Turn-on Fluorescence Emission Research Articles

Development of a hybrid rhodamine-hydrazine NIR fluorescent probe for sensitive detection and imaging of peroxynitrite in necrotizing enterocolitis model

This study describes the synthesis and characterization of a novel near-infrared (NIR) fluorescent probe RBNE based on a hybrid rhodamine dye, which shows excellent optical capability for detecting and imaging ONOO− in necrotizing enterocolitis (NEC) mouse model. The probe RBNE undergoes hydrazine redox-process, and subsequently the spirocyclic structure’s opening, resulting in a turn-on fluorescence emission with the presence of ONOO−, which exhibits several excellent features, including a significant Stokes shift of 108 nm, near-infrared emission at 668 nm, a lower detection limit of 56 nM, low cytotoxicity, and excellent imaging ability for ONOO− both in vitro and in vivo. The presented study introduces a novel optical tool that has the potential to significantly advance our understanding of peroxynitrite (ONOO−) behaviors in necrotizing enterocolitis (NEC).

Through bond energy transfer (TBET)-based chemosensor with large Stokes shift for colorimetric and fluorogenic determination of Fe3+ in aqueous system and intracellular imaging application

Chemosensor based on through-bond energy transfer (TBET) mechanism with triazaborolopyridinium (TBP) fluorophore as energy donor and rhodamine fluorophore as energy acceptor was designed, and its Fe3+ ion sensing properties were investigated in aqueous media. Prominent change of solution from yellow to pink and turn-on fluorescence emission was realized by employing Fe3+ selective recognition to form a Fe3+-rhodamine conjugate giving rise to emission at 590 nm with a large Stokes shift (210 nm) under the excitation at 380 nm. This sensor was highly selective and sensitive for distinguishing Fe3+ ions from other common cations. Interestingly, the achieved chemosensor exhibits the detection limits of 32 ppb and 14 ppb for chromogenic and fluorometric analysis, respectively, which are lower than the WHO and U.S. EPA permissible levels in drinking water. The reversible behavior of the Fe3+-sensor complex with the alternate additions of hydrazine and Fe3+ could establish the potential reusability. Moreover, the sensor has also been successfully applied for imaging the presence of Fe3+ ions in living cells.

Time-Dependent Solvent-Driven Solid-State Fluorescence-based Numeric Coding.

Controllable solid-state transformations can provide a basis for novel functional materials. Herein, we report a series of solid-state systems that can be readily transformed between amorphous, co-crystalline, and mixed crystalline states via grinding or exposure to solvent vapors. The present solid materials were constructed using an all-hydrocarbon macrocycle, cyclo[8](1,3-(4,6-dimethyl)benzene) (D4d-CDMB-8) (host), and neutral aggregation-caused quenching dyes (guests), including 9,10-dibromoanthracene (1), 1,8-naphtholactam (2), diisobutyl perylene-3,9-dicarboxylate (3), 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (4), 4,7-di(2-thienyl)-benzo[2,1,3]thiadiazole (5), and 4-imino-3-(pyridin-2-yl)-4H-quinolizine-1-carbonitrile (6). Seven co-crystals and six amorphous materials were obtained via host-guest complexation. Most of these materials displayed turn-on fluorescence emission (up to 20-fold enhancement relative to the corresponding solid-state guests). The interconversion between amorphous, co-crystalline states, and crystalline mixtures could be induced by exposure to solvent vapors or by subjecting to grinding. The transformations could be monitored readily by means of single-crystal and powder X-ray diffraction analyses, as well as solid-state fluorescent emission spectroscopy. The externally induced structural interconversions resulted in time-dependent fluorescence changes. This allowed sets of privileged number array codes to be generated.

Visualizing Drug Release from a Stimuli-Responsive Soft Material Based on Amine-Thiol Displacement.

In this research, we developed a photoluminescent platform using amine-coupled fluorophores, generated from a single conjugate acceptor containing bis-vinylogous thioesters. Based on the experimental and computational results, the fluorescence turn-on mechanism was proposed to be charge separated induced energy radiative transition for the amine-coupled fluorophore, while the sulfur-containing precursor was not fluorescent since the energy internal conversion occurred through vibrational 2RS- (R represents alkyl groups) as energy acceptor(s). Further utilizing the conjugate acceptor, we establish a new fluorogenic approach via a highly cross-linked soft material to selectively detect cysteine under neutral aqueous conditions. Turn-on fluorescence emission and macroscopic degradation occurred in the presence of cysteine as the stimuli, which can be visually tracked due to the generation of an optical indicator and the cleavage of linkers within the matrix. Furthermore, a novel drug delivery system was constructed, achieving controlled release of sulfhydryl drug (6-mercaptopurine) which was tracked by photoluminescence and high-performance liquid chromatography. The photoluminescent molecules developed herein are suitable for visualizing polymeric degradation, making them suitable for additional "smart" material applications.

Acid-Resistant BODIPY Amino Acids for Peptide-Based Fluorescence Imaging of GPR54 Receptors in Pancreatic Islets.

The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited fluorescent probes or antibodies for direct imaging of these receptors in cells and intact tissues, which can help to interrogate their multiple biological roles. Herein, we describe the rational design and characterization of a new acid-resistant BODIPY-based amino acid (Trp-BODIPY PLUS), and its implementation for solid-phase synthesis of fluorescent bioactive peptides. Trp-BODIPY PLUS retains the binding capabilities of both short linear and cyclic peptides and displays notable turn-on fluorescence emission upon target binding for wash-free imaging. Finally, we employed Trp-BODIPY PLUS to prepare some of the first fluorogenic kisspeptin-based probes and visualized the expression and localization of GPR54 receptors in human cells and in whole mouse pancreatic islets by fluorescence imaging.

Acid-Resistant BODIPY Amino Acids for Peptide-Based Fluorescence Imaging of GPR54 Receptors in Pancreatic Islets.

The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited fluorescent probes or antibodies for direct imaging of these receptors in cells and intact tissues, which can help to interrogate their multiple biological roles. Herein, we describe the rational design and characterization of a new acid-resistant BODIPY-based amino acid (Trp-BODIPY PLUS), and its implementation for solid-phase synthesis of fluorescent bioactive peptides. Trp-BODIPY PLUS retains the binding capabilities of both short linear and cyclic peptides and displays notable turn-on fluorescence emission upon target binding for wash-free imaging. Finally, we employed Trp-BODIPY PLUS to prepare some of the first fluorogenic kisspeptin-based probes and visualized the expression and localization of GPR54 receptors in human cells and in whole mouse pancreatic islets by fluorescence imaging.

Targeting Oncogene Promoters and Ribosomal RNA Biogenesis by G-Quadruplex Binding Ligands Translate to Anticancer Activity.

G-Quadruplex (GQ) nucleic acids are promising therapeutic targets in anticancer research due to their structural robustness, polymorphism, and gene-regulatory functions. Here, we presented the structure-activity relationship of carbazole-based monocyanine ligands using region-specific functionalization with benzothiazole (TCA and TCZ), lepidine (LCA and LCZ), and quinaldine (QCA and QCZ) acceptor moieties and evaluated their binding profiles with different oncogenic GQs. Their differential turn-on fluorescence emission upon GQ binding confirmed the GQ-to-duplex selectivity of all carbazole ligands, while the isothermal titration calorimetry results showed selective interactions of TCZ and TCA to c-MYC and BCL-2 GQs, respectively. The aldehyde group in TCA favors stacking interactions with the tetrad of BCL-2 GQ, whereas TCZ provides selective groove interactions with c-MYC GQ. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) showed that these molecules interfere with the recruitment of specific transcription factors at c-MYC and BCL-2 promoters and stabilize the promoter GQ structures to inhibit their constitutive transcription in cancer cells. Their intrinsic turn-on fluorescence response with longer lifetimes upon GQ binding allowed real-time visualization of GQ structures at subcellular compartments. Confocal microscopy revealed the uptake of these ligands in the nucleoli, resulting in nucleolar stress. ChIP studies further confirmed the inhibition of Nucleolin occupancy at multiple GQ-enriched regions of ribosomal DNA (rDNA) promoters, which arrested rRNA biogenesis. Therefore, carbazole ligands act as the "double-edged swords" to arrest c-MYC and BCL-2 overexpression as well as rRNA biogenesis, triggering synergistic inhibition of multiple oncogenic pathways and apoptosis in cancer cells.

Sensing Properties of NH2-MIL-101 Series for Specific Amino Acids via Turn-On Fluorescence.

Metal–organic frameworks (MOFs) have been demonstrated to be desired candidates for sensing definite species owing to their tunable composition, framework structure and functionality. In this work, the NH2-MIL-101 series was utilized for sensing specific amino acids. The results show that cysteine (Cys) can significantly enhance the fluorescence emission of NH2-MIL-101-Fe suspended in water, while NH2-MIL-101-Al exhibits the ability to sense lysine (Lys), arginine (Arg) and histidine (His) in aqueous media via turn-on fluorescence emission. Titration experiments ensure that NH2-MIL-101-Fe and NH2-MIL-101-Al can selectively and quantitatively detect these amino acids. The sensing mechanism was examined and discussed. The results of this study show that the metal centers in MOFs are crucial for sensing specific amino acids.

Deciphering the Chemical Basis of Fluorescence of a Selenium-Labeled Uracil Probe when Bound at the Bacterial Ribosomal A-Site.

We unveil in this work the main factors that govern the turn-on/off fluorescence of a Se-modified uracil probe at the ribosomal RNA A-site. Whereas the constraint into an "in-plane" conformation of the two rings of the fluorophore is the main driver for the observed turn-on fluorescence emission in the presence of the antibiotic paromomycin, the electrostatics of the environment plays a minor role during the emission process. Our computational strategy clearly indicates that, in the absence of paromomycin, the probe prefers conformations that show a dark S1 electronic state with participation of nπ* electronic transition contributions between the selenium atom and the π-system of the uracil moiety.

Recyclable macromolecular thermogels for Hg(II) detection and separation via sol-gel transition in complex aqueous environments

The sensitive detection and quantitative separation of toxic heavy metal ions in aqueous media are of great importance. In this study, a thermogelling poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) triblock copolymer (P1) was synthesized, and difluoroboron dipyrromethene (BODIPY) fluorophore integrated with thiosemicarbazide units was attached to the chain ends of P1 through consecutive post-polymerization modifications, leading to P4. P4 exhibited rapid and selective detection of Hg(II) in 100% aqueous media via turn-on fluorescence emission with a limit of detection (LOD) of as low as 0.461 μM. This turn-on emission behavior is attributed to the suppression of C˭N isomerization caused by the formation of a coordination complex between P4 and Hg(II) ions. The selective and quantitative removal of Hg(II) among various metal ions was achieved by trapping chelated Hg(II) ions inside the dehydrated P4 gel via thermo-controlled sol-gel-dehydrated gel transitions. Treating the Hg(II) ion-trapped dehydrated gels with sodium sulfide (Na2S) in acetone/water at room temperature led to HgS precipitates, and P4 in solution was dried and recycled. This recyclable thermoresponsive macromolecular probe is promising for not only Hg(II) detection but also its separation and removal from complex aqueous environments.

Anion-binding-induced and reduced fluorescence emission (ABIFE & ABRFE): A fluorescent chemo sensor for selective turn-on/off detection of cyanide and fluoride.

A new hydrazine based π-hole assisted, electron deficient turn-on/off fluorescent and colorimetric sensor L with anion-binding induced/reduced fluorescent emission (ABIFE & ABRFE) has been designed and synthesized. The prepared sensor L exhibited excellent turn-on fluorescence emission in the presence of cyanide ion through ABIFE. On the other hand, the receptor L turns-off its fluorescence intensity upon binding with fluoride; however, the reduced emission intensity of this complex of L is recovered by addition of cyanide. The sensor L is almost intact with other tested anions. To the best of our knowledge, this is the first report on sensing of cyanide and fluoride by a neutral hydrazine based receptor via anion-binding-induced fluorescence emission (ABIFE) and anion-binding-reduced fluorescence emission (ABRFE) mechanisms respectively. The observed ABIFE and ABRFE phenomena of L with cyanide is further supported by UV-Vis, Emission, 1H NMR and IR spectroscopic studies.

Macrocyclic “tet a” derived colorimetric sensor for the detection of mercury cations and hydrogen sulphate anions and its bio-imaging in living cells

A mono-N-substituted probe L containing a bromosalicylaldehyde pendant arm attached to a tetraazamacrocyclic “tet a” moiety was synthesized via straight forward reaction. The probe L crystallizes in a monoclinic P21/n space group. The probe L displayed quick sensitivity and selectivity towards Hg2+ ions due to its hopeful Chelation Enhancement Quenching (CHEQ) feature. Interestingly, the probe L exhibits turn-off fluorescence response to Hg2+ ion and turn-on fluorescence signals to HSO4− ions. When the probe L was complexed with HSO4− in 1:1 mode (L + HSO4− formation), improved turn-on fluorescence emission was detected due to the chelation enhanced fluorescence effect through sensor complex. The macrocyclic “tet a” probe L exhibited a binding constant value of 3.89 × 106 M−1 and 5.58 × 105 M−1 for Hg2+ and HSO4−, respectively. Probe L exhibited good selectivity to Hg2+ rather than other common metal ions and HSO4− over other common anions. The limit of detection (LOD) of Hg2+ and HSO4− were found to be 1 nM and 7 μM, respectively. The time-resolved fluorescence emission single-photon counting study was used to determine the average lifetime value for the probe L and L + HSO4− ions as 0.47 and 1.02 ns, respectively. The practical application of the probe in visualizing intracellular Hg2+ and HSO4− ions distribution in live Artemia salina was demonstrated. Furthermore, the probe L with Hg2+cations was found to be cytotoxic against breast cancer cells in nature and can be delivered as an anticancer agent. Besides the probe L with HSO4− exhibit strong fluorescence emission with low cytotoxicity, and it can be recommended for live-cell imaging.

A phenoxazine-based fluorescent chemosensor for dual channel detection of Cd2+ and CN− ions and its application to bio-imaging in live cells and zebrafish

A simple phenoxazine-based fluorescence chemosensor N-(4-((4-((5-oxo-5H-benzo [a]phenoxazin-6-yl)amino)phenyl)sulfonyl)phenyl)furan-2-carboxamide (NPC) was developed for discriminative detection of Cd2+ and CN− ions. This easily available chemosensor was synthesized by adding a furan-2-carboxamide group to a phenoxazine fluorophore and a phenyl sulfonyl chelating site. The sensor NPC exhibited turn-on fluorescence emission for Cd2+, and the obtained NPC–Cd2+ complex detected CN−via turn-off fluorescence response with 2:1 binding stoichiometry in CH3CN/H2O (99:1 v/v) medium by fluorescence spectroscopy. The detection limits of Cd2+ and CN− were 0.60 μM and 0.145 μM, respectively, which were significantly lower than the World Health Organization guidelines. The proposed mechanism of sensor NPC was additionally supported by NMR, FT-IR analyses, DFT and a UV/visible titration studies. Furthermore, the sensor NPC has been successfully demonstrated as a biomarker for detecting Cd2+ in live cells and zebrafish larvae.

Efficient cell surface labelling of live zebrafish embryos: wash-free fluorescence imaging for cellular dynamics tracking and nanotoxicity evaluation.

Imaging the dynamics and behaviors of plasma membranes is at the leading edge of life science research. We report here the development of a universal red-fluorescent probe Chol-PEG-Cy5 for wash-free plasma membrane labelling both in vitro and in vivo. In aqueous solutions, the fluorescence of Chol-PEG-Cy5 is significantly quenched due to the intermolecular resonance energy transfer (RET) between neighbouring Cy5 moieties; however, upon membrane anchoring, the probes undergo lateral diffusion in lipid bilayers, resulting in weakened RET and turn-on fluorescence emission. We demonstrate that Chol-PEG-Cy5 enables rapid, stable and high-quality in vitro cell surface imaging in a variety of mammalian cells. Additionally, with the assistance of three-dimensional (3D) image reconstruction, we achieve for the first time the whole-mount in situ fluorescence imaging of the epidermal cell surfaces of live zebrafish embryos, which cannot be realized by conventional plasma membrane probes due to the presence of the surface-covering mucus barrier. This novel technique encourages us to track the cellular dynamics of the epidermis during embryonic development with 3D visualization. Moreover, we also develop a new method to evaluate the epidermal toxicity of nanomaterials (e.g., gold nanoparticles and graphene oxide nanosheets) toward zebrafish embryos using this fluorescent probe.

High Performance Fluorescent Turn-On Probe for Amitriptyline Based on Hybrid Nanoassembly of Organic-Inorganic Nanoparticles.

Fluorescence methods have gained enormous attention due to their ease in use, simplicity, selectivity and sensitivity. Fluorescent chemosensors respond instantly by converting molecular recognition to fluorescent signals. The consumption of pharmaceutical products by living beings is on great increase. The disposal of such compounds in the environment is a matter of great concern as these compounds enter aquatic environment and show accumulation in tissues of aquatic organisms. In the present study, we have utilized naphthalimide based receptors to fabricate organic nanoparticles (ONPs). These ONPs were used for the development of hybrid nanoassemblies, and the developed nanoassemblies were characterized with the help of transmission electron microscopy and dynamic light scattering studies. The photophysical studies were performed and the hybrid assembly developed using receptor 2 demonstrated a turn-on fluorescence emission behavior on binding with Amitriptyline. The present sensing system acted as promising candidate for determination of Amitriptyline among other contending drug molecules. The established system can recognize Amitriptyline up to a detection limit of 48 nM in aqueous medium. Electrochemical recognition studies show binding of hybrid nanoassembly of receptor 2 with Amitriptyline with limit of detection of 21 nM.

Programmable Metal/Semiconductor Nanostructures for mRNA-Modulated Molecular Delivery.

Cytotoxic chemotherapeutics are important tools for the clinical treatment of a variety of solid tumors. However, their use is often complicated by multidrug resistance that can develop in patients, limiting the potencies of these agents. New strategies are needed to provide versatile systems that can respond to and disable resistance mechanisms. We demonstrate the use of a new family of materials, programmable metal/semiconductor nanostructures, for drug delivery and mRNA sensing in drug-resistant cells. These materials are composed of a central core gold nanoparticle surrounded by a layer of DNA-capped quantum dots. The modularity of these "core-satellite" assemblies allows for the construction of superstructures with controlled size and the incorporation of multiple functionalities for drug delivery. The DNA sequence within the nanoparticle specifically binds to an mRNA encoding an important drug resistance factor, MRP1, inside cancer cells, releasing a potent anticancer drug doxorubicin. This event triggers a turn-on fluorescence emission along with a downregulation of the MRP1 drug efflux pump, a main resistance factor for doxorubicin, yielding a remarkable improvement in therapeutic efficacy against drug-resistant cancer cells. This work paves the way for the development of programmable materials with multiple synergistic functionalities for biomedical applications.

Phenothiazine Based Donor-Acceptor Compounds with Solid-State Emission in the Yellow to NIR Region and Their Highly Selective and Sensitive Detection of Cyanide Ion in ppb Level.

Four new novel donor-acceptor (A-π-D-A, A-D-π-D-A) compounds (1 a, 1 b, 2 a and 2 b) based on ethylenedioxythiophene (EDOT) and phenothiazine (PTz) have been rationally designed and synthesized towards solid state emission ranging from yellow to near infrared (NIR). The compounds 1 b and 2 b, in thin film form, showed an emission maximum at 713 nm and 696 nm, respectively, with the corresponding absolute solid-state quantum yield of 3.3 % and 9.0 %. The fluorophores showed high emission in the doped state as well when dispersed in polystyrene (PS) matrix with emission maximum ranging from 536 nm to 648 nm with quantum yield in the range 12.4 %-64.4 %. The presence of dicyanovinyl (DCV) group in both the fluorophores was exploited towards cyanide sensing in DMSO leading to turn-on fluorescence emission with high selectivity and sensitivity for cyanide ion with a detection limit of as low as 0.32 μm (8 ppb) for 1 b and 0.57 μm (14 ppb) for 2 b. DFT and TTDFT calculations suggested that the addition of cyanide ion prevented the intramolecular charge transfer (ICT) from the donor (PTz or EDOT) to acceptor (DCV), thereby turning the fluorescence "On". Using fluorescent spectral and color switching, we have explored logic gates with single and two input signal amplification by applying chemical and light inputs in the form of CN- ion and UV.

A heptamethine cyanine dye with turn-on fluorescence emission for mitochondria-targeting and photothermal therapy

A heptamethine cyanine dye with turn-on fluorescence emission for mitochondria-targeting and photothermal therapy

A cancer cell turn-on protein-CuSMn nanoparticle as the sensor of breast cancer cell and CH3O-PEG-phosphatide

Cancer activated protein-inorganic nanoparticles can be cancer targeting turn-on imaging and therapy agents. Although various techniques were successfully employed for development of hybrid protein-inorganic nanoparticles, cancer cell activated protein-inorganic nanoparticles have been challengeable. Herein, a cancer cell responsive nanoparticle (PDAMn-CuS@BSA-FA, NPs) was constructed and characterized. It is found that the quenching interaction of dyes (PDA) and central metal in NPs can be adjusted by CH3O-PEG-phosphatide or the cancer cells, hence, NPs showed turn-on fluorescence emission with the titration of CH3O-PEG-phosphatide. In particular, breast cancer cells lysis can switch on the green emission greatly, while normal cells show less effect. Breast cancer cells turn-on fluorescence imaging and mitochondria targeting imaging demonstrate that the NPs can sense breast cancer cells and enter mitochondria. Therefore, NPs can be both breast cancer targeting nanosensor.

A fluorescence turn-on probe based on rhodamine derivative and its functionalized silica material for Hg2+-selective detection

In current study, a novel optical probe based on rhodamine-terephthalaldehyde Schiff base was developed for exclusive detection of Hg2+ in 9:1 (v/v) ethanol/water solution, which exhibited obvious turn-on fluorescence emission when encountering Hg2+, and distinct color change from colorless to violet also enabled “naked eye” detection due to spirolactam opening of this rhodamine sensing molecule. Other common ions including alkali ions (Na+, K+) and alkaline earth metal ions(Ca2+, Mg2+) together with some transition metal ions (Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Ag+, Pb2+, Cr3+, Fe3+) could only induce negligible spectral changes. Furthermore, our probe was successfully grafted onto the surface of silica nanoparticles to guarantee sensing repeatability and explore its further applications in optical sensing devices. It turned out that, the inorganic–organic hybrid materials also exhibited excellent recognition ability to Hg2+.