Intermolecular hydrogen-bonded associates of BODIPYs drive controllable aggregates and enhanced NIR phototherapeutic performance

Abstract

This study herein presents the rational design and synthesis of a series of meso-CF₃-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.

Keywords

associate / BODIPY / controllable aggregation / intermolecular hydrogen-bond / NIR

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2026 The Author(s). Smart Molecules published by John Wiley & Sons Australia, Ltd on behalf of Dalian University of Technology.