Extending the Stokes Shifts of Donor–Acceptor Fluorophores by Regulating the Donor Configuration for In Vivo Three-Photon Fluorescence Imaging

Abstract

Simple donor−acceptor (D−A) molecules with large Stokes-shifted and bright near-infrared (NIR) emissions are extremely attractive for the high-resolution three-photon fluorescence (3PF) imaging of deep tissues. Herein, we present a new strategy for significantly extending the Stokes shifts of D−A fluorophores, relying on increasing the excited-state structural/electronic relaxation of the donor moiety. The prototype of the D−A structure DPCN, containing the planar donor N,N′diphenyl-dihydrophenazine (DHP) and the acceptor malononitrile, exhibits normal Stokes-shifted (∼60 nm) NIR emission. By introducing two methyl groups at the ortho sites of the fused DHP ring of DPCN, DMPCN (methyl-decorated DPCN) is developed with an obviously bent donor unit. Compared to DPCN, DMPCN exhibits significantly blueshifted absorption and keeps NIR luminescence with a large Stokes shift of ∼200 nm, mainly due to the remarkable bent-to-planar transformation of the donor upon photoexcitation. Additionally, the DMPCN NPs offer enhanced luminescence quantum yields (11%) and three-photon excitation cross sections. More importantly, DMPCN NPs exhibit excellent performances for in vivo 3PF imaging of the cerebrovascular tissue and lipid droplets (LDs) in a fatty liver with a depth of 1200 and 50 μm, respectively. This research provides a distinct strategy for extending the Stokes shifts of D−A fluorophores, inspiring the utilization of dynamic NIR fluorophores for in vivo 3PF imaging.

An AIE-active type I photosensitizer based on N,N′-diphenyl-dihydrophenazine for high-performance photodynamic therapy under hypoxia

“…The synthesis of the compounds N,N ′-diphenyl-5,10-dihydrophenazine-1-carbaldehyde ( DP-CHO ), and 6,9-dimethyl-5,10-diphenyl-5,10-dihydrophenazine-2-carbaldehyde ( DMP-CHO ) was based on the procedure reported in the literature. 35 DPpy and DMPpy were synthesized by the Knoevenagel reaction of DP-CHO , DMP-CHO , and 1,4-dimethylpyridin-1-ium iodide, respectively. Similarly, DMPSI was obtained by the reaction of DMP-CHO and indole sulfonate.…”

“…The possible reason was that the bending angle Y increases with the introduction of orthomethyl groups, which reduced the conjugation of the DHP skeleton and affected the absorption wavelength of the compound. 34,35 DMPSI's maximum absorption and emission peak wavelengths were longer than those of DMPpy due to the stronger electron acceptor indole sulfonate. However, the Stokes shifts of DMPpy (B270 nm) were much larger than that of DPpy and DMPSI.…”

“…[30][31][32][33] Recently, our group has reported a series of N,N 0 -diphenyldihydrophenazine (DHP)-based fluorophores and approved that increasing the steric hindrance of the DHP molecule further broadens the Stokes shifts. 34,35 Meanwhile, fused structure and rotatable benzene ring give it potential for AIEenhanced emission. 36 Inspired by the above-mentioned factors, we fabricated two D-A fluorophores with near-infrared (NIR) emission from distinct building modules: (1) the reductant moieties DHP and its ortho-dimethyl-substituted derivative (DMP) to serve as strong electron donors; (2) styrenic pyridinium cation as an acceptor to ensure firm ICT intensity for the excited triplet energy conversion; (3) iodide anion and synergistic donors with strong reducibility to create electron-rich conditions and provide electrons to the excited PSs.…”

Aggregation-Induced Emission (AIE), Life and Health

“…This photophysical behavior has been termed aggregation-induced emission (AIE). After more than 20 years of development in the field of AIE, the working mechanism of restriction of intramolecular motion (RIM) has been established and well-recognized. , RIM can lead to conformational rigidification, thereby suppressing nonradiative decay pathways, e.g., vibronic coupling, conical intersection, and photochemical reactions, thus contributing to the enhanced luminescence process. − The discovery and exploration of AIE has also greatly advanced the field of precision medicine and light-based healthcare. , For fluorescence imaging, AIE luminogens (AIEgens) and their formed NPs are endowed with the inherent advantages of low background noise, fair photostability, − large Stokes shift, − biocompatibility, − high brightness, ,− and deeper tissue penetration and higher spatial resolution. , In particular, the tetraphenylethylene (TPE) skeleton is the most versatile AIEgene because it can be designed to have various desired functions by introducing functional groups or π-extensions …”

Design, synthesis and functionalization of BODIPY dyes: applications in dye-sensitized solar cells (DSSCs) and photodynamic therapy (PDT)

“…15,16 The D-A strength, which is dependent on the type of donor group, acceptor group as well as the type of p-linker/spacer unit, plays a significant role in the development of D-A systems. 17 D-A chromophores with a low bandgap exhibit potential applications in DSSCs, 18 bulk heterojunction organic solar cells (BHJOSCs), 19 NLOs, 20 organic field effect transistors (OFETs), 21 bioimaging 22 and photodynamic therapy. 23 1.1.…”