Effect of Iodine, and Polar Group Substitutions at α,β,$$ \alpha, \beta, $$ and meso$$ meso $$‐Positions on Some Photophysical Properties of BODIPY‐Based Photosensitizers Relevant to Photodynamic Therapy

ABSTRACTBODIPY‐based photosensitizers are well‐known for their two‐photon (TP) activity. The BODIPY core can be substituted at three distinct positions: , , and . Current literature suggests that substitutions at the position are the most commonly preferred due to their labile nature, which makes synthesis easier. However, there has been no systematic study investigating how the position of substitutions impacts the TP activity of BODIPY systems. Furthermore, we found no reports addressing the effects of heavy atoms, such as iodine, on this property. To fill these gaps, this work presents a systematic investigation of how substitution of iodine at the position, along with a few polar groups at other positions in the BODIPY core, affects the TP activity. For this purpose, 36 BODIPY systems were designed and their one‐ and two‐photon (TP) activities were studied computationally using the state‐of‐the‐art resolution‐of‐identity coupled cluster with doubles method. To explain the effect of iodine, and that of nature and position of polar groups in the BODIPY core on TP activity, we used a three‐state model. Further, we also performed molecular docking and molecular dynamics simulations to study the interaction of the designed molecules with the Human Serum Albumin (HSA) protein. Our findings suggest that substituting iodine at the position increases the TP activity. Additionally, we observed that the substitution of polar groups at the position results in larger TP activity compared to and positions. Molecular docking and simulation results revealed that the designed molecules interact with HSA, and the complexes formed are stable throughout the simulation period.