Bent-to-planar Si-rhodamines: a distinct rehybridization lights up NIR-II fluorescence for tracking nitric oxide in the Alzheimer's disease brain.

An ongoing revolution in fluorescence-based technologies has transformed the way we visualize and manipulate biological events. An enduring goal in this field is to explore high-performance fluorogenic scaffolds that show tunability and capability for in vivo analysis, especially for small-molecular near-infrared (NIR) fluorophores. We present a unique bent-to-planar rehybridization design strategy for NIR fluorogenic scaffolds, thus yielding a palette of switchable bent/planar Si-rhodamines that span from visible to NIR-II wavelengths. We demonstrate that the rehybridization of meso-nitrogen in this innovative NIR scaffold Cl-SiRhd results in flipping between the disruption and recovery of the polymethine π-electron system, thereby significantly altering the spectral wavelength with crosstalk-free responses. Using elaborately lighting-up NIR-II probes with ultra-large Stokes shifts (ca. 250 nm), we successfully achieve real-time in situ monitoring of biological events in live cells, zebrafish, and mice. Notably, for the first time, the light-up NIR-II probe makes a breakthrough in directly in situ tracking nitric oxide (NO) fluctuations in the brains of mice with Alzheimer's disease. This de novo bent-to-planar rehybridization strategy of NIR-II probes opens up exciting opportunities for expanding the in vivo imaging toolbox in both life science research and clinical applications.

Rational Design of Ratiometric Near-Infrared Aza-BODIPY-Based Fluorescent Probe for in Vivo Imaging of Endogenous Hydrogen Peroxide.

Precise in vivo tracking of hydrogen peroxide is still challenging due to its dynamic complexity and intrinsic background interference. Herein, we describe a rational design strategy to construct asymmetric aza-boron-dipyrromethane derivative (BODIPY)-based ratiometric probes for in vivo tracking H2O2, which are composed of a near-infrared aza-BODIPY core, active targeting group, and H2O2-specific recognition unit. We take advantage of two terminal functionalized conjunctions in the bis-condensed aza-BODIPY by rationally introducing carbonyl group as an electron-deficiency linker for regulating intramolecular charge transfer-induced wavelength shift and by attaching hydrophilic polyethylene glycol-biotin segment as the active targeting moiety. The probe BP5-NB-OB features several striking characteristics: (i) ratiometric near infrared response in both absorption and emission spectra; (ii) active targeting ability (biotin receptor-mediated endocytosis) with excellent biocompatibility; and (iii) in vivo tracking of endogenous H2O2. It was demonstrated that the probe BP5-NB-OB was successfully utilized for tracking endogenous H2O2 in living cells and tumor-bearing mice, providing opportunities to insight into H2O2 related diseases for clinical application.