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Given the wavelength dependence of tissue transparency and the requirement for sufficiently low background autofluorescence, the development of fluorescent dyes with excitation and emission maxima beyond 700 nm is highly desired, but it is a challenging task. Herein, a new class of fluorescent dyes, named sulfone-rhodamines (SO2Rs), was developed on the basis of the one-atom replacement of the rhodamine 10-position O atom by a sulfone group. Such a modification makes their absorption and emission maxima surprisingly reach up to 700-710 and 728-752 nm, respectively, much longer than their O-, C-, and Si-rhodamine analogs, due to the unusual d*-π* conjugation. Among these dyes, SO2R4 and SO2R5, bearing disubstituted meso-phenyl groups, show the greatest potentials for bioimaging applications in view of their wide pH range of application, high photostability, and big extinction coefficients and fluorescence quantum yields. They could quickly penetrate cells to give stable NIR fluorescence, even after continuous irradiation by a semiconductor laser, making them suitable candidates for time-lapse and long-term bioimaging applications. Moreover, they could specifically localize in lysosomes independent of alkylmorpholine targeted group, thus avoiding the problematic alkalization effect suffered by most LysoTrackers. Further imaging assays of frozen slices of rat kidney reveal that their tissue imaging depth is suprior to the widely used NIR labeling agent Cy5.5.

A novel multiheteroatom (N, O and P) [3,3]-sigmatropic rearrangement is disclosed, based on two important types of organophosphates, 2-(N-heteroaryl) methyl phosphates and α-keto phosphates, being accessed smoothly and efficiently.

A mitochondria-specific fluorescent probe for NO (1) was synthesized by the direct conjugation of a pyronin dye with one of the amino groups of o-phenylenediamino (OPD). The probe could selectively detect NO over dehydroascorbic acid (DHA), ascorbic acid (AA), and methylglyoxal (MGO) as well as the reactive oxygen/nitrogen species (ROS/RNS) with the significant off-on response due to the production of a red-emission triazole 2. In the presence of cysteine/glutathione (Cys/GSH), 2 could be further transformed into a green-emission aminopyronin 4 and a red-emission thiopyronin 5, respectively. Assisted by intracellular Cys and GSH, the probe demonstrated its potential to monitor mitochondrial NO in a dual-channel mode.

A but-3-yn-2-one-based 7-diethylaminocoumarin dye was exploited as a fluorescent probe to specifically detect Cys over Hcy/GSH in pure PBS buffer. The probe itself is nonfluorescent due to the donor-excited photoinduced electron transfer (d-PET) process. The Cys-induced Michael addition-rearrangement cascade reaction leads to an amino-substituted product with strong fluorescence due to inhibiting C[double bond, length as m-dash]C isomerization induced fluorescence quenching by a produced intramolecular N-HO hydrogen bond. The Hcy (or GSH)-induced Michael addition reaction leads to a thiol-substituted product (or ), which lacks any intramolecular hydrogen-bonding interaction, and thus displays very poor fluorescence due to the efficient C[double bond, length as m-dash]C isomerization induced fluorescence quenching. Even in the presence of Hcy (or GSH), the probe could also detect Cys with the obvious fluorescence enhancement. Assisted by using a laser scanning confocal microscope, we demonstrated that the probe could selectively image Cys in the human renal cell carcinoma 786-0 cells.

A carboxylic acid-functionalized coumarin-hemicyanine near-infrared (NIR) dye 1 was exploited, which possesses good water solubility (more than 50 μM) and favorable photophysical properties, especially a large Stokes shift (around 90 nm), and has been proved to be a suitable imaging agent for targeting mitochondria. With the dye platform, fluorescent probe 2, a thioester derivative of 1, was constructed for biothiols. Probe 2 can react with cysteine (Cys) via the native-chemical-ligation (NCL) and cyclization cascade reactions to lead to coumarin 2-Cys. However, the reaction of 2 with homocysteine (Hcy) or glutathione (GSH) only stays at the stage of the initial transthioesterification reaction, producing coumarin-hemicyanines 2-Hcy or 2-GSH, due to an electrostatic interaction in 2-Hcy and an unstable macrocyclic transition state in 2-GSH, both inhibiting their subsequent S,N-acyl shift. Given the distinct photophysical properties between 2-Cys and 2-Hcy (or 2-GSH), probe 2 could highly selectively discriminate Cys from Hcy/GSH. Even in the presence of Hcy or GSH, probe 2 still works well for Cys due to the reversible transthioesterification and the irreversible S,N-acyl shift in the NCL reaction. The cell imaging assays revealed that probe 2 is cell permeable and could selectively image Cys in living cells.

A chlorinated coumarin-hemicyanine dye with three potential reaction sites was exploited as fluorescent probe for biothiols. The Cys-induced substitution-rearrangement-cyclization, Hcy-induced substitution-rearrangement, and GSH-induced substitution-cyclizatioin cascades lead to the corresponding amino-coumarin, amino-coumarin-hemicyanine, thiol-coumarin with distinct photophysical properties, enabling Cys and GSH to be selectively detected from different emission channels at two different excitation wavelengths.

A Cu(II)-based 2 : 2 chemosensing ensemble bearing rhodamine B fluorophore was developed for fluorescence turn-on detection of CN− with high selectivity and sensitivity based on the CN− complexation to the Cu2+ centre in the nearly planar central binding moiety.

A regenerative, molecular machine-like "ON-OFF-ON" chemosensor based on a chromene molecule with the pyran ring "OFF-ON-OFF" cycle is reported for the first time. It behaves as a molecular lock that requires a thiol "key" to open the lock and a mercury(II) ion "hand" that unlatches the key for unsheathing the key to close the lock.

The optical properties of a novel, rhodamine-based derivative, synthesized by reacting rhodamine hydrazide and 5-chlorosalicylaldehyde in ethanol, were investigated in methanol:HEPES solution. The novel sensor displayed selectivity for Cu2+, as evidenced by a colourless to dark red colour change, which was characterized using UV–visible spectroscopy and which also allowed visual detection of Cu2+. In contrast, selectivity towards VO2+ was determined from changes in the emission spectra in the nanomolar range. This represents the first reported rhodamine-based sensor capable of detecting both Cu2+ and VO2+ using two different modes.

A new thiol-containing colorimetric probe has been developed by using a chromene derivative, 7-nitro-2,3-dihydro-1H-cyclopenta[b]chromen-1-one (1). The molecule exhibited high selectivity and sensitivity for detecting thiol species as cysteine, homocysteine, and glutathione in aqueous solution through a rapid visual color change from colorless to yellow.

A mitochondria-targetable fluorescence probe, methyl(4-hydroxyphenyl)amino-substituted pyronin (1), was exploited, which could highly selectively sense peroxynitrite (ONOO−) within seconds.

Colorful mixture: Three types of luciferin analogues, that is, alkylaminoluciferins, aminoselenoluciferin, and luciferins with a benzimidazole scaffold, have been reported. These analogues show excellent bioluminescent properties and great potential in bioluminescence imaging.

Probes to dye for: Rhodamine-inspired Si-pyronine, Si-rhodamine, Te-rhodamine, and Changsha NIR dyes have been developed recently. These dyes show fluorescence in the far-red to near-infrared region, while retaining the advantages of the original rhodamines, such as high fluorescence quantum yield, tolerance to photobleaching, good water solubility, and exhibit great potential for biological application.

Glutathione (GSH), the most abundant intracellular biothiol, protects cellular components from damage caused by free radicals and reactive oxygen species (ROS), and plays a crucial role in human pathologies. A fluorescent probe that can selectively sense intracellular GSH would be very valuable for understanding of its biological functions and mechanisms of diseases. In this work, a 3,4-dimethoxythiophenol-substituted coumarin-enone was exploited as a reaction-type fluorescent probe for GSH based on a chloro-functionalized coumarin-enone platform. In the probe, the 3,4-dimethoxythiophenol group functions not only as a fluorescence quencher through photoinduced electron transfer (PET) to ensure a low background fluorescence, but also as a reactive site for biothiols. The probe displays a dramatic fluorescence turn-on response toward GSH with the long-wavelength emission (600 nm) and significant Stokes shift (100 nm). The selectivity of the probe toward GSH over cysteine (Cys), homocysteine (Hcy), and other amino acids was demonstrated. Assisted by laser-scanning confocal microscopy, we have demonstrated that the probe could specifically sense GSH over Cys/Hcy in human renal cell carcinoma SiHa cells.

A new cyanide anion colorimetric probe was developed using a chromene derivative, 7-nitro-2,3-dihydro-1H-cyclopenta[b]chromen-1-one (1). The molecule exhibited much higher selectivity and sensitivi...

A strategy for the determination of the presence of thiol-containing amino acids was successfully established by simply assembling copper chloride and xylenol orange (3,3'-bis[N,N-bis(carboxymethyl)aminomethyl]-o-cresolsulfonephthalein trisodium salt; XO) in a 1 : 1 molar ratio in quasi-physiological water solution (pH 6.0). The copper(II)-XO ensemble was highly selective for thiol species such as cysteine, homocysteine, and glutathione without interference from other amino acids and could quantitatively detect thiol in the range from 10 to 200 μM with a linear relationship having an average molar absorbance constant of 6530 L mol(-1) cm(-1) in pure water. The whole recognition process for thiol gave rise to a rapid visual color change from purple-red to yellow which can be observed simultaneously with the naked-eye.

A novel strategy for the determination of oxalate anions was successfully established using a copper ion and pyrocatechol violet (PV) ensemble. The sensor ensemble can discriminate oxalate over other common anions including F(-), Cl(-), I(-), Br(-), HPO(4)(2-), PO(4)(3-), AcO(-), CO(3)(2-), SO(4)(2-), ClO(4)(-), P(2)O(7)(4-), S(2-) (deposited by Ag(+)), CN(-) (shielded by Fe(3+)) and can detect oxalate at low microgram levels in quasi-physiological aqueous solutions. The detection of the oxalate anion gives rise to a rapid observable visual color change from blue to yellow.

A 4-methoxythiophenol-substituted pyronin dye 1 was exploited as reaction-type fluorescent probe for biothiols Cys/Hcy and GSH. The probe itself is nonfluorescent due to the photoinduced electron transfer (PET) process. The Cys (or Hcy)-induced substitution–rearrangement cascade reaction and GSH-induced substitution reaction with the probe lead to the corresponding aminopyronin and thiopyronin dyes with distinct photophysical properties, enabling Cys/Hcy and GSH to be detected from visible and near-infrared (NIR) emission channels, respectively, in pure PB buffer with relatively fast kinetics and obvious fluorescence turn-on response. Assisted by laser scanning confocal microscope, we also demonstrated that probe 1 could simultaneously sense Cys/Hcy and GSH in B16 cells in multicolor imaging.

A rhodamine-inspired fluorescence dye (2) bearing 7-diethylaminocoumarin fluorophore was designed as a platform for the construction of an NIR and ratiometric fluorescent probe. The ring-open form of 2 shows NIR absorption and emission; however, its ring-closed form displays the visible absorption and emission because an intact 7-diethylaminocoumarin fluorophore was involved in the structure, providing the basis for an NIR and ratiometric fluorescent platform based on the spirocyclization-induced fluorescence switching mechanism. With the platform, we developed a novel NIR and ratiometric fluorescent probe R1, a thiolactone of 2, for sensing Hg2+, an environmentally and biologically concerned species. R1 displays an emission peak with the maximum at 480 nm, which is the typical emission of 7-diethylaminocoumarin moiety; however, upon addition of Hg2+ ions, the emission intensity at 480 nm gradually decreased with the simultaneous appearance of a new NIR emission band centred at 695 nm. Thus, the Hg2+-promoted ratiometric fluorescence response can be realized. The high selectivity towards Hg2+ over various cations and the high stability in a wide pH range of 1–12 indicate its potential for applications in biological systems. The subsequent cell imaging experiment revealed that R1 is cell permeable, and could be employed for ratiometric fluorescence imaging of Hg2+ in living cells.

A fluorescent turn-on probe for H2S was exploited based on a H2S-induced substitution-cyclization cascade reaction towards the bis-electrophilic centers of a new H2S trap group 2-(iodomethyl)benzoate.

A coumarin-hemicyanine dye was reported for ratiometric fluorescent detection of SO2 derivatives HSO3(-) and SO3(2-) based on a novel addition-rearrangement cascade reaction.

A fluorescence turn-on probe for bisulfite has been developed by taking advantage of the specific reaction of bisulfite and aldehyde in combination with the hydrogen bond inhibited C=N isomerization mechanism. The practical value of this selective and sensitive fluorescent probe was confirmed by its application to detection of bisulfite in granulated sugar.

A new ratiometric fluorescent cyanide probe was developed based on the nucleophilic attack of CN(-) toward the indolium group of a hybrid coumarin-hemicyanine dye, by which high selectivity as well as large emission shift could be achieved.