Molecular Crystal Engineering of Organic Chromophores for NIR-II Fluorescence Quantification of Cerebrovascular Function

Although
molecular design strategies for highly bright near-infrared
II (NIR-II) fluorophores were proposed, the lack of solid structural
identification (single crystal) hinders the further development of
this field. This thorny issue is addressed by performing the structure–function
relationship of NIR-II dyes, as confirmed by molecular single crystal
engineering. Single crystal structure analysis confirms that twisted
architectures (large dihedral angles ∼70°) and loose packing
patterns (intermolecular distance of ∼3.4–4.5 Å)
are key elements to enhance the absolute quantum yield (QY) in the
solid state. Through regulating donor–acceptor distance and
donor–acceptor interactions, the resultant well-defined TBP-b-DFA fluorophore displays an absolute QY of 0.4% with an
emission extending to 1400 nm, which is favorable for NIR-II bioimaging.
The cerebrovascular function, including cerebral blood flow and cerebrovascular
reactivity of different conditions, is accurately quantified by a
NIR-II fluorescence wide-field microscope. Our study provides a sight
for designing NIR-II fluorophores, which is useful for studying cerebrovascular
function.