Two Key Descriptors for Designing Second Near-Infrared Dyes and Experimental Validation

Second near-infrared (NIR-II) optical imaging technology has emerged as a powerful tool for diagnostic and image-guided surgery due to its higher imaging contrast. However, a general strategy for efficiently designing NIR-II organic molecules is still lacking, because NIR-II dyes are usually difficult to synthesize, which has impeded the rapid development of NIR-II bioprobes. Herein, based on the theoretical calculations on 62 multiaryl-pyrrole (MAP) systems with spectra ranging from the visible to the NIR-II region, a continuous red shift of the spectra toward the NIR-II region could be achieved by adjusting the type and site of substituents on the MAPs. Two descriptors (Δ E gs and μ gs ) were identified as exhibiting strong correlations with the maximum absorption/emission wavelengths, and the descriptors could be used to predict the emission spectrum in the NIR-II region only if Δ E gs ≤ 2.5 eV and μ gs ≤ 22.55 D. The experimental absorption and emission spectra of ten MAPs fully confirmed the theoretical predictions, and biological imaging in vivo of newly designed MAP23-BBT showed high spatial resolution in the NIR-II region in deep tissue angiography. More importantly, both descriptors of Δ E gs and μ gs have shown general applicability to most of the reported donor–acceptor–donor-type non-MAP NIR-II dyes. These results have broad implications for the efficient design of NIR-II dyes.