Organic Molecules for Photothermal Therapy in the Second Near-Infrared Window: Theoretical Exploration of Selenium Atomic Incorporation and Ethynyl-bridged Dual-Acceptor Strategy

The demand for efficient organic small-molecule photothermal agents (OSMPTAs) in the second near-infrared (NIR-II) window is critical for deep-tissue photothermal therapy. Using DFT and TDDFT, we investigated the impact of selenium (Se) incorporation and an ethynyl-bridged dual-acceptor strategy on donor-acceptor-donor systems. Se doping narrows the HOMO-LUMO gap, while the ethynyl bridge extends π-conjugation, synergistically red-shifting absorption up to 1275 nm. Reorganization energy analysis reveals the rigid ethynyl linker mitigates structural repulsion in dual-acceptor systems without sacrificing photothermal performance. Crucially, predicted non-radiative rate constants remain orders of magnitude higher than radiative and intersystem crossing ones, suggesting favorable non-radiative energy dissipation, which is helpful for intense heat generation. These findings establish a clear structure-property relationship, demonstrating that integrating Se doping with ethynyl-bridged dual-acceptors simultaneously achieves superior NIR-II absorption and favorable theoretical photothermal potential, providing a clear rational design for photothermal agents.