Abstract This study herein presents the rational design and synthesis of a series of meso ‐CF 3 ‐substituted BODIPY dyes to achieve controllable molecular aggregation and enhanced near‐infrared (NIR) phototherapeutic performance. By constructing a D‐A‐D architecture and introducing furan/thiophene groups, the resulting BODIPYs ( OBB , OHB , SBB and SHB ) form distinct intermolecular aggregates. Single‐crystal X‐ray diffraction analyses reveal that specific hydrogen‐bonding interactions (C‐H⋯F), with precise distances ranging from 2.336 Å to 2.542 Å, induce self‐assembly to form hydrogen‐bonded‐mediated J aggregates. This controlled aggregation induces significant bathochromic shifts, extending absorption into the NIR‐I and NIR‐II regions (up to 937 nm in film), and generates broad absorption bands beneficial for laser matching. Among the self‐assembled nanoparticles (NPs), OBB NPs demonstrate superior properties, including a high photothermal conversion efficiency of 49.7%, a large Stokes shift (87 nm) in water, and type‐I reactive oxygen species generation. In vitro studies against ovarian cancer cells confirm that OBB NPs exhibit low dark toxicity but potent photo‐triggered cytotoxicity, effectively inducing cell apoptosis and necrosis through an ROS‐mediated mechanism. This work underscores the critical role of intermolecular hydrogen bonding in manipulating aggregation‐induced optical properties and provides a fundamental strategy for developing highly effective organic phototherapeutic agents.
Gou et al. (Wed,) studied this question.