A novel strategy for ratiometric determination of o-phenylenediamine via in-situ fluorogenic reaction and generation of metal nanoparticles.

Herein, a novel ratiometric strategy for ultra-sensitive detection of o-phenylenediamine (OPD) was proposed based on combinatorial reactions of in-situ fluorogenic reaction and in-situ formation of red fluorescent dithiothreitol-copper nanoparticles (DTT-CuNPs). Here, Cu2+ is used both as an oxidant and as a precursor. Dehydroascorbic acid (DHAA) is formed via redox reaction of AA and Cu2+. Then, DHAA reacts with OPD to yield blue fluorescent quinoxaline (OXD) with emission peak at 434 nm through in-situ fluorogenic reaction. Red emitting DTT-CuNPs with emission peak at 666 nm is instantly generated due to the coordination reaction between DTT and the residual Cu2+ which is not consumed by AA. The fluorescence intensity (FI) of OXD at 434 nm is closely relied on the concentration of OPD, which can be used as a response signal for OPD detection. Meanwhile, FI of DTT-CuNPs at 666 nm has no significant change, which can be used as a reference signal for OPD detection. Thus, the ratio (F434/F666) of the Cu2+/AA/DTT sensing system is successfully employed to quantify OPD, exhibiting a wide linear range from 0.2 µM to 60 µM, with LOD of 0.09 µM.

A review: Small organic molecule dual/multi-organelle-targeted fluorescent probes.

In recent years, the dual/multi-organelle-targeted fluorescent probe based on small organic molecules has good biocompatibility and can visualize the interaction between different organelles, which has attracted much attention. In addition, these probes can also be used to detect small molecules in the organelle environment, such as active sulfur species (RSS), reactive oxygen species (ROS), pH, viscosity and so on. However, the review of dual/multi-organelle-targeted fluorescent probe for small organic molecules lacks a systematic summary, which may hinder the development of this field. In this review, we will focus on the design strategies and bioimaging applications of dual/multi-organelle-targeted fluorescent probe, and classify them into six classes according to different organelles targeted. The first class probe targeted mitochondria and lysosome. The second class probe targeted endoplasmic reticulum and lysosome. The third class probe targeted mitochondria and lipid droplets. The fourth class probe targeted endoplasmic reticulum and lipid droplets. The fifth class probe targeted lysosome and lipid droplets. The sixth class multi-targeted probe. The mechanism of these probes targeting organelles and the visualization of the interaction between different organelles are emphasized, and the prospect and future development direction of this research field are prospected. This will provide a systematic idea for the development and functional research of dual/multi-organelle-targeted fluorescent probe, and promote its research in related physiological and pathological medicine field in the future.

A New Strategy: Distinguishable Multi-substance Detection, Multiple Pathway Tracing Based on a New Site Constructed by the Reaction Process and Its Tumor Targeting.

In recent years, it has become a trend to employ organic molecular fluorescent probes with multireaction sites for the distinguishable detection and biological imaging of similar substances. However, the introduction of multireaction sites brought great challenges to organic synthesis, and at the same time, often destroyed the conjugated structure of the molecules, leading to an unsatisfactory fluorescence emission wavelength not conducive to practical application. As the eternal theme of life, metabolism goes on all the time. Metabolism is a series of ordered chemical reactions that occurs in the organism to maintain life. Chemical reactions in metabolism can be summarized as metabolic pathways. Simultaneous monitoring of different metabolic pathways of the same substance poses a lofty challenge to the probe. Here, we developed a new strategy: to construct new sites through the preliminary reactions between probes and some targets, which can be used to further distinguish among targets or detect their metabolites, so as to realize the simultaneous visualization tracer of multiple metabolic pathways. By intravenous injection, it revealed that the probe containing benzopyrylium ion can target tumors efficiently, and thiols are highly expressed in tumors compared to other tissues (heart, lung, kidney, liver, etc.). The consumption of thiols by the probe could not prevent tumor growth, suggesting that the tumor cure was not correlated with thiol concentration. The construction of new sites in the reaction process is a novel idea in the pursuit of multiple reaction sites, which will provide more effective tools for solving practical problems.

Covalent Immobilization of Polypeptides on Polylactic Acid Films and Their Application to Fresh Beef Preservation.

To enhance the advantage of a long-term stability and low-toxicity active packaging system, two biodegradable covalent immobilized antibacterial packaging films were developed and applied to fresh beef preservation in this study. A polylactic acid (PLA) film was prepared by the extrusion-casting method. The surface of the PLA film was modified with plasma treatment to generate carboxylic acid groups, and then antibacterial agent nisin or ε-poly lysine (ε-PL) was covalently attached to the modified film surface. Physical, chemical, and antimicrobial properties of films were then characterized. Scanning electron microscopy and water contact angle images confirmed that nisin or ε-PL was successfully grafted onto the film surface. The values of protein loading on the nisin-g-PLA film and ε-PL-g-PLA film were 5.34 ± 0.26 and 3.04 ± 0.25 µg of protein/cm2 on the surface. Microbial analysis indicated that the grafted films effectively inhibit the growth of bacteria. Finally, the effects of the nisin-g-PLA film or ε-PL-g-PLA film on physicochemical changes and microbiological counts of fresh beef during cold storage at 4 °C were investigated. The total viable count of the control sample exceeded 7 logarithms of the number of colony forming units per gram (log CFU/g) after 11 days of cold storage (7.01 ± 0.14 log CFU/g) versus 15 days for the ε-PL-g-PLA film (7.37 ± 0.06 log CFU/g) and the nisin-g-PLA film (6.83 ± 0.10 log CFU/g). The results showed that covalent immobilized antibacterial packaging films had positive impacts on the shelf life and quality of fresh beef. Therefore, a covalent immobilized antibacterial packaging system could be a novel preservative method for foods.

Synthesis and Anti-HCV Activity of Sugar-Modified Guanosine Analogues: Discovery of AL-611 as an HCV NS5B Polymerase Inhibitor for the Treatment of Chronic Hepatitis C.

Chronic hepatitis C (CHC) is a major liver disease caused by the hepatitis C virus. The current standard of care for CHC can achieve cure rates above 95%; however, the drugs in current use are administered for a period of 8-16 weeks. A combination of safe and effective drugs with a shorter treatment period is highly desirable. We report synthesis and biological evaluation of a series of 2',3'- and 2',4'-substituted guanosine nucleotide analogues. Their triphosphates exhibited potent inhibition of the HCV NS5B polymerase with IC50 as low as 0.13 µM. In the HCV replicon assay, the phosphoramidate prodrugs of these analogues demonstrated excellent activity with EC50 values as low as 5 nM. A lead compound AL-611 showed high levels of the nucleoside 5'-triphosphate in vitro in primary human hepatocytes and in vivo in dog liver following oral administration.

Synthesis and Anti-HCV Activities of 4'-Fluoro-2'-Substituted Uridine Triphosphates and Nucleotide Prodrugs: Discovery of 4'-Fluoro-2'- C-methyluridine 5'-Phosphoramidate Prodrug (AL-335) for the Treatment of Hepatitis C Infection.

We report the synthesis and biological evaluation of a series of 4'-fluoro-2'- C-substituted uridines. Triphosphates of the uridine analogues exhibited a potent inhibition of hepatitis C virus (HCV) NS5B polymerase with IC50 values as low as 27 nM. In an HCV subgenomic replicon assay, the phosphoramidate prodrugs of these uridine analogues demonstrated a very potent activity with EC50 values as low as 20 nM. A lead compound AL-335 (53) demonstrated high levels of the nucleoside triphosphate in vitro in primary human hepatocytes and Huh-7 cells as well as in dog liver following a single oral dose. Compound 53 was selected for the clinical development where it showed promising results in phase 1 and 2 trials.

Matrix isolation infrared spectra, assignment and DFT investigation on reactions of iron and manganese monoxides with CH3Cl.

The reactions of iron and manganese monoxide molecules (FeO, and MnO) with monochloromethane in solid argon have been studied by matrix isolation infrared spectroscopy and quantum chemistry calculations. When annealing, the reactions of FeO and MnO with CH3Cl first form the OM-(η(Cl)-CH3Cl) (MMn, Fe) complexes, which can isomerize to CH3MOCl (MMn, Fe) upon 300<λ<580 nm irradiation. The products were characterized by isotopic IR studies with CD3Cl and (13)CH3Cl and density functional calculations. Based on theoretical calculations, the OFe-(η(Cl)-CH3Cl) and OMn-(η(Cl)-CH3Cl) complexes have (5)A' and (6)A' ground state with Cs symmetry, respectively. The accurate CCSD(T) single point calculations illustrate the CH3MOCl isomerism are 13.8 and 3.1 kcal/mol lower in energy than the OM-(η(Cl)-CH3Cl) (MMn, Fe) complexes.

Preparation and characterization of the agostic bonding molecules between metal and chlorine from the reactions of niobium and tantalum monoxide and dioxide molecules with monochloromethane in solid argon.

Reactions of niobium and tantalum monoxide and dioxide molecules with monochloromethane in solid argon have been investigated by infrared absorption spectroscopy and density functional theoretical calculations. The results show that the ground-state MO(x) (M = Nb, Ta, x = 1, 2) molecules react with CH(3)Cl to form the weakly bound MO(CH(3)Cl) and MO(2)(CH(3)Cl) complexes. The MO(CH(3)Cl) complexes rearrange to the more stable CH(2)ClM(O)H isomer upon visible light excitation, whereas the MO(2)(CH(3)Cl) complexes isomerize to the more stable CH(2)ClM(O)OH molecules under ultraviolet light irradiation. The CH(2)ClM(O)H and CH(2)ClM(O)OH molecules were predicted to involve agostic interactions between the chlorine atom and the metal center.

Matrix isolation infrared spectroscopic and density functional theoretical study of the reactions of scandium and yttrium monoxides with monochloromethane.

Reactions of scandium and yttrium monoxide molecules (ScO and YO) with monochloromethane have been studied in solid argon by infrared absorption spectroscopy and density functional theoretical calculations. The metal monoxide molecules were prepared by laser-evaporation of bulk metal oxide targets. The results show that the ground state scandium and yttrium monoxide molecules reacted with CH(3)Cl to form two MO(CH(3)Cl) (M = Sc, Y) complex isomers spontaneously on annealing. Broad-band UV-visible irradiation initiated the addition of the Cl-C bond to the M=O bond to form the CH(3)OMCl molecule and the addition of the C-H bond to the M=O bond to give the CH(2)ClMOH isomer, both of which are more stable than the MO(CH(3)Cl) complex structures. The CH(2)ClMOH molecule was predicted to involve agnostic interaction between the chlorine atom and the metal atom.