Intra- and Intermolecular Synergistic Engineering of Aggregation-Induced Emission Luminogens to Boost Three-Photon Absorption for Through-Skull Brain Imaging

Three-photon
fluorescence microscopic (3PFM) bioimaging is a promising
imaging technique for visualizing the brain in its native environment
thanks to its advantages of high spatial resolution and large imaging
depth. However, developing fluorophores with strong three-photon absorption
(3PA) and bright emission that meets the requirements for efficient
three-photon fluorescence microscopic (3PFM) bioimaging is still challenging.
Herein, four bright fluorophores with aggregation-induced emission
features are facilely synthesized, and their powders exhibit high
quantum yields of up to 56.4%. The intramolecular engineering of luminogens
endows (E)-2-(benzo­[d]­thiazol-2-yl)-3-(7-(diphenylamino)-9-ethyl-9H-carbazol-2-yl)­acrylonitrile (DCBT) molecules with bright
near-infrared emission and large 3PA cross sections of up to 1.57
× 10–78 cm6 s2 photon–2 at 1550 nm, which is boosted by 3.6-fold to 5.61
× 10–78 cm6 s2 photon–2 in DCBT dots benefiting from the extensive intermolecular
interactions in molecular stacking. DCBT dots are successfully applied
for 3PFM imaging of brain vasculature on mice with a removed or intact
skull, providing images with high spatial resolution, and even small
capillaries can be recognized below the skull. This study will inspire
more insights for developing advanced multiphoton absorbing materials
for biomedical applications.