Water-Soluble Donor–Acceptor–Donor-Based Fluorophore for High-Resolution NIR-II Fluorescence Imaging Applications

Abstract

Understanding the mechanism of the donor–acceptor–donor (D-A-D) structure on fluorescence properties is very helpful for the design of small molecular NIR-II fluorophores. Based on this D-A-D scaffold, many electron-withdrawing or electron-donating groups and π-bridging moieties have been screened and used to adjust the highest occupied molecular orbital and lowest unoccupied molecular orbital levels to induce fluorescence emission into the NIR-II window. In this work, a series of D-A-D-type NIR-II fluorophores with acceptors of thienoisoindigo (TIIG) or 6,7-bis(4-(hexyloxy)phenyl)-4,9-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4- g ]quinoxaline (TTQ) as well as four typical electron donors of thiophene (T), triphenylamine (TPA), 9,9-dioctyl-9 H -fluorene (F), or 2-(9,9-dioctyl-9H-fluoren-2-yl)thiophene (TF) were synthesized. Their electronic structures and optical properties were investigated via theoretical and experimental studies. It was found that both acceptors and donors significantly influence the fluorescence properties, and TTQ-F exhibits the strongest fluorescence intensity and highest quantum yield. To achieve further NIR-II bioimaging applications, the TTQ-F with desirable NIR-II emission was further modified by PEG 5k to improve its water solubility, and a PEGylated NIR-II polymer, TTQ-F-PEG, was obtained. The bright fluorescence image, good photostability, and large penetration depths of TTQ-F-PEG enabled it to be applied in bioimaging with high resolution and imaging quality. The in vivo NIR-II imaging of vasculature, lymph node, vascular hemorrhage, and gastrointestinal tract in mice was extremely clear. As another application example, TTQ-F-PEG also significantly improved the enhancement of latent fingerprints with good definition and stability.