Construction of Photosensitizer Candidates in Photodynamic Therapy: Computer Aided Design, Calculation, and Screening

Thiophene and pyrrole units are extensively utilized in light-responsive materials and have significantly advanced the field of organic photovoltaics (OPV). This progress has inspired our exploration of photosensitizers (PS) for photodynamic therapy (PDT). Currently, traditional PS face limitations in clinical application, including a restricted variety and narrow applicability. Drawing upon molecular design concepts from OPV, we aim to transcend these limitations in PDT. Given the abundance of candidate molecules, effective screening is crucial. Theoretical calculations and electronic structure analyses serve as precise and practical screening methods. In this study, we adopted strategies successfully employed in OPV molecular design, focusing on donor–acceptor (D-A) and acceptor–donor–acceptor (A-D-A) structures. Using density functional theory (DFT) and time-dependent density functional theory (TDDFT), we systematically designed combinations of promising organic fragments. These fragments include polythiophene and polypyrrole-dominated donor structures, paired with five electron acceptors: indene (Ind), diketopyrrole (DPP), naphthalimide (Ni), benzothiazole (Btd), and dithiazolyl diketopyrrole (Tbo). Through meticulous calculations, we obtained electronic structures and spectral properties for all candidate molecules, facilitating an efficient screening process. Our findings highlight that those combinations of polypyrrole-based frameworks with DPP, Ni, and Btd show significant promise for PS applications. Approximately 13% of candidates were selected through comprehensive comparison, markedly reducing molecular design time and experimental costs. This interdisciplinary approach holds potential to pave the way for more targeted and successful PS designs.