Molecular engineering of BODIPY-bridged fluorescent probes for lysosome imaging – a computational study
Prince Joby, R. Ramasamy, Rajadurai Vijay Solomon, P. Wilson
Abstract
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.