Theoretical Insights into Heteroatom Substitution Engineering for Modulating the Luminescence Performance of NIR-II Fluorophores

Fluorescence imaging in the second near-infrared (NIR-II) region offering high temporal-spatial resolution has been focused in biomedical research and clinical applications. Although various NIR-II fluorophores have been developed, the rational design of novel chromophores remains a major challenge. Herein, based on a molecular skeleton with a benzobisthiadiazole acceptor and diphenylamine donors, three isomers featuring diazine unit as the bridging spacers are theoretically constructed. Photophysical properties reveal that the incorporation of pyrazinyl and pyrimidinyl groups enhances the molecular conjugation and intramolecular charge transfer, thereby enabling long-wavelength absorption and emission characteristics of the fluorophore. Notably, heteroatom replacement at the para-positions on the phenyl moiety induces an optimal luminescence efficiency within the NIR-II region, which can be attributed to the enlarged adiabatic excitation energy and reduced nonadiabatic electron coupling caused by the suppression of in-plane bending vibrations on the diazine unit. As a result, the pyrazinyl-contained fluorophore achieves both efficient NIR-II emission and improved fluorescence brightness, making it a promising candidate as NIR-II fluorophore. These findings highlight the effectiveness of heteroatom substitution strategy for modulating the molecular luminescence performances, providing new insights on the optimized design of advanced NIR-II molecular fluorophores for bioimaging applications.