NIR Mitochondrial Fluorescent Probe for Visualizing SO2/Polarity in Drug Induced Inflammatory Mice.

SO2 and polarity are important microenvironmental parameters in cells, which are closely related to physiological activities in organisms. The intracellular levels of SO2 and polarity are abnormal in inflammatory models. To this end, a novel near-infrared fluorescent probe BTHP that can simultaneously detect SO2 and polarity was studied. BTHP can sensitively detect polarity change with emission peak change from 677 to 818 nm. BTHP can also detect SO2 with fluorescence change from red to green. After addition of SO2, the fluorescence emission intensity ratio I517/I768 of the probe increased by about 33.6 times. BTHP can determine bisulfite in single crystal rock sugar with high recovery rate (99.2%-101.7%). Fluorescence imaging of cells showed that BTHP could better target mitochondria and monitor exogenous SO2 in A549 cells. More importantly, BTHP has been successfully used for dual channel monitoring SO2 and polarity in drug-induced inflammatory cells and mice. In particular, the probe showed increased green fluorescence with the generation of SO2 and increased red fluorescence with the decrease of polarity in inflammatory cells and mice.

Er-Based Luminescent Nanothermometer to Explore the Real-Time Temperature of Cells under External Stimuli.

Temperature as a typical parameter, which influences the status of living creatures, is essential to life activities and indicates the initial cellular activities. In recent years, the rapid development of nanotechnology provides a new tool for studying temperature variation at the micro- or nano-scales. In this study, an important phenomenon is observed at the cell level using luminescent probes to explore intracellular temperature changes, based on Yb-Er doping nanoparticles with special upconversion readout mode and intensity ratio signals (I525 and I545 ). Further optimization of this four-layer core-shell ratio nanothermometer endows it with remarkable characteristics: super photostability, sensitivity, and protection owing to the shell. Thus this kind of thermal probe has the property of anti-interference to the complex chemical environment, responding exclusively to temperature, when it is used in liquid and cells to reflect external temperature changes at the nanoscale. The intracellular temperature of living RAW and CAOV3 cells are observed to have a resistance mechanism to external stimuli and approach a more favorable temperature, especially for CAOV3 cells with good heat resistance, with the intracellular temperature 4.8 °C higher than incubated medium under 5 °C environment, and 4.4 °C lower than the medium under 60 °C environment.

Coumarin-based fluorescent probes toward viscosity in mitochondrion/lysosome.

Viscosity is an important microenvironmental indicator that plays an important role in the process of information transmission in various regions. Herein, two coumarin-based viscosity-sensitive fluorescent probes (CHB, CHN) were synthesized and the photophysical properties of the two probes were studied. The fluorescence quantum yields of CHB and CHN in glycerol can be as high as 25.2% and 18.3% respectively. The two probes can linearly detect viscosity in the viscosity logarithm range of 0.83-2.07, which is not interfered with pH, metal ions, anions and biomolecules. Fluorescent confocal cell experiments show CHB and CHN have good targeting ability to mitochondrion, lysosome, Endoplasmic reticulum and Golgi apparatus, and can be used to detect viscosity in mitochondrion/lysosome.

Colorimetric and Ratiometric Fluorescence Detection of HSO3- With a NIR Fluorescent Dye.

Bisulfite (HSO3-) has been widely used in food and industry, which has brought convenience to human life, but also seriously endangered human health. In this work, the probe PBI was designed and synthesized to detect bisulfite (HSO3-) through nucleophilic addition reaction. The probe PBI showed a selective reaction to HSO3- and can quantitatively detect HSO3-. At the same time, the color of the probe PBI changed significantly, which provided a simple method for the naked eye to identify HSO3-. Finally, it was successfully applied to the fluorescence imaging of HSO3- in living cells.

Preparation of Yellow Fluorescent N,O-CDs and its Application in Detection of ClO.

Accurate and efficient detection of ClO- was extremely important due to the harm of ROS in the environment and organism. In this paper, yellow fluorescent N,O-CDs were successfully prepared by the solvothermal method. The microscopic size of the N,O-CDs was approximately spherical with an average particle size of 4.8 ± 0.8 nm. The fluorescence quantum yield in ethanol solution was calculated as 10.5 % using fluorescein as the standard reference. The as-fabricated N,O-CDs had high sensitivity and low detection limit (7.5 µM) for quantitatively detecting ClO- with a linear range from 0.07 mM to 0.16 mM. The probe not only shows good selectivity and anti-interference to metal ions, anions and amino acids but also has excellent light stability and thermal stability. Also, a wide selection range for pH was demonstrated.

Carbon-dot-based ratiometric fluorescent probe of intracellular zinc ion and persulfate ion with low dark toxicity.

Metal ions and anions play significant roles in biological systems and industrial processes, therefore it is important to develop good fluorescent probes to detect metal ions and anions. Here, N,O-co-doped carbon quantum dots (CDs) that could detect Zn2+ via a ratiometric fluorescence method were fabricated. The reaction between the as-prepared CDs and zinc acetate gave the composite CDs-Zn, in which fluorescence changed ratiometrically upon addition of S2 O8 2- . With change in excitation light, the emission peaks of the CDs and CDs-Zn were kept fixed while intensity changed. CDs and CDs-Zn exhibited good photostability, thermal stability, selectivity, and strong anti-interference ability. In addition, CDs and CDs-Zn displayed low dark toxicity under physiological temperatures. Ratiometric fluorescence imaging of intracellular Zn2+ and S2 O8 2- was carried out in living HeLa cells for both of these probes. Compared with reported ratiometric fluorescent hybrid nanosensors based on organic dyes and inorganic nanomaterials, the as-prepared CDs and CDs-Zn had low toxicity, and were easy to synthesize.

NIR Ratiometric Luminescence Detection of pH Fluctuation in Living Cells with Hemicyanine Derivative-Assembled Upconversion Nanophosphors.

It is crucial for cell physiology to keep the homeostasis of pH, and it is highly demanded yet challenging to develop luminescence resonance energy transfer (LRET)-based near-infrared (NIR) ratiometric luminescent sensor for the detection of pH fluctuation with NIR excitation. As promising energy donors for LRET, upconversion nanoparticles (UCNPs) have been widely used to fabricate nanosensors, but the relatively low LRET efficiency limits their application in bioassay. To improve the LRET efficiency, core/shell/shell structured ß-NaGdF4@NaYF4:Yb,Tm@NaYF4 UCNPs were prepared and decorated with hemicyanine dyes as an LRET-based NIR ratiometric luminescent pH fluctuation-nanosensor for the first time. The as-developed nanosensor not only exhibits good antidisturbance ability, but it also can reversibly sense pH and linearly sense pH in a range of 6.0-9.0 and 6.8-9.0 from absorption and upconversion emission spectra, respectively. In addition, the nanosensor displays low dark toxicity under physiological temperature, indicating good biocompatibility. Furthermore, live cell imaging results revealed that the sensor can selectively monitor pH fluctuation via ratiometric upconversion luminescence behavior.

Naked-eye detection of C1-C4 alcohols based on ground-state intramolecular proton transfer.

Previous reports of fluorescent sensors for alcohols based on charge-transfer character of their excited state are based on mono-, di-, and tetra-phosphonate cavitands, which are capable of selecting analytes through shape/size selection and various specific H-bonding, CH-π, and cation-dipole interactions. To contrast, color changes based on absorption properties of the ground state are more suitable for direct observation with the naked eye. Three sensitive and selective colorimetric sensors for C1-C4 alcohols have been developed on the basis of alcohol-mediated ground-state intramolecular proton transfer. Reverse proton transfer induced by water achieves a fully reversible reaction. In addition, the solvent color indicates alcohol concentration.

Constructing metal nanoparticle multilayers with polyphenylene dendrimer/gold nanoparticles via "click" chemistry.

Multilayer films composed of azide-functional polymer and polyphenylene dendrimer-stabilized gold nanoparticles with alkynes in their peripheries have been fabricated using a layer-by-layer (LBL) approach via "click" chemistry. This method permits facile covalent linking of the polymer/nanoparticle interlayers in the mixture of DMF and water, which provides a general and powerful technique for preparing uniform nanoparticle (NP) thin films. The deposition process is linearly related to the number of bilayers as monitored by UV-vis spectroscopy. The multilayer structure and morphology have been characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and contact angle.

A dual-responsive crimson fluorescent probe for real-time diagnosis of alcoholic acute liver injury.

The polarity and viscosity of the microenvironment are associated with the control of the onset and progression of pathological diseases, including inflammation, immuno-suppression and cancer. If appropriate treatment is neglected, alcoholic acute liver injury (AALI), the initial sign of alcoholic liver diseases, may transform into hepatic lesions. Therefore, it's crucial to create a particular probe to detect AALI swiftly and track its progression. Herein a polarity and viscosity dual-responsive crimson fluorescent probe (PPBI) was designed and developed, which can target mitochondria and lipid droplets. PPBI possesses aggregation-induced emission properties, good photostability and strong anti-interference ability against pH, metal ions, anions and biomolecules. This probe can distinguish cancer cells from normal ones using changes of green and red fluorescence, as well as identify changes in the cellular microenvironment associated with inflammatory and ferroptosis processes. In addition, changes in polarity and viscosity can be amplified by in vivo imaging in a mouse model to monitor alcohol-induced acute liver injury and to effectively detect the course of pharmacological intervention therapy. All the results suggest that PPBI could be a promising real-time fluorescence imaging tool for diagnosis and treatment of acute alcoholic liver injury.

1,8-naphthyridine-derived Ni(2+)/Cu(2+)-selective fluorescent chemosensor with different charge transfer processses.

A highly fluorescent chemosensor based on 1,8-naphthyridine with high sensitivity and selectivity toward Ni(2+)/Cu(2+) over other cations both in aqueous solution over a wide pH range (4-10) and in cellular environments was developed. Counteranions such as acetate, sulfate, nitrate, and perchlorate have no influence on the detection of such metal ions. Ethylenediamine showed high selectivity toward the in situ-prepared Cu(2+) complex over the Ni(2+) complex, which can be applied to distinguish Ni(2+) and Cu(2+). The Ni(2+)-induced fluorescence on-off mechanism was revealed to be mediated by intramolecular charge transfer from the metal to the ligand, while that by Cu(2+) involves intramolecular charge transfer from the ligand to the metal, as confirmed by picosecond time-resolved fluorescence spectroscopy and time-dependent density functional theory calculations.

A mitochondrial and lysosomal targeted ratiometric probe for detecting intracellular H2S.

Based on coumarin and benzopyran derivatives, a dual-wavelength excitation ratiometric fluorescent probe, HABA, was prepared to detect H2S. The HABA probe showed good selectivity and anti-interference abilities during H2S detection. Fluorescence co-localization experiments showed that HABA had excellent localization abilities toward mitochondria and lysosomes. More importantly, HABA can not only detect exogenous H2S, but it can also detect endogenous H2S, indicating that HABA has high application potential and value in the biological field.

Multiple organelle-targeted near-infrared fluorescent probes toward pH and viscosity.

Organelles, including mitochondria (mito), lysosomes (lyso), endoplasmic reticulum (ER), Golgi apparatus (Golgi), and ribosome et al., play a vital role in maintaining the regular work of the cell. Viscosity is an essential parameter in the cellular microenvironment. Herein, four viscosity-sensitive near-infrared fluorescent probes DMPC, DEPC, DHDM and DHDV that can simultaneously target multiple organelles were synthesized. As the viscosity increased, the fluorescence intensity of the probes gradually increased due to the hindrance of the rotation of the carbon-carbon single bond. The fluorescence intensity of DHDV increased by about 453 times, and the fluorescence quantum yield also increased from 0.051 to 0.681. Cell experiments indicated the probes could simultaneously target four kinds of organelles, and the four probes could also track mitochondria with no dependence on membrane potential. Further experiments showed that the probes could detect viscosity changes in lyso and mito. In addition, the probes also demonstrated the advantages of low cytotoxicity, good anti-interference and stability, providing a simple and effective tool for studying the activity of organelles with changing viscosity signals.

Imaging of intracellular bisulfate based on sensitive ratiometric fluorescent probes.

Sulfur dioxide (SO2) is an environmental pollutant in the atmosphere which is easily absorbed by the human body. After being inhaled in the body, SO2 is quickly converted into bisulfite (HSO3-), forming a balance in which SO2 and HSO3- coexist in the body status. A large number of epidemiological studies have shown that abnormal levels of sulfite and bisulfite are related to the appearance of numerous diseases such as atherosclerosis, essential hypertension, and lung tissue fibrosis. Therefore, it is essential to develop an effective method to detect bisulfite. In this work, starting from 4-bromonaphthalene-1-carbonitrile, three uncomplicated but efficient HSO3- sensitive ratiometric fluorescent probes HNIC, CIVP and HVIC were designed and synthesized through ICT mechanism and the Michael-type addition reaction. The probes can image HSO3- in living cells. The probes not only have good fluorescence stability and strong anti-interference ability, but also display mitochondrial targeting ability.

One-step synthesis of mitochondrion-targeted fluorescent carbon dots and fluorescence detection of silver ions.

Silver ions (Ag+) are the most representative harmful ions found in polluted water and widely used in many industries; excessive ingestion of Ag+ in the human body may result in interaction with different metabolites in the human body and in aquatic microorganisms, leading to many diseases. Therefore, there is a great desire to develop good fluorescent probes for Ag+. Herein, a kind of mitochondrion-targeted fluorescent carbon dot was developed. These carbon dots exhibit 29.5% fluorescence quantum yield in water, good photostability and thermal stability. The as-fabricated carbon dots can quickly detect Ag+ in 100% water solution with good selectivity and anti-interference ability. Further, the carbon dots have been successfully applied to monitor Ag+ in living cells via the dual-channel method.

A mitochondrion-targeting fluorescent probe for hypochlorite anion in living cells.

As momentous reactive oxygen species (ROS), it is necessary to develop high-sensitivity and high-specificity fluorescent probes for tracking hypochlorite anion (ClO-) in environmental and biological systems. Herein, a kind of red luminescent carbon dots (NS-dots) was synthesized by one-step solvothermal method to detect ClO- in PBS buffer solution (VPBS:VEtOH = 100:1, pH = 7.4). The NS-dots has high sensitivity and low detection limit (13.3 µmol/L) for detecting ClO- with linear range from 6.7 × 10-5 mol/L to 26.7 × 10-5 mol/L. Using Rhodamine B (31% at 520 nm in water) as a reference, the NS-dots have a fluorescence quantum yield of 7.2%. Intracellular photostability, mitochondrial targeting properties and the fluorescence imaging towards intracellular ClO- were demonstrated.

Measurement of Temperature Distribution at the Nanoscale with Luminescent Probes Based on Lanthanide Nanoparticles and Quantum Dots.

It is very challenging to probe the temperature in a nanoscale because of the lack of detection technique. Temperature-sensitive luminescent probes at a nanoscale provide the possibility to solve this problem. Herein, we fabricated a model, which combined two kinds of temperature sensitive nanoprobes and gold nanoparticle heater within mesoporous silica nanoparticles. Upconverting nanoparticles and quantum dots located at different positions inside 110 nm nanoparticles reported different temperatures when the gold nanoparticles generated heat by 532 nm laser irradiation. The temperature difference between two probes with an average distance of 55 nm can reach about 30 °C. Our results prove that the temperature distribution at a nanoscale can be measured, and it will be noteworthy if a nano-heater is applied.

Intramolecular charge transfer in 5-methoxy-2-(2-pyridyl)thiazole-derived fluorescent molecules with different acceptor or donor substituents.

On the basis of the rational derivation of 5-methoxy-2-(2-pyridyl)thiazole (2-MPT), we synthesized a new series of charge-transfer-based fluorescent molecules bearing different electronic donors or acceptors. The substituents range from strong electronic donors (e.g., amino and hydroxyl groups) to weak donating groups (e.g., proton and methyl groups) and electronic acceptors (e.g., pyridine ring). Through systematic investigation on the substituent-/polarity-dependent spectra (including room-temperature absorption, room-/low-temperature steady-state fluorescence spectra, and transient fluorescence lifetime characterization) and theoretical calculations, the emission properties of MPT derivatives are found to be governed by the rotation of the substituent around the triple bond axis, which produces distinct intramolecular charge transfer processes in either the twisted or planar excited states. The interconversion of excited-state geometry triggered by local interactions in polar solvents may produce a bathochromic shift of approximately 100 nm in fluorescence spectra. The solution state may also affect the ground- and excited-state conformation and hence results in the solvent-frozen-point sensitive fluorescence for some of the as-prepared molecules.

Diaqua-{6,6'-dimeth-oxy-2,2'-[ethane-1,2-diylbis(nitrilo-methyl-idyne)]diphenolato-κO,N,N',O'}manganese(III) perchlorate 18-crown-6 hemisolvate monohydrate.

In the cation of the title compound, [Mn(C(18)H(18)N(2)O(4))(H(2)O)(2)]ClO(4)·0.5C(12)H(24)O(6)·H(2)O, the Mn(III) ion is coordinated by two water O atoms, and two O atoms and two N atoms from the tetradentate 6,6'-dimeth-oxy-2,2'-[ethane-1,2-diylbis(nitrilo-methyl-idyne)]di-phenolate ligand, completing a distorted octa-hedral geometry. One O atom of the 18-crown-6-ether is disordered over two positions with occupancies of 0.70 (2) and 0.30 (2).

{6,6'-Dimeth-oxy-2,2'-[4-bromo-o-phenyl-enebis(nitrilo-methyl-idyne)]diphenolato}nickel(II) methanol solvate.

In the title compound, [Ni(C(22)H(17)BrN(2)O(4))]·CH(3)OH, the Ni(II) ion is in a slightly distorted square-planar geometry involving an N(2)O(2) atom set of the tetra-dentate Schiff base ligand. The asymmetric unit contains one nickel complex and one methanol solvent mol-ecule. The dihedral angle between the aromatic ring planes of the central aromatic ring and other two aromatic rings are 10.8 (3) and 6.0 (2)°. The crystal structure is stabilized by inter-molecular C-H⋯O and C-H⋯Br and by intra-molecular O-H⋯O hydrogen bonds.