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

beta-amyloid (A beta) is one of the important biomarkers for diagnosing Alzheimer's disease (AD). Many near-infrared probes based on the donor-pi-acceptor structure have been developed to detect A beta. Most reported A beta 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 A beta 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 A beta(1-42) 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.