Molecular engineering of BODIPY-bridged fluorescent probes for lysosome imaging - a computational study

Lysosome imaging plays an important role in diagnosing many diseases and understanding various intracellular processes. Recently, B0 was reported as a fluorescent probe capable of detecting lysosomal viscosity changes. BODIPY is fused into the molecule as a bridge between the acceptor and donor components of B0, yielding nine new B molecules. Computational design and analysis of their optoelectronic properties were conducted to evaluate their effectiveness as fluorescent probes for lysosome imaging, with a specific target of HSA inside lysosomes. Optimized geometries reveal excellent π electron delocalization, resulting in nearly planar molecular structures. Frontier molecular orbital analysis suggests intramolecular charge transfer, along with π-π* transitions, from donor to bridge. TD-DFT calculations were performed to study absorption properties in the solvent phase, with B3PW91 showing good agreement with experiments. Molecular docking studies indicate that B derivatives can bind with HSA, and molecular dynamics simulations confirm their HSA targeting ability. This investigation highlights the introduction of BODIPY as a bridge for developing new probes capable of producing NIR fluorescence for bio-imaging, aiding in disease diagnosis.