Supramolecular Host-Guest Strategy for the Accelerating Detection of Nitroreductase.

Identifying nitroreductase (NTR) with fluorescent techniques has become a research hotspot, due to its good sensitivity and selectivity toward the early-stage cancer diagnosis and monitoring. Herein, a host-guest reporter (NAQA⊂Zn-MPPB) is successfully achieved by encapsulating the NTR probe NAQA into a new NADH-functioned metal-organic cage Zn-MPPB, which makes the reporter for ultrafast detection of NTR within dozens of seconds in solution. The host-guest strategy fuses the Zn-MPPB and NAQA to form a pseudomolecule material, which changes the reaction process of NTR and NAQA from a double substrates mechanism to a single substrate one, and accelerates the reduction efficiency of NAQA. This advantage make the new host-guest reporter exhibit a linear relationship between emission changes and NTR concentration, and it shows better sensitively toward NTR than that of NAQA. Additionally, the positively charged water-soluble metal-organic cage can encapsulate NAQA in the cavity, promote it to dissolve in an aqueous environment, and facilitate their accumulation into tumor cells. As expected, such host-guest reporter displays a fast and high efficiently imaging capability toward NTR in tumor cells and tumor-bearing mice, and flow cytometry assay is conducted to corroborate the capability as well, implying the considerably potential of host-guest strategy for early tumor diagnosis and treatment.

A Diode-Like Dye-Cu Anisotropic Junction in a Coordination Polymer as a Logic State Ratchet for Intratumor Redox Photomodulation.

Redox logic materials offer new avenues to modulate intracellular pathologic redox environment area-specifically, but the unambiguity of redox logic states and their unidirectional and repetitive switchability are challenging to realize. By merging a bistable diisophthalic phenazine dye ligand with CuII salt, a multistable coordination polymer (CP) was constructed, of which the dye-Cu anisotropic junction achieved the diode-like unidirectional electron transfer and logic state ratchet for the first time. Radical cationic CP maintained OFF status with low toxicity in healthy tissues, but was reduced to the neutral SERVO state by the overexpressed glutathione (GSH) in hypoxic tumors. After photoirradiation, the stabilized charge-separated ON status promoted photo-Fenton reaction for reactive oxygen species (ROS) signal transduction, and simultaneously recovered the initial state for catalytic signal amplification of ROS, furnishing intratumor redox photomodulation for therapy.

Synthesis of Homoallylic Amines by Radical Allylation of Imines with Butadiene under Photoredox Catalysis.

Ionic (2 e- ) nucleophilic addition of allylmetal regents to imines dominates the synthesis of homo-allyl amine; however, single electron (1 e- ) mediated imine allylation with feedstocks butadiene as an alternative allyl source remains unexplored. In this work, we report a conceptually different radical-radical cross-coupling strategy for the synthesis of a homoallyl amine between an α-amino alkyl radical and a transient allylic radical. This metal-free method provided a novel approach for the synthesis of homoallylic amines (>80 examples) from readily available materials with excellent regioselectivity and exceptional broad functional group compatibility.

Iron-Catalyzed Photoredox Functionalization of Methane and Heavier Gaseous Alkanes: Scope, Kinetics, and Computational Studies.

Herein, we report the development of the photocatalytic C-H functionalization of methane, ethane, and heavier gaseous alkanes with good yields and selectivity, broad scope (57 examples), mild conditions, and low cost. Kinetics and density functional theory calculations were investigated for the key photoinduced ligand-to-metal charge transfer and hydrogen atom transfer processes to reveal the detailed mechanism of iron photocatalysis. This work may bring novel ideas for feedstock upgrading and catalyst design.

Synthesis of a Lanthanide Metal-Organic Framework and Its Fluorescent Detection for Phosphate Group-Based Molecules Such as Adenosine Triphosphate.

Adenosine triphosphate (ATP) is an important kind of metabolized biological molecule that is formed in organisms, especially in mitochondria, is used universally as energy, and is one of the most significant multifunctional biological molecules. Metal-organic frameworks (MOFs) have been widely used in many applications such as gas storage and separation, drug delivery, heterogeneous catalysis, chemical sensors, etc. Remarkably, lanthanide MOFs (Ln-MOFs), which display large pores, multiple dimensions, and unique lanthanide luminescence properties, are widely used as chemical sensors. A novel three-dimensional probe, Eu2(sbdc)3(H2O)3 (Eu-sbdc), was successfully self-assembled with Eu(NO3)3·6H2O and 5,5-dioxo-5H-dibenzo[b,d]thiophene-3,7-dicarboxylic acid (H2sbdc). The Ln-MOF Eu-sbdc can quickly and effectively optically detect ATP via a luminescent quenching mechanism. The Ksv value of Eu-sbdc is 1.02 × 104 M-1, and the lower detection limit of Eu-sbdc for ATP is 20 µM, which is more sensitive to ATP. Its mechanism of monitoring ATP might be a dynamic or static quenching process. Eu-sbdc could effectively and quickly recognize ATP with high sensitivity.

A Novel Fluorescent Probe for Hydrogen Peroxide and Its Application in Bio-Imaging.

Hydrogen peroxide (H2O2) plays an important role in the human body and monitoring its level is meaningful due to the relationship between its level and diseases. A fluorescent sensor (CMB) based on coumarin was designed and its ability for detecting hydrogen peroxide by fluorescence signals was also studied. The CMB showed an approximate 25-fold fluorescence enhancement after adding H2O2 due to the interaction between the CMB and H2O2 and had the potential for detecting physiological H2O2. It also showed good biocompatibility and permeability, allowing it to penetrate cell membranes and zebrafish tissues, thus it can perform fluorescence imaging of H2O2 in living cells and zebrafish. This probe is a promising tool for monitoring the level of H2O2 in related physiological and pathological research.

Cu Nanocluster-Loaded TiO2 Nanosheets for Highly Efficient Generation of CO-Free Hydrogen by Selective Photocatalytic Dehydrogenation of Methanol to Formaldehyde.

Safe storage and transportation of H2 is a fundamental requirement for its wide applications in the future. Controllable release of high-purity H2 from a stable storage medium such as CH3OH before use offers an efficient way of achieving this purpose. In our case, Cu nanoclusters uniformly dispersed onto (001) surfaces of TiO2 nanosheets (TiO2/Cu) are selectively prepared by thermal treatment of HKUST-1 loaded TiO2 nanosheets. One of the TiO2/Cu composites, TiO2/Cu_50, exhibits remarkably high activity toward the selective dehydrogenation of CH3OH to HCHO with a H2 evolution rate of 17.8 mmol h-1 per gram of catalyst within a 16-h photocatalytic reaction (quantum efficiency at 365 nm: 16.4%). Theoretical calculations reveal that interactions of Cu nanoclusters with TiO2 could affect their electronic structures, leading to higher adsorption energy of CH3OH at Ti sites and a lower barrier for the dehydrogenation of CH3OH by the synergistic effect of Cu nanoclusters and TiO2, and lower Gibbs free energy for desorption HCHO and H2 as well.

Lighting up metallohelices: from DNA binders to chemotherapy and photodynamic therapy.

The design of novel agents that specifically target DNA and interrupt its normal biological processes is an attractive goal in drug design. Among the promising metallodrugs, metal-directed self-assembled metallohelices with defined three-dimensional stereochemical structures display unique structure-inherent and unprecedented noncovalent targeting abilities towards DNA, resulting in excellent anticancer or antibiotic activities. A newly burgeoning hotspot is focusing on lighting them up by embedding luminescent metal ions as the vertices. The photoactive metallohelices that combine strong interactions toward DNA targets and efficient 1O2 quantum yield may provide new motivation in diagnostic and photodynamic therapy (PDT) areas. This perspective focuses on research progress on metallohelices as DNA binders and chemotherapeutic agents, and highlights recent advances in fabricating luminescent examples for PDT. The relative assembly strategies are also discussed and compared. Finally, perspectives on the future development of the lit-up metallohelices are presented.

Tailoring nanoparticles based on boron dipyrromethene for cancer imaging and therapy.

Boron dipyrromethene (BODIPY), as a traditional fluorescent dye, has drawn increasing attention because of its excellent photophysical properties like adjustable spectra and outstanding photostability. BODIPY dyes could be assembled into nanoparticles for cancer imaging and therapy via rational design. In this review, the bio-applications of BODIPY-containing nanoparticles are introduced in detail, such as cellular imaging, near-infrared fluorescence imaging, computed tomography imaging, photoacoustic imaging, phototherapy, and theranostics. The construction strategies of BODIPY-containing nanoparticles are emphasized so the review has three sections-self-assembly of small molecules, chemical conjugation with hydrophilic compounds, and physical encapsulation. This review not only summarizes various and colorific bio-applications of BODIPY-containing nanoparticles, but also provides reasonable design methods of BODIPY-containing nanoparticles for cancer theranostics. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging.

Mitochondrial-DNA-Targeted IrIII -Containing Metallohelices with Tunable Photodynamic Therapy Efficacy in Cancer Cells.

The development of DNA-targeted photodynamic therapy (PDT) agents for cancer treatment has drawn substantial attention. Herein, the design and synthesis of dinuclear IrIII -containing luminescent metallohelices with tunable PDT efficacy that target mitochondrial DNA in cancer cells are reported. The metallohelices are fabricated using dynamic imine-coupling chemistry between aldehyde end-capped fac-Ir(ppy)3 handles and linear alkanediamine spacers, followed by reduction of the imine linkages. The length and odd-even character of the diamine alkyl linker determined the stereochemistry (helicates vs. mesocates). Compared to the helicates, the mesocates exhibit improved apoptosis-induction upon white-light irradiation. Molecular docking studies indicate that the mesocate with a proper length of diamine spacers shows stronger affinity for the minor groove of DNA. This study highlights the potential of DNA-targeting IrIII -containing metallohelices as PDT agents.

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.

A Cofactor-Substrate-Based Supramolecular Fluorescent Probe for the Ultrafast Detection of Nitroreductase under Hypoxic Conditions.

Identifying the location and expression levels of enzymes under hypoxic conditions in cancer cells is vital in early-stage cancer diagnosis and monitoring. By encapsulating a fluorescent substrate, L-NO2 , within the NADH mimic-containing metal-organic capsule Zn-MPB, we developed a cofactor-substrate-based supramolecular luminescent probe for ultrafast detection of hypoxia-related enzymes in solution in vitro and in vivo. The host-guest structure fuses the coenzyme and substrate into one supramolecular probe to avoid control by NADH, switching the catalytic process of nitroreductase from a double-substrate mechanism to a single-substrate one. This probe promotes enzyme efficiency by altering the substrate catalytic process and enhances the electron transfer efficiency through an intra-molecular pathway with increased activity. The enzyme content and fluorescence intensity showed a linear relationship and equilibrium was obtained in seconds, showing potential for early tumor diagnosis, biomimetic catalysis, and prodrug activation.

Engineering pH-Responsive BODIPY Nanoparticles for Tumor Selective Multimodal Imaging and Phototherapy.

It is a challenge to develop multifunctional theranostic agents in one molecule, which simultaneously possesses tumor imaging ability with a high signal-to-noise ratio and excellent therapeutic activity. In this work, we synthesized and screened a series of BODIPY (BDP) with various absorption and fluorescence. The interplay of the molecular structure, pH-sensitive absorption and emission, and photodynamic and photothermal activities was well studied in detail. Photoinduced electron transfer, intramolecular charge transfer, and heavy atom effect were leveraged to engineer BDP with tumor imaging and therapeutic functions. The BDP nanoparticle formulations possessed multifunctional biological features, including selective treatment of cancer cells, near-infrared fluorescence, photoacoustic and computed tomography imaging, and photodynamic and photothermal therapy, as validated by cellular and animal experiments. These results not only give a new horizon to multifunctional BDP for biological applications but also show a new way to design the organic dye for tumor imaging and phototherapy.

A Novel Ratiometric Fluorescent Probe for Mercury (II) ions and Application in Bio-imaging.

Since the accumulation of mercury (II) ions in the environment and ecosystem causes serious problems to environment and disease, the recognition of Hg2+ ions and its bio-imaging is of high importance. In sight of the advantages of fluorescence probes, a new probe (PMH) was facilely synthesized by incorporating phenylimidazole fluorophore and 3-methyl-2- benzothiazolinone hydrazone hydrochloride monohydrate. The PMH probe exhibited a ratiometric response for Hg2+ ions with fluorescence intensity increasing at 520 nm and decreasing at 445 nm simultaneously. The PMH probe interacted with Hg2+ ions in seconds with high optical stability and showed good selectivity over other metal ions. In addition, the probe has excellent biocompatibility and imaging performance in cells and zebrafish.

Conformationally Induced Off-On Cell Membrane Chemosensor Targeting Receptor Protein-Tyrosine Kinases for in Vivo and in Vitro Fluorescence Imaging of Cancers.

Molecules capable of monitoring receptor protein-tyrosine kinase expression could potentially serve as useful tools for cancer diagnosis due to the overexpression of tyrosine kinases during tumor growth and metastasis. In this work, a conformationally induced "off-on" tyrosine kinase cell membrane fluorescent sensor (SP1) was designed and evaluated for the detection and imaging of receptor protein-tyrosine kinases in vivo and in vitro. SP1 consists of sunitinib and pyrene linked via hexamethylenediamine and displays quenched fluorescence as a dimer. The fluorescence of SP1 is restored in the presence of receptor protein-tyrosine kinases upon strong interaction with SP1 at the target terminal. The unique signal response mechanism enables SP1 use for fluorescence microscopy imaging of receptor protein-tyrosine kinases in the cell membranes of living cells, allowing for the rapid differentiation of cancer cells from normal cells. SP1 can be used to visualize the chick embryo chorioallantoic membrane and mouse model tumors, suggesting its possible application for early cancer diagnosis.

Two-dimensional nickel hydroxide/sulfides nanosheet as an efficient cocatalyst for photocatalytic H2 evolution over CdS nanospheres.

The intriguing features of two-dimensional (2D) materials such as better charge carrier separation and abundant surface reaction sites endow them with potential applications as cocatalysts in photocatalysis. In this paper, a ternary 2D nickel hydroxide/sulfides nanosheet composed of Ni(OH)2, Ni3S2 and NixS6 was loaded on CdS nanospheres by a simple chemical deposition route. The composition of nickel hydroxide/sulfides was determined clearly through an overall analysis using X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy. Mott-Schottky, electrochemical impedance, steady-state and time-resolved photoluminescence spectroscopy were used to investigate the charge transfer process in CdS and Ni(OH)2/Ni3S2/NixS6-CdS. The results confirm that a synergistic effect of Ni(OH)2/Ni3S2/NixS6 on CdS has occurred under light irradiation, where the Ni(OH)2 and nickel sulfides act as hole storage and surface reaction sites, respectively, to promote the charge transfer on CdS. The improved charge transfer and separation efficiency as well as the increased surface reaction sites in Ni(OH)2/Ni3S2/NixS6-CdS finally result in a dramatically improved photocatalytic performance. The photocatalytic H2 evolution rate of Ni(OH)2/Ni3S2/NixS6-CdS is ca. 46 times higher than that of CdS, and the photocatalytic stability of CdS is also improved substantially under visible light irradiation.

DHPA-Containing Cobalt-Based Redox Metal-Organic Cyclohelicates as Enzymatic Molecular Flasks for Light-Driven H2 Production.

The supramolecular assembly of predesigned organic and inorganic building blocks is an excellent tool for constructing well-defined nanosized molecular cavities that catalyse specific chemical transformations. By incorporating a reduced nicotinamide adenine dinucleotide (NADH) mimic within the ligand backbone, a redox-active cobalt-based macrocycle was developed as a redox vehicle for the construction of an artificial photosynthesis (AP) system. The cyclohelicate can encapsulate fluorescein within its cavity for light-driven H2 evolution, with the turnover number (TON) and turnover frequency (TOF) reaching 400 and 100 moles H2 per mole redox catalyst per hour, respectively. Control experiments demonstrated that the reactions were potentially occurred within the cavity of the cyclohelicates which were inhibited in the presence of adenosine triphosphate (ATP), and the redox-active NADH mimic dihydropyridine amido moieties within the ligands played an important role in photocatalytic proton reduction process.

New rht-Type Metal-Organic Frameworks Decorated with Acylamide Groups for Efficient Carbon Dioxide Capture and Chemical Fixation from Raw Power Plant Flue Gas.

The combination of carbon dioxide capture and chemical fixation in a one-pot process is attractive for both chemists and governments. The cycloaddition of carbon dioxide with epoxides to produce cyclic carbonates is an atomic economical reaction without any side products. By incorporating acylamide to enhance the binding affinity toward CO2, new rht-type metal-organic frameworks (MOFs) with (3, 28) and (3, 24) connected units were constructed. Zn-NTTA with two types of dinuclear paddlewheel building blocks-{Zn2(OOC-)4} and {Zn2(OOC-)3}. The high uptake of CO2 (115.6 cm3·g-1) and selectivity over N2 (30:1) at 273 K indicated that these MOFs are excellent candidates for postcombustion CO2 isolation and capture. The MOFs feature high catalytic activity, rapid dynamics of transformation and excellent stability with turnover number (TON) values up to 110 000 per paddlewheel unit after 5 × 6 rounds of recyclability, demonstrating that they are promising heterogeneous catalysts for CO2 cyclo-addition to value-added cyclic carbonates. The cycloaddition of epoxides with wet gases demonstrated that the catalyst activity was not affected by moisture, and the indices of the PXRD patterns of the bulk samples filtered from the catalytic reaction revealed that the crystallinities were maintained. The combination of the selective capture and catalytic transformation in one-pot enables the use of a negative-cost feedstock-raw power plant flue gas without any separation and purification-revealing the broad prospects of such MOFs for practical CO2 fixation in industry.

A highly selective and sensitive ON-OFF-ON fluorescence chemosensor for cysteine detection in endoplasmic reticulum.

A new complex between coumarin-based ligand (CL) and copper ion has been prepared and applied to be an ON-OFF-ON reversible fluorescence chemosensor for the detection of Cys with high sensitivity and specificity. In HEPES buffer, CL displayed high affinity towards Cu(2+) ion over other physiological and environmental metal ions, accompanied with a 98.4% of fluorescence quenching. In the presence of Cys, the detachment of Cu(2+) ion of CL-Cu(2+) ensemble led to the liberation of the fluorophore, CL, and thus fluorescence was recovered. The results of absorption and emission spectroscopy analyses confirmed that the fluorescence turn ON response of CL-Cu(2+) ensemble was selective towards Cys only with high sensitivity (detection of limit, 7.2×10(-7) M). Confocal microscopy studies indicated that the lipophilic CL targets the endoplasmic reticulum (ER) of live cells, where it could be functioned as a fluorescent chemosensor for visualization of Cys in this organelle. Quantitative fluorescence detection of Cys in ER was successfully realized by flow cytometry analysis. The developed chemosensor was further applied to detect Cys in real urine samples with great recoveries ranges from 95.41% to 107.40%.

Amplifying the red-emission of upconverting nanoparticles for biocompatible clinically used prodrug-induced photodynamic therapy.

A class of biocompatible upconverting nanoparticles (UCNPs) with largely amplified red-emissions was developed. The optimal UCNP shows a high absolute upconversion quantum yield of 3.2% in red-emission, which is 15-fold stronger than the known optimal ß-phase core/shell UCNPs. When conjugated to aminolevulinic acid, a clinically used photodynamic therapy (PDT) prodrug, significant PDT effect in tumor was demonstrated in a deep-tissue (>1.2 cm) setting in vivo at a biocompatible laser power density. Furthermore, we show that our UCNP-PDT system with NIR irradiation outperforms clinically used red light irradiation in a deep tumor setting in vivo. This study marks a major step forward in photodynamic therapy utilizing UCNPs to effectively access deep-set tumors. It also provides an opportunity for the wide application of upconverting red radiation in photonics and biophotonics.