Mechanism Research on Thieno-Fused Bis-BODIPY Bifunctional Photosensitizers

This study is dedicated to the development of novel boron-dipyrromethene (BODIPY)-based photosensitizers, focusing on investigating the regulatory mechanism of introducing different electron-donating groups at the α-position on the photosensitizing performance of thieno-bis-BODIPY derivatives, aiming to provide a theoretical basis for cancer photodynamic therapy (PDT). Five thieno-bis-BODIPY molecules (FD1-FD5) were constructed by connecting two BODIPY units via a thiophene π-bridge and introducing various substituents at the α-position of their phenyl groups. Systematic theoretical studies revealed that unilaterally substituted molecules exhibit superior photophysical properties compared to their bilaterally substituted counterparts. The key mechanisms involve structural planarization, increased electrostatic potential difference, and the formation of hybrid LE/CT characteristics in the excited state, all of which collectively promote the intersystem crossing (ISC) process. Specifically, the pyrrole-substituted FD4 exhibits the highest ISC efficiency due to its stronger electron-donating ability and greater molecular planarity, and it is predicted to possess a stronger singlet oxygen generation capability than the methoxy-substituted FD2 while maintaining fluorescence emission. In contrast, bilateral substitution leads to structural distortion, which favors fluorescence emission, as seen in FD5 which exhibits the longest absorption wavelength. This research elucidates the key mechanisms for enhancing ISC and photosensitizing performance from the perspectives of electronic structure and excited-state characteristics, providing theoretical guidance for overcoming limitations such as insufficient tissue penetration in traditional BODIPY photosensitizers and clarifying structure–activity relationships.