Near-infrared (NIR) fluorophores absorbing maximally
in the region
beyond 800 nm, i.e., deep-NIR spectral region, are actively sought
for biomedical applications. Ideal dyes are bright, nontoxic, photostable,
biocompatible, and easily derivatized to introduce functionalities
(e.g., for bioconjugation or aqueous solubility). The rational design
of such fluorophores remains a major challenge. Silicon-substituted
rhodamines have been successful for bioimaging applications in the
red spectral region. The longer-wavelength silicon-substituted congeners
for the deep-NIR spectral region are unknown to date. We successfully
prepared four silicon-substituted bis-benzannulated rhodamine dyes
(ESi5a–ESi5d), with an efficient five-step cascade
on a gram-scale. Because of the extensive overlapping of their HOMO–LUMO
orbitals, ESi5a–ESi5d are highly absorbing (λabs ≈ 865 nm and ε > 105 cm–1 M–1). By restraining both the rotational
freedom
via annulation and the vibrational freedom via silicon-imparted strain,
the fluorochromic scaffold of ESi5 is highly rigid, resulting
in an unusually long fluorescence lifetime (τ > 700 ps in
CH2Cl2) and a high fluorescence quantum yield
(ϕ
= 0.14 in CH2Cl2). Their half-lives toward photobleaching
are 2 orders of magnitude longer than the current standard (ICG in
serum). They are stable in the presence of biorelevant concentration
of nucleophiles or reactive oxygen species. They are minimally toxic
and readily metabolized. Upon tail vein injection of ESi5a (as an example), the vasculature of a nude mouse was imaged with
a high signal-to-background ratio. ESi5 dyes have broad
potentials for bioimaging in the deep-NIR spectral region.
Fluorescent emitters with long exciton lifetime and high luminescence efficiency show promising application in organic light emitting diodes (OLEDs), especially those with an aggregation induced emission (AIE) feature.
Near-infrared-II (NIR-II) dyes could be encapsulated by either exogenous or endogenous albumin to form stable complexes for deep tissue bioimaging. However, we still lack a complete understanding of the interaction mechanism of the dye@albumin complex. Studying this principle is essential to guide efficient dye synthesis and develop NIR-II probes with improved brightness, photostability,
etc
.
Methods:
Here, we screen and test the optical and chemical properties of dye@albumin fluorophores, and systematically investigate the binding sites and the relationship between dye structures and binding degree. Super-stable cyanine dye@albumin fluorophores are rationally obtained, and we also evaluate their pharmacokinetics and long-lasting NIR-II imaging abilities.
Results:
We identify several key parameters of cyanine dyes governing the supramolecular/covalent binding to albumin, including a six-membered ring with chlorine (Cl), the small size of side groups, and relatively high hydrophobicity. The tailored fluorophore (IR-780@albumin) exhibits much-improved photostability, serving as a long-lasting imaging probe for NIR-II bioimaging.
Conclusion:
Our study reveals that the chloride-containing cyanine dyes with the above-screened chemical structure (e.g. IR-780) could be lodged into albumin more efficiently, producing a much more stable fluorescent probe. Our finding partly solves the photobleaching issue of clinically-available cyanine dyes, enriching the probe library for NIR-II bioimaging and imaging-guided surgery.
Thermally activated delayed fluorescence (TADF) molecules with dual emission have great potential for use as single emitters in white organic light-emitting diodes (WOLEDs).
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