A Water-Soluble Wavy Coordination Polymer of Cu(II) as a Turn-On Luminescent Probe for Histidine and Histidine-Rich Proteins/Peptides.

Histidine plays an essential role in most biological systems. Changes in the homeostasis of histidine and histidine-rich proteins are connected to several diseases. Herein, we report a water-soluble Cu(II) coordination polymer, labeled CuCP, for the fluorimetric detection of histidine and histidine-rich proteins and peptides. Single-crystal structure determination of CuCP revealed a two-dimensional wavy network structure in which a carboxylate group connects the individual Cu(II) dimer unit in a syn-anti conformation. The weakly luminescent and water-soluble CuCP shows turn-on blue emission in the presence of histidine and histidine-rich peptides and proteins. The polymer can also stain histidine-rich proteins via gel electrophoresis. The limits of quantifications for histidine, glycine-histidine, serine-histidine, human serum albumin (HSA), bovine serum albumin, pepsin, trypsin, and lysozyme were found to be 300, 160, 600, 300, 600, 800, 120, and 290 nM, respectively. Utilizing the fluorescence turn-on property of CuCP, we measured HSA quantitatively in the urine samples. We also validated the present urinary HSA measurement assay with existing analytical techniques. Job's plot, 1H NMR, high-resolution mass spectrometry (HRMS), electron paramagnetic resonance (EPR), fluorescence, and UV-vis studies confirmed the ligand displacement from CuCP in the presence of histidine.

Microwave synthesized novel biomass carbon dots applied in the fluorescent detection of crystal violet.

To establish a new method for detecting crystal violet (CV), a harmful dye, herein, a genre of novel biomass carbon dots (CDs) was synthesized via a microwave method and employed as a fluorescent probe, in which water spinach and polyethylene glycol (PEG) performed as raw materials. Based on the inner filter effect (IFE) between the luminescent CDs and CV, the blue emission of this probe at 430 nm could be quenched by CV. Hence, a new strategy was proposed to selectively determine CV in aquaculture ambient. Moreover, under the optimal experiment conditions, this method showed a good linearity between the concentration of CV (c) and fluorescence quenching rate (ΔF/F0) in the concentration range of 4-200 µmol/L with the corresponding correlation coefficient (r) and the detection limit of 0.997 and 710 nmol/L, respectively. With advantages of environmental protectivity, sensitivity, affordability, and user-friendliness, the facilely fabricated CDs could be successfully applied in detecting CV in aquaculture samples, providing a technical foundation for monitoring the pollution of CV and ensuring the quality and safety of aquatic products.

Ratiometric Flapping Force Probe That Works in Polymer Gels.

Polymer gels have recently attracted attention for their application in flexible devices, where mechanically robust gels are required. While there are many strategies to produce tough gels by suppressing nanoscale stress concentration on specific polymer chains, it is still challenging to directly verify the toughening mechanism at the molecular level. To solve this problem, the use of the flapping molecular force probe (FLAP) is promising because it can evaluate the nanoscale forces transmitted in the polymer chain network by ratiometric analysis of a stress-dependent dual fluorescence. A flexible conformational change of FLAP enables real-time and reversible responses to the nanoscale forces at the low force threshold, which is suitable for quantifying the percentage of the stressed polymer chains before structural damage. However, the previously reported FLAP only showed a negligible response in solvated environments because undesirable spontaneous planarization occurs in the excited state, even without mechanical force. Here, we have developed a new ratiometric force probe that functions in common organogels. Replacement of the anthraceneimide units in the flapping wings with pyreneimide units largely suppresses the excited-state planarization, leading to the force probe function under wet conditions. The FLAP-doped polyurethane organogel reversibly shows a dual-fluorescence response under sub-MPa compression. Moreover, the structurally modified FLAP is also advantageous in the wide dynamic range of its fluorescence response in solvent-free elastomers, enabling clearer ratiometric fluorescence imaging of the molecular-level stress concentration during crack growth in a stretched polyurethane film.

In situ label-free and sensitive detection assay for cell apoptosis via polyadenosine-coralyne fluorescence enhancement strategy.

Cell apoptosis detection is vital for biological analysis and clinical application; some detection assays are already commercially available. However, it is still far from perfect and needs further improvement for less cost, time-consuming and operation demanding. TUNEL, a high market share cell apoptosis assay, depends on adulteration fluorescent labelling dUTP by terminal deoxynucleotidyl transferase(TdT) which randomly adds deoxyribonucleoside triphosphates (dNTPs) at the 3'-OH terminal of ssDNA with a template-free manner. Based on our previous work, we adopted a label-free strategy to reduce the cost and operation maintenance of TUNEL and developed a facile, rapid, convenient and in-situ assay for cell apoptosis.

High activity, high selectivity and high biocompatibility BODIPY-pyrimidine derivatives for fluorescence target recognition and evaluation of inhibitory activity.

BODIPY-Pyrimidine (BP) is a highly selective, highly active, and highly biocompatible fluorescent drug, which is characterized by its own activity combined with a fluorophore. The combination of pyrimidines with good biological activity and fluorophores to obtain new compounds with both anti-tumor activity and fluorescent targeting probe functions is the focus of this research. In terms of biological activity, in vitro cytotoxicity of the compounds on four human cancer cells (HepG2, HeLa, A-459, and HCT-116) and the human normal cell line L-02 was studied. BP-4 has good antiproliferative activity, and its IC50 values are 19.12 ± 2.29, 13.47 ± 3.80, 18.59 ± 7.42, 14.57 ± 2.44 and 92.48 ± 6.03 µM, respectively. Good biocompatibility with tumor cells can be observed in cell imaging. The anti-tumor mechanism of the compound was further studied by flow cytometry. After BP-2, BP-3 and BP-4 treated HeLa cells, the percentage of apoptotic cells was 19.07%, 22.09% and 27.3%, respectively. The cell cycle study found that, compared with the positive control 5-FU (48.05%), the compounds BP-2, BP-3 and BP-4 all increased the proportion of HeLa cells in the G1 phase, reaching 57.65%, 55.46% and 53.58%, respectively. In vivo bioimaging results show that all three compounds can be targeted and accurately expressed in tumor tissues. In addition, molecular docking analyzes the possible interaction between the compound and the active site of thymidylate synthase.

Fluorescent polydopamine based molecularly imprinted sensor for ultrafast and selective detection of p-nitrophenol in drinking water.

A highly effective fluorescent molecularly imprinted sensor (F-PDA-MIS) based on fluorescent polydopamine (F-PDA) was successfully synthesized for selective and ultrafast detection of p-nitrophenol (P-NP) in drinking water. F-PDA with abundant surface functional groups has been artfully modified to firstly serve as both fluorescent monomer and functional monomer in the synthesis of a uniform luminous F-PDA-MIS, which can greatly improve the detection efficiency. As expected, F-PDA-MIS had an obvious emission wavelength of 535 nm with the optimal excitation wavelength at 400 nm. Specially, F-PDA-MIS could detect P-NP in the range 100 to 1100 nM with much lower detection limit of 24.2 nM within 120 s compared with other conventional imprinted fluorescent sensors based on pure quantum dots (QDs) or dyes. This excellent test phenomenon is mainly ascribed to the rapid electron transfer between F-PDA and P-NP. Satisfactory recovery of 98.0-104% for mineral water and 98.6-106% for boiling water were obtained with relative standard deviations (RSDs) of 2.7-3.4% and 2.6-3.5% respectively. The detection reliability of F-PDA-MIS was verified by the comparison with high-performance liquid chromatography (HPLC-UV). Consequently, F-PDA as a fluorescence functional monomer has been shown to be a possible strategy to effectively improve the detection limit and shorten response time of the target determination in water..

Dual-emission copper nanoclusters-based ratiometric fluorescent probe for intracellular detection of hydroxyl and superoxide anion species.

A fluorescent nanoprobe based on copper nanoclusters (CuNCs) has been developed for ratiometric detection of hydroxyl radicals (•OH) and superoxide anion radicals (O2•-). Two differently luminescent CuNCs, namely cyan-emissive poly(methacrylic acid)-protected copper nanoclusters (PCuNCs) and orange-emissive bovine serum albumin-protected CuNCs (BCuNCs), were conjugated to obtain a hybrid, dual-emission nanoprobe (PCuNCs-BCuNCs) with the corresponding peaks at 445 nm and 652 nm at an excitation wavelength of 360 nm. In particular, the fluorescence peak at 445 nm gradually enhanced with the incremental addition of •OH and O2•-. However, the fluorescence emission at 652 nm was greatly quenched in the presence of •OH, while in case of O2•-, the fluorescence intensity remained constant. The differential response of the PCuNCs-BCuNCs towards •OH and O2•- formed the basis of ratiometric detection. Under optimal conditions, the PCuNCs-BCuNCs exhibited good sensitivity and linearity towards •OH and O2•- with limits of detection of 0.15 µM and 1.8 µM, respectively. Moreover, the nanoprobe exhibited high selectivity for •OH and O2•- over other potential ROS interferences. Besides, PCuNCs-BCuNCs were eventually applied for qualitative and quantitative ratiometric assessment of intracellular •OH and O2•- in L-132 cells. Therefore, this strategy unveils a new potential for copper nanocluster-based sensing of ROS.

Imprinted ß-ketoenamine-linked covalent organic frameworks as dispersive sorbents for the fluorometric determination of timolol.

Timolol accompanied the formation of fluorescent ß-ketoenamine-linked covalent organic frameworks (COFs) via the Sc(Tof)3-catalyzed condensation of derivated carbaldehyde and hydrazide in a 1,4-dioxane/mesitylene porogen to construct timolol-imprinted COFs (TICOFs). With high imprinting factors, the synthesis-optimized TICOFs were characterized by fluorescence, UV-Vis spectrometry, X-ray diffraction, N2 adsorption/desorption analyses, scanning electron microscopy, and FTIR spectrometry. The TICOF fluorescence measured at 390 nm/510 nm is dynamically quenched by timolol and was thus utilized to quantify timolol in a linear range of 25-500 nM with a LOD of 8 nM. The TICOF recovered 99.4% of 0.5% timolol maleate in a commercial eye drop (RSD = 1.1%, n = 5). In addition, TICOF was used as a dispersive sorbent to recover 95% of 2.0 nM timolol from 20 mg of TICOF in 25 mL phosphate buffer. Dilution factors of 25 and 75 were the maximum tolerated proportions of the urine and serum matrix spiked with 2.0 nM timolol to reach recoveries of 92.4% and 90.3%, respectively.

Near-Infrared-Emitting Boron-Difluoride-Curcuminoid-Based Polymers Exhibiting Thermally Activated Delayed Fluorescence as Biological Imaging Probes.

Near-infrared-emitting polymers were prepared using four boron-difluoride-curcuminoid-based monomers using ring-opening metathesis polymerization (ROMP). Well-defined polymers with molecular weights of ≈20 kDa and dispersities <1.07 were produced and exhibited near-infrared (NIR) emission in solution and in the solid state with photoluminescence quantum yields (ΦPL ) as high as 0.72 and 0.18, respectively. Time-resolved emission spectroscopy revealed thermally activated delayed fluorescence (TADF) in polymers containing highly planar dopants, whereas room-temperature phosphorescence dominated with twisted species. Density functional theory demonstrated that rotation about the donor-acceptor linker can give rise to TADF, even where none would be expected based on calculations using ground-state geometries. Incorporation of TADF-active materials into water-soluble polymer dots (Pdots) gave NIR-emissive nanoparticles, and conjugation of these Pdots with antibodies enabled immunofluorescent labeling of SK-BR3 human breast-cancer cells.

Biodegradable Polymersomes with Structure Inherent Fluorescence and Targeting Capacity for Enhanced Photo-Dynamic Therapy.

Biodegradable nanostructures displaying aggregation-induced emission (AIE) are desirable from a biomedical point of view, due to the advantageous features of loading capacity, emission brightness, and fluorescence stability. Herein, biodegradable polymers comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG-P(CLgTMC)), with tetraphenylethylene pyridinium-TMC (PAIE) side chains have been developed, which self-assembled into well-defined polymersomes. The resultant AIEgenic polymersomes are intrinsically fluorescent delivery vehicles. The presence of the pyridinium moiety endows the polymersomes with mitochondrial targeting ability, which improves the efficiency of co-encapsulated photosensitizers and improves therapeutic index against cancer cells both in vitro and in vivo. This contribution showcases the ability to engineer AIEgenic polymersomes with structure inherent fluorescence and targeting capacity for enhanced photodynamic therapy.

Single-Chain Nanoparticle Delivers a Partner Enzyme for Concurrent and Tandem Catalysis in Cells.

Combining synthetic chemistry and biocatalysis is a promising but underexplored approach to intracellular catalysis. We report a strategy to codeliver a single-chain nanoparticle (SCNP) catalyst and an exogenous enzyme into cells for performing bioorthogonal reactions. The nanoparticle and enzyme reside in endosomes, creating engineered artificial organelles that manufacture organic compounds intracellularly. This system operates in both concurrent and tandem reaction modes to generate fluorophores or bioactive agents. The combination of SCNP and enzymatic catalysts provides a versatile tool for intracellular organic synthesis with applications in chemical biology.

Bispyrene-Based Self-Assembled Nanomaterials: In Vivo Self-Assembly, Transformation, and Biomedical Effects.

Self-assembled nanomaterials show potential high efficiency as theranostic agents for high-performance imaging and therapy. However, superstructures and properties of preassembled nanomaterials are somewhat compromised under complicated physiological conditions. Given the advantages of the dynamic nature and adaptive behavior of self-assembly systems, we propose an "in vivo self-assembly" strategy for in situ construction of nanomaterials in living objects. For the proof-of-concept study of in vivo self-assembly, we developed a bispyrene (BP) molecule as a multifunctional building block. BP molecules show nonfluorescence in the monomeric state. Quantum-chemical calculations indicate that BP forms twisted intramolecular charge transfer states, which are separated into two orthogonal units, preventing the fluorescence emission. Interestingly, the typical excimeric emission of BP is observed with the formation of J-type aggregates, as confirmed by single-crystal X-ray diffraction. Packing of the BP molecules generates parallel pyrene units that interact with adjacent ones in a slipped face-to-face fashion through intermolecular π-π interactions. BP and/or its amphiphilic derivatives are capable of self-aggregating into nanoparticles (NPs) in aqueous solution because of the hydrophobic and π-π interactions of BP. Upon specific biological stimuli, BP NPs can be transformed into variable self-assembled superstructures. Importantly, the self-assembled BP NPs exhibit turn-on fluorescence signals that can be used to monitor the self-assembly/disassembly process in vitro and in vivo. On the basis of the photophysical properties of BP and its aggregates, we synthesized a series of designed BP derivatives as building blocks for in situ construction of functional nanomaterials for bioimaging and/or therapeutics. We observed several new biomedical effects, e.g., (i) the assembly/aggregation-induced retention (AIR) effect, which shows improved accumulation and retention of bioactive nanomaterials in the regions of interests; (ii) the transformation-induced surface adhesion (TISA) effect, which means the BP NPs transform into nanofibers (NFs) on cell surfaces upon binding with specific receptors, which leads to less uptake of BP NPs by cells via traditional endocytosis pathway; and (iii) transformation of the BP NPs into NFs in the tumor microenvironment, showing high accumulation and long-term retention, revealing the transformation-enhanced accumulation and retention (TEAR) effect. In this Account, we summarize the fluorescence property and emission mechanism of BP building blocks upon aggregation in the biological environment. Moreover, BP-derived compounds used for in vivo self-assembly and transformation are introduced involving modulation strategies. Subsequently, unexpected biomedical effects and applications for theranostics of BP based nanomaterials are discussed. We finally conclude with an outlook toward future developments of BP-based self-assembled nanomaterials.

Fluorogenic glycopolymers available for determining the affinity of lectins by intermolecular FRET.

A convenient assembly of fluorogenic glycopolymers having various polymer compositions was accomplished from the corresponding glycomonomer and dansyl monomer by means of radical polymerization, and the water-soluble glycopolymers gave typical fluorescence spectroscopic profiles due to the dansyl moieties on the glycopolymer in aqueous media. Biological evaluation of the polymer against wheat germ agglutinin (WGA) was accomplished on the basis of fluorescence changes due to tryptophan residues on WGA, and the affinities between the glycopolymers and WGA were estimated to be 4.7 × 105 to 9.3 × 105 M-1. In order to apply the fluorogenic glycopolymers for further biological measurements, efficient resonance energy transfer from tryptophan moieties on WGA to dansyl moieties on the fluorogenic glycopolymers was examined. FRET profiles of both fluorophores were similar compared to the binding profiles on the basis of fluorescence changes of tryptophan residues. This approach is applicable for the determination of an affinity constant between a carbohydrate and a lectin in which no fluorophore exists near the binding site.

Design and synthesis of a novel BODIPY-labeled PSMA inhibitor.

Prostate-specific membrane antigen (PSMA) is a zinc-bound metalloprotease which is highly expressed in metastatic prostate cancer. It has been considered an excellent target protein for prostate cancer imaging and targeted therapy because it is a membrane protein and its active site is located in the extracellular region. We successfully synthesized and evaluated a novel PSMA ligand conjugated with BODIPY650/665. Compound 1 showed strong PSMA-inhibitory activity and selective uptake into PSMA-expressing tumors. Compound 1 has the potential to be utilized as a near infrared (NIR) optical imaging probe targeting PSMA-expressing cancers.

Selective Recognition of Herbicides in Water Using a Fluorescent Molecularly Imprinted Polymer Sensor.

Fluorescent molecularly imprinted polymer (FMIP) optosensor was utilized for the selective identification of 2,4-dichlorophenoxacetic acid (2,4-D) due to worldwide pollution caused by using herbicides in agricultural industry. In this regards, two derivatives of polymerizable 1,8-naphthalimide namely, 1,8-naphthalimide containing thiourea (NI) and diethyl amine tagged 1,8-naphthalimide (NII) were used as the receptors and 2,4-D was applied as a template. Also, precipitation polymerization was applied to prepare the fluorescent molecularly imprinted polymer (FMIP). The morphological, structural and thermal analysis was carried out using SEM, TEM, EDS, BET, FTIR, DSC and TGA for characterizing the fluorescent optosensor. The adsorption efficiency of FMIP and FNIP was studied using Langmuir, Freundlich, BET and Redlich Peterson isotherms. The results represented that the adsorption of 2,4-D on FMIP and FNIP agreed the Freundlich adsorption isotherm with correlation coefficient of 0.9935 and 0.9801, respectively. The prepared sensor was able for the selective determination of 2,4-D salt in the linear range of 5 × 10-7-1 × 10-3 M with a limit of detection of 16.8 nM. The present study revealed that the FMIP prepared by 1,8-naphthalimide derivative (NI) could potentially recognize the trace concentration of 2,4-D. Graphical Abstract Graphical abstract of flourescene switching mechanism in a fluorescent molecularly imprinted polymer sensor.

A Fluorescent Zn(II) Coordination Polymer: Sensitive Detection of Cr2O72- in Water and Prevention Activity On the Deep Vein Thrombosis in Orthopedic Nursing.

A novel coordination polymer (CP) based on Zn(II) of [Zn(tptc)0.5(bpy)(H2O)]n (1) was synthesized through utilizing the 2,2'-bipyridine (bpy) chelating N donors and p-terphenyl-2,2'',5'',5'''-tetracarboxylate acid (H4tptc) as the co-ligands. The measurements of the fluorescence were implemented for the complex 1 in solution and solid state, and the result reveals that 1 has a strong fluorescence and it is a sensory material with great development space to determine the trace Cr2O72- (with the detection limit of 36 ppb) in the water solutions via applying the fluorescence quenching effect. As the common disease in the orthopedic nursing, the deep vein thrombosis was the objective in this research. The weigh and length of the thrombus in the animals were measured and analyzed. In addition to this, the inflammatory response in the deep vein thrombosis animal was evaluated by RT-PCR. Molecular docking results indicate that only the carboxyl group could provide polar oxygen atoms for the formed hydrogen bonds to the protein.

A Fluorescent Zn(II)-Coordination Polymer: Selective Detection of Nitrofurantoin and Prevention of Peri-Implantitis after Ultrafine-Grained Titanium Implant by Reducing Inflammatory Cytokines Release.

In the current research, a novel coordination polymer (CP) containing Zn(II) ions as nodes with the chemical formula of [Zn(IPT)2]n (1) has been produced via reaction of Zn(NO3)2·6H2O with 5-(3-(1H-imidazol-1-yl)phenyl)-1H-tetrazolate (HIPT), a heterotopic imidazole-tetrazole-bifunctional ligand. The as-prepared complex 1 has been charactered via single crystal X-ray diffraction, elemental analysis, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA) and fourier transform infrared spectroscopy (FT-IR). Because of its outstanding luminescent performances and stability, the synthesized complex 1 is a kind of excellent material of luminescent sensor of nitrofurantoin (NFT) in the water. The value of Ksv for the complex 1 to NFT is about 1.4 × 104 M-1. For the treatment of the peri-implantitis with complex 1, the ELISA test was carried out to determine the levels of the inflammatory cytokines released into the gingival crevicular fluid. The results showed that the levels of the inflammatory cytokines could be significantly reduced by complex 1 treatment. In addition to this, the real time RT-PCR was also conducted, and the data suggested the signaling pathway of TLR-4-NF-κB activation was inhibited by complex 1.

Mechanochromic Polymers Based on Microencapsulated Solvatochromic Dyes.

The development of polymers with built-in sensors that provide readily perceptible optical warning signs of mechanical events has received considerable interest. A simple and versatile concept to bestow polymers with mechanochromic behavior is the incorporation of dye-filled microcapsules. Such capsules release their cargo when their shell is damaged, and the dye is subsequently activated through a chemical or physical change that causes a chromogenic response. Here, we report the preparation of fluorescent poly(urea-formaldehyde) microcapsules containing solutions of a solvatochromic cyanostilbene dye and their integration in different polymers. When objects made from such composites are damaged, the dye solution is released from the containers, diffuses into the matrix, and the solvent evaporates. As a result, the polarity around the dye molecules changes, and this leads to a change of the fluorescence color. Alternatively, the dye is blended into the polymer matrix, microcapsules are loaded with a solvent, and the release of the latter triggers the color change. Both mechanisms afford ratiometric signals because the capsules that remain intact or dye molecules that are not exposed to the solvent can be used as a built-in reference; therefore, a quantitative assessment of the damage inflicted on the material is a priori possible.

Isocyanoacetate-Aldehyde Polymerization: A Facile Tool toward Functional Oxazoline-Containing Polymers.

As an important nitrogen source, isocyanides have been involved in numerous organic reactions. As a result, many complicated compounds have been successfully synthesized through isocyanide chemistry. However, compared with its popular research in organic reactions, the application of isocyanides in polymerization is less investigated. In this work, a new polymerization based on isocyanide monomers is established. By simply mixing diisocyanoacetates and dialdehydes in the presence of a catalytic system of CuCl/PPh3 /organobase in dichloromethane at room temperature readily produces soluble and thermally stable oxazoline-containing polymers with moderate weight-averaged molecular weights (Mw up to 11 200) in excellent yields (up to 97%) after 6 h. Furthermore, introducing the tetraphenylethene moiety into the main chains endows the resultant polymers with aggregation-induced emission, which can function as fluorescent probes for Fe3+ ion detection with high sensitivity and selectivity. This work not only enriches the family of isocyanide-based polymerizations but also provides an efficient tool for the preparation of functional heterocycle-containing polymers.

TAMRA-polypyrrole for A/T sequence visualization on DNA molecules.

Fluorophore-linked, sequence-specific DNA binding reagents can visualize sequence information on a large DNA molecule. In this paper, we synthesized newly designed TAMRA-linked polypyrrole to visualize adenine and thymine base pairs. A fluorescent image of the stained DNA molecule generates an intensity profile based on A/T frequency, revealing a characteristic sequence composition pattern. Computer-aided comparison of this intensity pattern with the genome sequence allowed us to determine the DNA sequence on a visualized DNA molecule from possible intensity profile pattern candidates for a given genome. Moreover, TAMRA-polypyrrole offers robust advantages for single DNA molecule detection: no fluorophore-mediated photocleavage and no structural deformation, since it exhibits a sequence-specific pattern alone without the use of intercalating dyes such as YOYO-1. Accordingly, we were able to identify genomic DNA fragments from Escherichia coli cells by aligning them to the genomic A/T frequency map based on TAMRA-polypyrrole-generated intensity profiles. Furthermore, we showed band and interband patterns of polytene chromosomal DNA stained with TAMRA-polypyrrole because it prefers to bind AT base pairs.