‐noise (75.5‐fold) and higher affinity (28.30 ± 5.94 nm). TPipBDP can cross the blood‐brain barrier and exhibits higher fluorescence enhancement with APP/PS1 (AD) double transgenic (Tg) mice than with wild‐type (WT) mice.