Blue Fluorophore Research Articles

Ionic fluorescent sensor targeting receptor tyrosine kinases for biosystems imaging and application in flow cytometry

Fluorescent imaging of receptor tyrosine kinases in living biosystems is an important means for the early diagnosis of cancer, herein an ionic fluorescent sensor (SNB) composed of targeting unit (sunitinib) and nile blue fluorophore linked via long flexible chain has been designed and evaluated. The SNB sensor exhibits distinct fluorescence responses to receptor tyrosine kinases derived from unfolding strategy and targeting ability, which were evaluated through 2D NMR analyses, optical studies, kinase activity assays. The SNB sensor has excellent membrane fluorescent imaging by electrostatic adsorption and can selectively insert into receptor tyrosine kinases domain pocket on the membrane of cancer cell lines. The SNB sensor has been successfully applied in flow cytometry for cell sorting and fluorescence imaging with tumor mouse model in vivo. The SNB senor may help transition the technology into a widely suitable tool for flow cytometry, imaging with confocal microscopes, whole animal imaging and possibly facilitating early diagnoses and treatment of cancer.

Highly efficient nondoped blue organic light-emitting diodes based on a star-group tetraphenylethylene-substituted aggregation-induced-emission-active organic fluorescent small molecules

Tetraphenylethene (TPE) is a star group exhibiting an excellent aggregation-induced emission (AIE) effect. Although significant progress has been made in the field of organic electroluminescence (EL) based on TPE-substituted emitters, highly efficient and high-color-purity TPE-substituted blue fluorophores with the AIE effect are still very rare. In this paper, a simple and effective molecule—N-phenyl-N-(4-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)phenyl)-4′-(1,2,2-triphenylvinyl)-[1,1′-biphenyl]-4-amine (TPETPAPI)—was designed and synthesized using triphenylamine (donor), phenanthroimidazole (acceptor), and tetraphenylethylene (AIE generator). In tetrahydrofuran solution, the molecule emits little light and the quantum efficiency is low (1.3%); however, the fluorescence is enhanced in the film (73%), exhibiting remarkable AIE properties, thus enabling TPETPAPI to be used in future applications in organic light-emitting diodes. The nondoped device exhibits a low turn-on voltage of 3.0 V, a maximum luminance of 10780 cd m−2, maximum current efficiency of 12.20 cd A−1, and maximum power efficiency of 11.95 lm W−1, with an EL peak at 476 nm. TPETPAPI exhibits the most impressive EL performance reported to date for a TPE-substituted blue fluorophore with AIE' characteristics.

Aggregation-Induced Energy Transfer in Color-Tunable Multiblock Bottlebrush Nanofibers.

The synthesis of multicomponent nanoscale structures with precisely addressable function is critical to the discovery of both new phenomena and new applications in nanotechnology. Though self-assembly offers low-cost routes to many such materials, these methods often require building blocks with particular structural motifs, thus limiting the scope of nanomaterials that can be prepared in these ways. Herein we use a bottom-up approach based on covalent chemistry to synthesize a series of bottlebrush copolymers from red, green, and blue luminescent macromonomers, which were then used to prepare multiblock organic nanofibers structurally analogous to nanoscale RGB pixels. Efficient energy transfer from a blue fluorophore to red and green phosphors can be modulated, using the solvent polarity as a stimulus, to give aggregation-induced changes in emission color. Aggregation was also accompanied by changes in the emission lifetime of the nanofiber from the nanosecond to microsecond regime. Additionally, changes in energy transfer efficiency and interchromophore distance were quantified using a FRET model. Preliminary demonstration of these materials as polarity-sensitive inks for encryption and encoding were also demonstrated using a red/blue fluorescence switch upon exposure to solvent. Finally, the potential complexity of optoelectronic materials accessible with these methods was demonstrated by combining these building blocks with charge-transporting materials to give organic nanofibers with ordered structures mimicking that of multilayer white OLEDs. Ultimately this work describes the preparation of robust, multicomponent nanofibers from general building blocks, combining their optoelectronic properties in ways that can be both reversibly switched and temporally resolved.

High-efficiency and low efficiency roll-off in white organic light-emitting diodes employing a novel blue emitter

Abstract A novel blue fluorophore of 3,40-bis(1-phenyl-phenanthro[9,10-d]-imidazol-2-yl) biphenyl (L-BPPI) was firstly utilized as the blue fluorescent emitter to fabricate highly efficient fluorescent/phosphorescent hybrid white organic light-emitting diodes (WOLEDs). By introducing a mixed interlayer between the blue fluorescent and orange phosphorescent region, two-color WOLED exhibited CIE coordinates close to the equal energy point of (0.33, 0.33) with peak efficiencies of 40.7 cd/A and 26.8 lm/W. And fairly stable white emission spectra were realized owing to the well control of exciton distribution and charge transport balance. Moreover, three-color WOLED was achieved when an ultrathin red phosphorescent emitter was inserted. The result device with reduced efficiency roll-off showed peak efficiencies of 35.3 cd/A and 25.4 lm/W.

Efficient Orange-Red Thermally Activated Delayed Fluorescence Emitters Feasible for Both Thermal Evaporation and Solution Process.

Development of red thermally activated delayed fluorescence (TADF) emitters has been lagging behind when compared with those of blue and green fluorophores, especially for solution-processable ones. In this work, two novel orange-red TADF emitters 3,6-di(10H-phenoxazin-10-yl)dibenzo[a,c]phenazine (DBPZ-DPXZ) and 10,10'-(11,12-bis(3,5-di-tert-butylphenyl)dibenzo[a,c]phenazine-3,6-diyl)bis(10H-phenoxazine) (tDBBPZ-DPXZ) are developed. A high-performance orange-red TADF emitter, DBPZ-DPXZ, is first prepared by connecting a rigid acceptor and two rigid donor segments. While this design strategy endows DBPZ-DPXZ with an excellent TADF performance leading to a vacuum-processed organic light-emitting diode (OLED) with a high external quantum efficiency (EQE) of 17.8%, the rigid segments limit its solubility and applications in solution-processed devices. Based on this prototype, tDBBPZ-DPXZ is designed with the addition of 3,5-di-tert-butylphenyl groups to boost its solubility with barely an influence on the photophysical properties. In particular, tDBBPZ-DPXZ maintains nearly an identical photoluminescence quantum yield of 83% and singlet-triplet energy splitting of 0.03 eV with EQE of 17.0% in a vacuum-processed orange-red OLED. Furthermore, it can be applied on the orange-red solution-processed OLED realizing an EQE as high as 10.1%, representing one of the state-of-the-art results of the reported orange-red solution-processed TADF-OLEDs. This work provides an effective strategy to address the conflicting requirements between high efficiency and good solubility and develop efficient soluble orange-red TADF emitters.

Fluorophore-Dependent Cleavage of Disulfide Bond Leading to a Highly Selective Fluorescent Probe of Thioredoxin.

Finding specific small molecule probes of a biological target is extremely desired but remains a big challenge. We reported herein a highly selective fluorescent probe derivatized from the nile blue fluorophore, NBL-SS, for thioredoxin (Trx), a ubiquitous redox-regulating protein essentially involved in cell growth, differentiation, and death. NBL-SS displayed multiple favorable properties, such as red emission, fast response, and high fluorescence signal, which enabled the probe to readily image Trx functions in live cells and in vivo. The fluorophore-dependent selectivity indicates that manipulation of weak interactions between probes and their target biomacromolecules could further improve the probes' specificity. In addition, our discovery, i.e., the preference reduction of simple disulfide bonds by Trx over glutathione, also advances the development of disulfide cleavage-based probes, prodrugs, and theranostic agents.

Fluoroquinolone-derived fluorescent probes for studies of bacterial penetration and efflux.

Fluorescent probes derived from the fluoroquinolone antibiotic ciprofloxacin were synthesised using a Cu(i)-catalysed azide-alkyne cycloaddition (CuAAC) to link a ciprofloxacin azide derivative with alkyne-substituted green and blue fluorophores. The azide (2) and fluorophore (3 and 4) derivatives retained antimicrobial activity against Gram-positive and Gram-negative bacteria. The use of confocal fluorescent microscopy showed intracellular penetration, which was substantially enhanced in the presence of carbonyl cyanide 3-chlorophenylhydrazone as an efflux pump inhibitor in Escherichia coli.

A novel D–π–A blue fluorophore based on [1,2,4]triazolo[1,5-a]pyridine as an electron acceptor and its application in organic light-emitting diodes

A novel luminophore based on [1,2,4]triazolo[1,5-a]pyridine has been utilized as an emitter and host for high-efficiency deep-blue fluorescence and orange phosphorescence OLEDs, respectively.

Synthesis and application of the blue fluorescent amino acid l-4-cyanotryptophan to assess peptide-membrane interactions.

Recently, l-4-cyanotryptophan has been shown to be an efficient blue fluorescence emitter, with the potential to enable novel applications in biological spectroscopy and microscopy. However, lack of facile synthetic routes to this unnatural amino acid limits its wide use. Herein, we describe an expedient approach to synthesize Fmoc protected l-4-cyanotryptophan with high optical purity (>99%). Additionally, we test the utility of this blue fluorophore in imaging cell-membrane-bound peptides and in determining peptide-membrane binding constants.

Spiropyran-Based Nanocarrier: A New Zn2+ -Responsive Delivery System with Real-Time Intracellular Sensing Capabilities.

A new spiropyran-based stimuli-responsive delivery system is fabricated. It encapsulates and then releases an extraneous compound in response to elevated levels of Zn2+ , a critical factor in cell apoptosis. A C12 -alkyl substituent on the spiropyran promotes self-assembly into a micelle-like nanocarrier in aqueous media, with nanoprecipitation and encapsulation of added payload. Zn2+ binding occurs to an appended bis(2-pyridylmethyl)amine group at biologically relevant micromolar concentration. This leads to switching of the spiropyran (SP) isomer to the strongly fluorescent ring opened merocyanine-Zn2+ (MC-Zn2+ ) complex, with associated expansion of the nanocarriers to release the encapsulated payload. Payload release is demonstrated in solution and in HEK293 cells by encapsulation of a blue fluorophore, 7-hydroxycoumarin, and monitoring its release using fluorescence spectroscopy and microscopy. Furthermore, the use of the nanocarriers to deliver a caspase inhibitor, Azure B, into apoptotic cells in response to an elevated Zn2+ concentration is demonstrated. This then inhibits intracellular caspase activity, as evidenced by confocal microscopy and in real-time by time-lapsed microscopy. Finally, the nanocarriers are shown to release an encapsulated proteasome inhibitor (5) in Zn2+ -treated breast carcinoma cell line models. This then inhibits intracellular proteasome and induces cytotoxicity to the carcinoma cells.

Blue-Light-Emitting Photostable Hybrid Films for High-Efficiency Large-Area Light Converter and Photonic Applications.

A blue fluorophore of Schiff base zinc complex is prepared by a hydrolysis-free solution-based synthetic method. Under ultraviolet (UV) excitation, the complex produces blue emission with a quantum yield ( Q) of 42.6% in methylene chloride and 24.0% in standalone powder form. Quantum mechanical calculations show that the blue emission is generated by the change in the chemical state of the ligand associated with the complexation with Zn cations. Thin films of Zn complexes incorporated in polymethylmethacrylate (PMMA) and cellulose acetate butyrate (CAB) polymers are also prepared by dispersing the complexes into the polymer matrices. These hybrid polymer films exhibit several notable features, particularly enhanced luminescence efficiency (with maximum Q of 85.8% for PMMA and 30.0% for CAB) and scalability for fabrication over a large area while retaining the original properties of the host polymers. Light-emitting diodes are also fabricated using the CAB hybrid thin films, and they show a Q of 43.2% with excellent photostability. The complex and its hybrid films demonstrate their great potential for such applications as UV-to-blue conversion devices in photoelectronics, solar-cell concentrators, solid-state lighting and display, and greenhouse agriculture.

Aminopeptidase‐N‐activated Theranostic Prodrug for NIR Tracking of Local Tumor Chemotherapy

AbstractThe development of molecular theranostic prodrugs for in vivo cancer diagnosis and targeted chemotherapy is urgently required. Enzyme‐activated prodrugs display superior selectivity as a result of cancer‐specific enzymes which serve as cancer biomarkers. Herein, an aminopeptidase N (APN)‐activated theranostic prodrug Nile blue‐C6‐amide‐p‐fluorophenylalanyl‐l‐melphalanyl (NBFMel) is reported for fluorescence cancer diagnosis and local tumor treatment. NBFMel demonstrates negligible cytotoxicity and very weak fluorescence due to the photoinduced electron transfer (PET) between melphalan and Nile blue fluorophore. After activation caused by APN, the prodrug releases free melphalan that inhibits tumor cell growth. Simultaneously, the reaction blocks the PET process and switches on the fluorescence, which can be used for cancer diagnosis. NBFMel is successfully utilized to report the presence of tumor and for in situ tracking of drug release in tumor‐bearing mouse models. Moreover, NBFMel demonstrates efficient tumor inhibition when intravenously injected into mice. Therefore, the APN‐activated theranostic prodrug provides a new platform for in vivo cancer diagnosis and targeted anticancer chemotherapy.

Synthesis, photophysical, theoretical and electroluminescence study of triphenylamine-imidazole based blue fluorophores for solution-processed organic light emitting diodes

The deep blue organic light emitting diodes (OLEDs) are necessary for solid-state lighting (SSL) and flat panel displays. In the practical application of OLEDs, high efficiencies and luminance with simple device structure, are highly desirable. Hence, we have designed and synthesized three blue (Donor-Acceptor) fluorophores with linear, bent and star-shaped molecular geometry by incorporating triphenylamine (TPA) as a hole transporting unit and imidazole as an electron transporting unite with electron withdrawing Ph-CF3 moiety at the N1 position of imidazole unit. The synthesized fluorophores were structurally characterized by Nuclear Magnetic Resonance Spectroscopy (NMR) and Mass spectroscopy. The linear-shaped fluorophore structurally characterized by single crystal X-ray diffraction. Photophysical, electrochemical and electronic (theoretical) properties of the synthesized fluorophores were systematically investigated. All the fluorophores are showing deep blue emission in DCM solution. The synthesized fluorophores are shown good quantum yield (Φ) in solution and solid phase. The structurally simple OLEDs devices were fabricated by using these fluorophores as emitters. All the fluorophores showed deep blue electroluminescence (EL) emission with good device efficiency. Among all the devices, based on TBIMTPA with a 5 wt % dopant concentration exhibited better performance in the series with a maximum luminance of 994 cd/m2, a current efficiency of 2.6 cd/A, a power efficiency of 1.0 lm/W and an EQE of 3.2% at brightness of 100 cd/m2. These results indicate that the introduction of imidazole-based accepter on the TPA core is a favorable design strategy towards deep blue emitters.

High-efficiency and color-stable warm white organic light-emitting diodes utilizing energy transfer from interface exciplex

Abstract We demonstrate high-efficiency warm white organic light-emitting diodes (WOLEDs) with an interface-exciplex-forming structure of hole-transporting 1,3-Bis(carbazol-9-yl)benzene (mCP) as electron-donor and electron-transporting 4,6-Bis(3,5-di(pyridin-3-yl)phenyl)-2-(pyridin-3-yl)pyrimidine (B3PyMPM) as electron-acceptor. The exciplex can be formed effectively at the interface of mCP/B3PyMPM due to the excellent charge-transporting properties of mCP and B3PyMPM and the large energy-levels offset of mCP/B3PyMPM interface, and then its energy transfers to the low-lying triplet states of the blue TADF fluorophors or yellow phosphors. As a result, a maximum power efficiency (PE) of 79.2 lm/W and maximum external quantum efficiency (EQE) of 22.3% were achieved from the warm WOLED. The key factor for such high efficiency WOLED is believed to be from the effective harvest of triplet excitons of the interface-exciplex via reverse intersystem crossing process (RISC).

Vapochromic polyketone films based on aggregation‐induced enhanced emission

Aliphatic polyketone (PK) films physically mixed with moderate amounts (0.6 wt%) of 4,4′‐bis(2‐benzoxazolyl)stilbene (BBS) fluorophores were demonstrated to be sensitive to volatile organic compounds. Notably, BBS/PK blends were prepared by means of a continuous 1‐step extrusion process in a pilot‐scale twin screw extruder and compression molded followed by rapid quenching in liquid nitrogen to get thin films (thickness of 150 μm) containing molecularly dispersed blue emissive BBS fluorophores. The 0.6 wt% BBS/PK films demonstrated significant vapochromism when exposed to volatile organic compounds characterized by favorable interactions with the polymer matrix such as chloroform. Solvent absorption caused PK matrix plasticization, thus increasing BBS mobility and triggering the self‐associations of molecules into bluish green‐emissive excimers/aggregates thanks to the emersion of the typical band at 500 nm. This phenomenon preferentially involves the BBS/PK film layers close to the air‐contact surface without affecting the bulk characteristics of the PK matrix. The easy modulation of the luminescent properties of PK films by varying the supramolecular organization of BBS dispersed molecules by chemical perturbations, and the use of melt‐processing procedures suggests the use for the first time of aliphatic PK in the development of smart materials for sensing applications.

Evidence of glucuronidationof the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.

LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes. The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs). We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid. LW-1 was extracted and highly purified from ~99g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC). Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1. To confirm this data, LW-1 was incubated with β-glycosidases (glucosidase, galactosidase, glucuronidase) and products were analyzed by LC-MS. Only glucuronidase could cleave the sugar from the parent molecule. These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications". Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.

An effective and facile synthesis of new blue fluorophores on the basis of an 8-azapurine core.

A convenient synthesis of 2-aryl-2,4-dihydro-5H-[1,2,3]triazolo[4,5-d]pyrimidin-5-ones (DTPs) from 3,3-diamino-2-(arylazo)acrylonitriles through a versatile and readily accessible two-step procedure is described. Density functional theory (DFT) calculations were performed to explain the selectivity of the heterocyclization step, which predominantly afforded 6-amino-5-(arylazo)pyrimidin-2(1H)-thiones in chloroform or ethanol, and 2,3-dihydro-1,2,4-triazines in toluene or DMF. Novel 2-aryl-2,4-dihydro-5H-[1,2,3]triazolo[4,5-d]pyrimidin-5-ones were obtained in good yields and showed absorption in the ultraviolet region and good emission in the blue region. The photophysical properties of DTPs were better than those cited in select literature examples of 8-azapurines. Owing to the facile synthesis and good photophysical characteristics in an aqueous medium, the new DTPs should have potential applications as organic fluorophores in fluorescence imaging and materials science.

Blue Fluorescence from BF2 Complexes of N,O-Benzamide Ligands: Synthesis, Structure, and Photophysical Properties.

Small molecules having intense luminescence properties are required to promote biological and organic material applications. We prepared five types of benzamides having pyridine, pyridazine, pyrazine, and pyrimidine rings and successfully converted them into three types of the difluoroboronated complexes, Py@BAs, as novel blue fluorophores. Py@BA having a pyridine moiety (2-Py@BA) showed no fluorescence in solution, whereas Py@BAs of pyridazine and pyrazine moieties (2,3-Py@BA and 2,5-Py@BA, respectively) emitted blue fluorescence with quantum yields of ca. 0.1. Transient absorption measurements using laser flash photolysis of the Py@BAs revealed the triplet formation of 2,3- and 2,5-Py@BAs, while little transient signal was observed for 2-Py@BA. Therefore, the deactivation processes from the lowest excited singlet state of fluorescent 2,3- and 2,5-Py@BAs consist of fluorescence and intersystem crossing to the triplet state while that of the nonfluorescent Py@BA is governed almost entirely by internal conversion to the ground state. Conversely, in the solid state, 2-Py@BA emitted intense fluorescence with a fluorescence quantum yield as high as 0.66, whereas 2,3- and 2,5-Py@BAs showed fluorescence with quantum yields of ca. 0.2. The crystal structure of 2-Py@BA took a herringbone packing motif, whereas those for 2,3- and 2,5-Py@BAs were two-dimensional sheetlike. On the basis of the difference in crystal structures, the emission mechanism in the solid state was discussed.

Solution‐Processable Thermally Activated Delayed Fluorescence White OLEDs Based on Dual‐Emission Polymers with Tunable Emission Colors and Aggregation‐Enhanced Emission Properties

AbstractThermally activated delayed fluorescence (TADF) white organic light‐emitting diodes (WOLEDs) have drawn tremendous interest and have been extensively studied because of harvesting both triplet and singlet excitons without heavy metals. However, single white‐light‐emitting polymers are currently limited and few strategies exist to design these materials. Herein, a new strategy is proposed to develop the polymers with tunable emission colors by combining fluorescence and TADF based on aggregation‐enhanced emission (AEE) characteristics. The polymers containing different ratios of pendant 2‐(10H‐phenothiazin‐10‐yl)dibenzothiophene‐S,S‐dioxide units with yellow TADF emission and dibenzothiophene units with blue fluorophor emission, which display both TADF and AEE characteristics, are synthesized successfully. Among them, the emission color of P3 in different tetrahydrofuran/water mixtures changes from greenish‐blue to white or yellow. Moreover, P3 displays white emission in the solid state dispersing by poly(methyl methacrylate). In addition, electroluminescent device of P3 achieve white light emission with high color rending indexes (CRI) and low turn‐on voltages (V on ). P3 OLEDs show two‐color warm‐white emission with high CRI of 77, low V on of 2.9 V, CEmax of 23.0 cd A−1, PEmax of 32.8 lm W−1, external quantum efficiency (EQE)max of 10.4% with Commission Internationale de l'Eclairage coordinates of (0.37, 0.38) at 5 V. Moreover, EQE of 2.6%, CE of 5.7 cd/A, PE of 4.7 lm W−1 at 100 cd m−2 are obtained. To the best of our knowledge, this work reports the first example of warm‐white TADF polymer OLEDs.

Evaluation of antioxidants and argpyrimidine in normal and cataractous lenses in north Indian population.

To assess the level of glutathione, thioltransferase, and argpyrimidine in nuclear and cortical cataractous lenses as well as in the clear lenses in the north Indian population. Human cataractous lenses were collected from the patients who underwent extracapsular cataract extraction surgery; clear lenses were collected from the freshly donated eye bank eyes. Antioxidant molecules such as glutathione and thioltransferase enzyme activity were measured; simultaneously in these lenses a blue fluorophore argpyrimidine, an advanced glycation end (AGE) product level was assessed using high performance liquid chromatography (HPLC). The protein concentration was found to be present at higher levels in the control lenses compared to cataract lenses. A significant decrease in the glutathione level was observed in the nuclear cataractous lenses compared to cortical cataractous (P=0.004) and clear lenses (P≤0.005), but no significant change in the level of antioxidant enzyme thioltransferase was observed. Further, argpyrimidine a blue fluorophore (AGE) was found to be significantly higher in the nuclear cataract (P=0.013) compared to cortical cataract lenses. Antioxidants such as glutathione significantly decrease in age-related nuclear and cortical cataract and an AGE, argpyrimidine are present at significantly higher levels in nuclear cataract.