Yuming Yang,†,§ Qiang Zhao,‡,§ Wei Feng,† and Fuyou Li*,† †Department of Chemistry and State Key Laboratory of Molecular Engineering of Polymers and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, P. R. China ‡Key Laboratory for Organic Electronics and Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210046, P. R. China.

Luminescent chemodosimeters for bioimaging.

The long wavelength (far-red to NIR) analyte-responsive fluorescent probes are advantageous for in vivo bioimaging because of minimum photo-damage to biological samples, deep tissue penetration, and minimum interference from background auto-fluorescence by biomolecules in the living systems. Thus, great interest in the development of new long wavelength analyte-responsive fluorescent probes has emerged in recent years. This review highlights the advances in the development of far-red to NIR fluorescent probes since 2000, and the probes are classified according to their organic dye platforms into various categories, including cyanines, rhodamine analogues, BODIPYs, squaraines, and other types (240 references).

Far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging

Design strategies for water-soluble small molecular chromogenic and fluorogenic probes.

We developed a highly selective ratiometric near-infrared cyanine-based probe CyAC for cysteine (Cys) over homocysteine (Hcy) and glutathione (GSH). Upon the addition of Cys to the solution of CyAC, remarkable shifts in the spectra of CyAC can be monitored (from 770 nm to 515 nm in absorption spectra and from 780 nm to 570 nm in emission spectra). For the first time, the novel strategy that reversibly modulates the polymethine π-electron system by conjugation and removal of the specific trigger moiety was implemented for the generation of a ratiometric cyanine-based sensor. Hydroxy cyanine CyAE was chosen as the flurophore scaffold because the tautomerism (CyAE and CyAK or CyAD) can cause the reversible change in the π-conjugation system of the dyes with large shifts in the spectra. An acrylate group containing a α, β-unsaturated ketone as a functional trigger moiety was incorporated with CyAK to form the sensor CyAC. This specific response for Cys was based on the differences of the kinetics of intramolecular adduct/cyclizations. Moreover, CyAC was successfully applied for bioimaging Cys in living cancer cells. This paradigm by modulation of the polymethine π-electron system in the cyanine dye provides a promising methodology for the design of ratiometric cyanine-based sensors.

http://dspace.ewha.ac.kr/bitstream/2015.oak/222878/1/001.pdf

A highly selective ratiometric near-infrared fluorescent cyanine sensor for cysteine with remarkable shift and its application in bioimaging

Chemodosimeters: An approach for detection and estimation of biologically and medically relevant metal ions, anions and thiols

Discrimination between chemically related benzenethiols and aliphatic thiols represents a big problem. In this paper, a fluorescent probe, Bodipy-1, containing an indole-based Bodipy as a fluorophore and a 2,4-dinitrobenzenesulfonyl group as a recognition unit was constructed to achieve the selectivity between them. The Bodipy group in the prepared probe was selectively released through aromatic nucleophilic substitution by thiolate anions from benzenethiols, resulting in blue−red switching in the emission spectra in buffer solutions; that is, two new peaks of the phenol/phenolate state of Bodipy-2 at 565 and 629 nm appeared in emission spectra. By varying the pH value from 6.6 to 8.8, the intensity ratio of I565/I629 varies from 2.0 to 0.3 after complete conversion to Bodipy-2, a ca. 7-fold emission ratio change. This ratiometric emission property by varying the pH value makes Bodipy-1 a promising probe to discriminate benzenethiols from aliphatic thiols by careful selection of the reaction pH.

Development of an indole-based boron-dipyrromethene fluorescent probe for benzenethiols.

A colorimetric and fluorescent turn-on chemodosimeter for fluoride with high selectivity was developed on the basis of the specific reaction of F− with BODIPY-OSi, displaying a dramatic color change and distinct near-infrared (NIR) fluorescence enhancement at 676 nm.

A colorimetric and ratiometric NIR fluorescent turn-on fluoride chemodosimeter based on BODIPY derivatives: high selectivity via specific Si–O cleavage

A borondipyrromethene-based Zn2+ fluorescent probe BODPAQ was designed and synthesized. The chelators in BODPAQ, 2,2′-dipicolylamine (DPA) and 8-aminoquinoline (AQ), coordinate to Zn2+ in a synergic manner. As a result, BODPAQ displays high Zn2+ selectivity with a dramatic enhanced emission accompanied by a notable hypsochromic shift due to the binary inhibition effect of PET and ICT mechanisms, enabling the detection of Zn2+ by both ratiometric and normal turn-on fluorescence methods in acetonitrile. Interestingly, the sensitivity of BODPAQ towards Zn2+ changes upon varying the compositions of buffer solutions. In 3-morpholinopropanesulfonic acid (MOPS) buffer aqueous solution (50% CH3CN), BODPAQ displays the highest sensitivity for Zn2+, while in citrate–phosphate buffer, BODPAQ shows no response to Zn2+.

Development of a borondipyrromethene-based Zn2+ fluorescent probe: solvent effects on modulation sensing ability

Here, we report a new Cu(2+)-selective fluorescent turn-on probe BODIPY-EP, in which the 2-pyridinecarboxylic acid is connected to a 6-hydroxyindole-based BODIPY platform through an ester linkage The ester bond of BODIPY-EP is selectively hydrolyzed by the reaction with Cu(2+) under mild and neutral conditions to generate BODIPY-OH, showing strong characteristic fluorescence of BODIPY-OH The favorable features of BODIPY-EP towards Cu(2+) include fast response, large fluorescence enhancement and high selectivity We further demonstrated that the membrane-permeable probe reacts with intracellular Cu(2+) and exhibits bright fluorescence in living cells

Borondipyrromethene-derived Cu2+ sensing chemodosimeter for fast and selective detection

A 6-hydroxyindole-based BODIPY, named BODIPY–OH, with distinct spectroscopic characteristics is reported. Through a systematic study of the spectroscopic characteristics of BODIPY–OH and BODIPY–O− in various solvents containing an organic base, we found that the light-color of the fluorophore can be tuned over a wide range by changing the polarity of solvent/base combinations. The absorption color of the solution can be tuned over a range of 100 nm and the emission color within a wide range from 571 to 681 nm by simply converting the phenol form of BODIPY–OH to the phenolate form. Fluorescence of BODIPY–O− with high quantum yield shows relatively large Stokes shift in solvent/base combinations, which are ascribed to the excited state deprotonation from (BODIPY–OH)* to (BODIPY–O−)*, followed by emission from the ion form.

Yulin Zhang

Papers

Development of an indole-based boron-dipyrromethene fluorescent probe for benzenethiols.

A colorimetric and ratiometric NIR fluorescent turn-on fluoride chemodosimeter based on BODIPY derivatives: high selectivity via specific Si–O cleavage

Development of a borondipyrromethene-based Zn2+ fluorescent probe: solvent effects on modulation sensing ability

Borondipyrromethene-derived Cu2+ sensing chemodosimeter for fast and selective detection

6-Hydroxyindole-based borondipyrromethene: Synthesis and spectroscopic studies