Unveiling the Light Induced Energy Transfer Events in Water Soluble Benzothiazole Appended Borondipyrromethene: Synthesis, Photophysical Study, and Applications to Amyloid Binding.

Abstract

Photo-induced energy transfer (PEnT) is a non-invasive photophysical phenomenon by which an excited state energy donor decays to the ground state by transferring the energy to the acceptor, without generating any radical ion-pairs, which is quite desirable for designing molecular probes for biological applications. For the first time, a water soluble benzothiazole (BTZ)-borondipyrromethene (BODIPY) dyad, BTZ-BODIPY-DA, displaying PEnT was synthesized, and used for detecting Aβ₄₀ fibrils. Steady-state and time-resolved fluorescence studies in polar organic solvents and also in PBS, involving the photoexcitation of the BTZ moiety of the dyad, revealed the occurrence of PEnT from ¹BTZ^* to BODIPY. Upon binding with amyloid Aβ₄₀ fibrils, a two-fold enhancement in the fluorescence intensity and enhanced ¹BODIPY* lifetime was observed. Binding of the dyad with Aβ₄₀ peptide and fibrils was explained using molecular dynamics simulations, which further supported that structural rigidification of the bound dyad is responsible for enhanced PEnT. Furthermore, the impact of amyloid binding on the kinetics of PEnT in the dyad was investigated using femtosecond transient absorption studies, and energy transfer rate, k_EnT, of ∼10¹² s^-1 in the amyloid-bound dyad was measured, highlighting the potential use of the dyad as a non-intrusive PEnT operating fluorescent probe for detecting amyloid fibrils.