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

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.