Hierarchically Molecular Programming of Antiparallel H‑Aggregates for NIR Type I Photochemistry

ABSTRACT Developing near‐infrared (NIR) photosensitizers with effective type I reactive oxygen species (ROS) generation remains challenging. H‑aggregates promote triplet formation and charge transfer, but often suffer from substantial absorption blueshifts and excessive thermal deactivation that compromise photosensitization efficacy. Herein, a hierarchically molecular programming strategy is proposed to construct minimal‐blueshift H‐aggregates as robust NIR type I photosensitizers. Primary engineering via π‐bridge extension and acceptor strengthening within a twisted–planar donor–π–acceptor scaffold endows the antiparallel H‐packed TNCF3‐C6‐C2 aggregates with strong NIR absorption (749 nm) and predominant type I ROS generation. Secondary side‐chain programming further regulates the H‐packing and intermolecular electronic interactions to enhance type I ROS generation. Structural, photochemical and theoretical investigations revealed that the branched side chains promote molecular planarization and robust H‑packing, thereby enhancing intersystem crossing and intermolecular charge transfer. The optimized TNCF3‐2C6 with symmetric branched side chain exhibited minimal absorption blueshift (20 nm) upon H‐aggregation, enhanced NIR harvesting ability and a further ∼2‐fold enhancement in ROS generation over the initial TNCF3‐C6‐C2 H‐aggregates, thereby delivering potent tumor inhibition both in vitro and in vivo. Built upon the hierarchical programming of H‐aggregates, this work establishes a supramolecular design paradigm toward modulating excitonic coupling and excited‐state dynamics for high‐performance photo‐functional materials.