Tailoring the Dynamics of Excited-State Charge Transfer through Conformational Engineering to Improve Second Near-Infrared Fluorescence for High-Resolution Osteosarcoma Imaging

The dynamics of excited-state charge transfer (CT) in second near-infrared (NIR-II) fluorophore proceeds with conformational change that govern fluorescence. Unveiling the relationship between CT dynamics and conformational change in excited state is of great fundamental significance in optimizing NIR-II fluorescence but remains less explored. This study unveils the pivotal role of large conformational change in promoting the evolution of emissive CT state into nonemissive CT state in NIR-II fluorophore (CA-BBT). Spectroscopic and computational results reveal that large conformational rotation/twisting leads to a pronounced increase in the CT character in excited state. This heightened CT character in CA-BBT enables a rapid evolution of emissive CT state into a nonemissive CT state within 1.4 ps, as observed by ultrafast spectroscopy. Subsequently, this nonemissive state dominates nonradiative decay, resulting in very low NIR-II fluorescence. Preventing such detrimental evolution by constraining the conformational dynamics of CA-BBT results in a 10-fold enhancement of NIR-II fluorescence, enabling high-resolution dynamic visualization of vasculature within osteosarcoma. This study offers a profound understanding of the relationship between CT dynamics and conformational changes in NIR-II fluorescence, presenting innovative perspectives to develop bright NIR-II fluorophores.