Real-Time Monitoring of Endogenous Cysteine Levels In Vivo by near-Infrared Turn-on Fluorescent Probe with Large Stokes Shift

Abstract

Cysteine (Cys), as an important biothiol, plays a major role in many physiological processes like protein synthesis, detoxification and metabolism, and also is closely associated with a variety of diseases; thus the design of novel highly selective and sensitive near-infrared (NIR) fluorescent probes for Cys detection in vivo is of great significance. Herein, we report a selective and sensitive NIR turn-on fluorescent probe (CP-NIR) with large Stokes shift for detecting Cys in vivo. Upon addition of Cys to the solution of the probe, it is absorption wavelength shifts from 550 to 600 nm, accompanying with an obvious enhancement of NIR fluorescence emission centering around 760 nm. This Michael-addition reaction-based probe shows a large Stokes shift (160 nm), low detection limit (48 nM), fast response time, and low toxicity. Moreover, this novel NIR probe with good cell permeability was successfully applied to monitoring endogenous Cys in living cells and in a mouse model.

Development of Lysosome‐Targeted Fluorescent Probes for Cys by Regulating the Boron‐dipyrromethene (BODIPY) Molecular Structure

“…These observations correlatedw ell with previous reports describing the larger concentration of thiolates peciesi nh igher pH environments. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Lysosomes are spherical-shaped, catabolic organelles with an acidic interior (pH 4.0-6.0). [63] Although diminished reactivity towards Cys was found, both Lyso-S and Lyso-D could functionp roperly under al ysosomal pH environment.…”

“…Al arge number of innovative fluorescent probesh ave been discoveredt od istinguish and measureb iothiols [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] and some impressive works have succeeded in differentiating GSH from Cys and Hcy. [19][20][21][22][23][24][25][26][27] However,i ti ss till ac hallenge to construct probesf or discriminating Cys from Hcy owing to the similar pK a and steric congestion of Cys and Hcy,which also frequently suffers from drawbacks such as unsatisfactory selectivity,l ong responset ime, and undesired spectra overlap.…”

A Deep‐Red to Near Infrared (NIR) Fluorescent Probe Based on a Sulfur‐Modified Rhodamine Derivative with Two Spirolactone Rings

“…[1][2][3][4] High contrast image can also be achieved for the labeled target and the surrounding tissues due to the minimal tissue absorption and low background fluorescence in the NIR spectral range. [5][6][7][8] Many NIRexcitable scaffolds have been reported, [9][10][11] but their fluorescence quantum yield is limited in aqueous environments because of their poor water-solubility and the tendency for molecular stacking. Rhodamine derivatives possessing sensory behaviors with drastic color changes and fluorescence enhancement as selective and sensitive probes have been reported.…”

Fluorescent Imaging for Cysteine Detection In Vivo with High Selectivity

“…PÀ Cy was designed following a photo-induced electron transfer (PET) principle. [26,34,35] Merocyanine (CyÀ Ph) was used as chromophore due to its extraordinary optical properties [36] and acryloyl as recognition group. [26,37,38] When cysteine was absent, the PETinduced quenching effect caused inconspicuous florescence intensity (FI) of PÀ Cy.…”