Yanfei Qi

Broad-Spectrum Antiviral Property of Polyoxometalate Localized on a Cell Surface

Cs2K4Na[SiW9Nb3O40] has broad antiviral ability including anti-Influenza A, -Influenza B, -HSV-1, -HSV-2, -HIV-1, and -HBV. A series of antivirus and/or biochemical experiments and X-ray nanotomography analysis confirm that this kind of broad-spectrum antiviral property is mainly due to its localization on the cell surface.

Optimizing Colorimetric Assay Based on V2O5 Nanozymes for Sensitive Detection of H2O2 and Glucose

Nanozyme-based chemical sensing is a rapidly emerging field of research. Herein, a simple colorimetric assay for the detection of hydrogen peroxide and glucose based on the peroxidase-like activity of V2O5 nanozymes has been established. In this assay, the effects of pH, substrate, nanozyme concentrations and buffer solution have been investigated. It was found that compared with 3,3′,5,5′-tetramethylbenzidine (TMB), the enzyme substrate o-phenylenediamine (OPD) seriously interfered with the H2O2 detection. Under the optimal reaction conditions, the resulting sensor displayed a good response to H2O2 with a linear range of 1 to 500 μM, and a detection limit of 1 μM at a signal-to-noise ratio of 3. A linear correlation was established between absorbance intensity and concentration of glucose from 10 to 2000 μM, with a detection limit of 10 μM. The current work presents a simple, cheap, more convenient, sensitive, and easy handling colorimetric assay.

Synthesis, characterization and biological activity of a niobium-substituted-heteropolytungstate on hepatitis B virus.

Abstract To synthesise and characterize the polyoxometalate Cs2K4Na[SiW9Nb3O40]·H2O 1 for its anti-hepatitis B virus (HBV) properties by using the HepG2.2.15 cell. The methylthiazol tetrazolium assay was used to evaluate the growth inhibitory effect of Compound 1 on HepG2.2.15 cell. By using ELISA and real-time PCR, respectively, the presence of extracellular hepatitis B surface antigen (HBsAg), e antigen (HBeAg), and HBV DNA were measured. The levels of intracellular HBV DNA and mRNA were determined by using Southern blot or reverse-transcription-PCR, respectively. Intracellular distribution of antigen were measured by Western blot. A 1995μmol/L concentration of the commercially-available hepatitis B drug, adefovir dipivoxil (ADV), was required to achieve 50% cytotoxicity against cultured cells (CC50) by day nine; in contrast, only 1747μmol/L of Compound 1 was required for the same result. Treatment of HepG2.2.15 cells with Compound 1 effectively suppress the secretion of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. IC50 values were determined to be 80μmol/L for HBsAg, 75μmol/L for HBeAg and 3.72μmol/L for supernatant HBV DNA at day nine post-exposure, as opposed to 266, 296, 30.09μmol/L, respectively, for ADV. Intracellular HBV DNA, mRNA and antigen were also found to be decreased by Compound 1. The same dose of ADV yielded a significantly less robust inhibitory effect. Compound 1 can clear HBV from hepatic cells and may represent a therapeutic agent to treat HBV infection.

Inhibition of hepatitis C virus infection by polyoxometalates.

Hepatitis C virus (HCV) infects about 2% of the world population. The standard treatment of chronic HCV infection is still discontented because of the low sustained virological response rate. The development of new HCV antivirals is a healthcare imperative. We explored the potentials of polyoxometalates to inhibit HCV infection using newly developed HCVcc cell culture system. We found one polyoxometalate compound (named POM-12) can inhibit HCV infection at the nanomolar range while displayed little cytotoxicity. We showed that POM-12 inhibited pseudotyped HCV infection but had no effect on HCV RNA replication. Furthermore, we showed that POM-12 was virucidal and can disrupt HCV particles. Finally we demonstrated that POM-12 had no effect on the vesicular stomatitis virus infection while had weak inhibitory activity against the influenza virus infection. In conclusion, we identified a potent anti-HCV compound which may provide an attractive drug candidate to cure HCV infection.

BSA-binding properties and anti-proliferative effects of amino acids functionalized polyoxomolybdates

Glycine decorated heteropolymolybdates, K2Na[AsMo6O21(O2CCH2NH3)3]·6H2O 1 and K2Na2[γ-Mo8O26(O2CCH2NH3)2]·6H2O 2, have been synthesized and evaluated for in vitro anti-proliferative effects. The identity and high purity of compounds 1 and 2 were confirmed by elemental analysis, FT-IR spectrum, UV-vis spectrum, and X-ray diffraction. Crystal data for 2: triclinic, P-1, a=9.792(2)Å, b=10.077(2)Å, c=10.351(2)Å, α=83.865(4)°, β=71.110(4)°, γ=62.284(3)°, V=854.3(3)Å(3), Z=1, R(final)=0.0486. The inhibitory effects of 1 and 2 on human non-small cell lung cancer cell line A549 were investigated by MTT assay, nuclear staining, and the flow cytometry. It indicated that compound 1 inhibited the proliferation of A549 cells in a dose-dependent and time-dependent manner, which is more effective than the positive control, 5-fluorouracil (5-FU) (P<0.05). The staining and flow cytometry results showed that compound 1 induced the apoptosis and necrosis of A549 cells and inhibit cell proliferation, which is associated with S-phase arrest. Compound 2 showed a modest activity in a dose-dependent manner. In addition, the interaction between compound 1 and bovine serum albumin (BSA) was evaluated by spectroscopic methods. The results showed that the compound 1 effectively quenched the intrinsic fluorescence of BSA via static quenching and changed the conformation of BSA.

Luminescent hybrid metal-organic coordination polymers based on Cu/Ag-bis(benzotriazole) units and polyoxometalates

Abstract The reaction of polyoxometalate (NH4)6[Mo7O24], transition-metal ions (Cu2+ or Ag+), and a bridging ligand (bbtx) in the hydrothermal environment led to two hybrid coordination polymers, [Cu(bbtx)3][Mo6O19] (1) and [Ag2(bbtx)2][Mo6O19] (2). Luminescent measurements suggest that 1 mainly exhibits luminescent emission of bbtx, but 2 displays strong emission bands ascribed to the ligand-to-metal charge transfer. Compound 2 also shows reversible thermochromic luminescence from 300 K–77 K–300 K. Introduction of [Mo6O19]2− into the Ag-bbtx network can lead to luminescent quench of 2 under irradiation of 300 W Xe light, due to reduction of Ag(I) into Ag(0) with breaking of Ag–N bonds of 2. The relevant mechanism was investigated by Powder X-ray diffraction and X-ray photoelectron spectrum , and the irradiated 2 was used as a catalyst for reduction of p-nitrophenol with good catalytic activity.

Pharmacokinetics of Anti-HBV Polyoxometalate in Rats

Polyoxometalates are non-nucleoside analogs that have been proven to exhibit broad-spectrum antiviral activity. In particular, Cs2K4Na[SiW9Nb3O40].H2O 1 shows low toxicity and high activity against HBV. The preclinical pharmacokinetics of Compound 1 in rats were characterized by establishing and applying inductively coupled plasma-mass spectrometry method to determine the concentration of W in plasma, urine, feces, bile and organ samples. The quantitative ICP-MS method demonstrated good sensitivity and application in the pharmacokinetics study of polyoxometalates. The pharmacokinetic behavior of Compound 1 after intravenous or oral administration fit a two-compartment model. Tmax ranges from 0.1 h to 3 h and the T1/2 of Compound 1 is between 20 h and 30 h. The absolute bioavailability of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93%, respectively. The rates of plasma protein binding of Compound 1 at 9, 18 and 36 mg/ml of Compound 1 are 62.13±9.41%, 71.20±24.98% and 49.00±25.59%, respectively. Compound 1 was widely distributed throughout the body, and high levels of compound 1 were found in the kidney and liver. The level of Compound 1 in excretion was lower: 30% for urine, 0.28% for feces and 0.42% for bile, respectively. For elaborate pharmacokinetic characteristics to be fully understood, the metabolism of Compound 1 needs to be studied further.

In vitro anti-hepatitis B and SARS virus activities of a titanium-substituted-heteropolytungstate

Abstract A structural determined heteropolytungstate, [K4(H2O)8Cl][K4(H2O)4PTi2W10O40]·NH2OH 1, has been synthesized and evaluated for in vitro antiviral activities against hepatitis B (HBV) and SARS virus. The identity and high purity of compound 1 were confirmed by elemental analysis, NMR, IR analysis and single-crystal X-ray diffraction. The compound 1, evaluated in HepG 2.2.15 cells expressing permanently HBV, significantly reduced the levels of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. EC50 values were determined to be 54μM for HBeAg, 61μM for HBsAg and 2.66μM for supernatant HBV DNA, as compared to 1671, 1570, 169μM, respectively, for the commercially-available hepatitis B drug adefovir dipivoxil (ADV). Intracellular cccDNA, pgRNA and HBcAg were also found to be decreased by compound 1 in a concentration-dependent manner. Cytotoxicity results showed that compound 1 has low toxicity in HepG 2 cells with CC50 value of 515.20μM. The results indicate that compound 1 can efficiently inhibit HBV replication in HepG 2.2.15 cells line in vitro. Additionally, compound 1 also shows high anti-SARS activity at an EC50 of 7.08μM and toxicity with a CC50 of 118.6μM against MDCK cells.

Influence of VO2 Nanoparticle Morphology on the Colorimetric Assay of H2O2 and Glucose

Nanozyme-based colorimetric sensors have received considerable attention due to their unique properties. The size, shape, and surface chemistry of these nanozymes could dramatically influence their sensing behaviors. Herein, a comparative study of VO2 nanoparticles with different morphologies (nanofibers, nanosheets, and nanorods) was conducted and applied to the sensitive colorimetric detection of H2O2 and glucose. The peroxidase-like activities and mechanisms of VO2 nanoparticles were analyzed. Among the VO2 nanoparticles, VO2 nanofibers exhibited the best peroxidase-like activity. Finally, a comparative quantitative detections of H2O2 and glucose were done on fiber, sheet, and rod nanoparticles. Under the optimal reaction conditions, the lower limit of detection (LOD) of the VO2 nanofibers, nanosheets, and nanorods for H2O2 are found to be 0.018, 0.266, and 0.41 mM, respectively. The VO2 nanofibers, nanosheets, and nanorods show the linear response for H2O2 from 0.025–10, 0.488–62.5, and 0.488–15.625 mM, respectively. The lower limit of detection (LOD) of the VO2 nanofibers, nanosheets, and nanorods for glucose are found to be 0.009, 0.348, and 0.437 mM, respectively. The VO2 nanofibers, nanosheets, and nanorods show the linear response for glucose from 0.01–10, 0.625–15, and 0.625–10 mM, respectively. The proposed work will contribute to the nanozyme-based colorimetric assay.

Antileukemic activity of an arsenomolybdate in the human HL-60 and U937 leukemia cells

The antileukemic activity, mechanisms and serum albumin interactions of an arsenomolybdate, K2Na[AsMo6O21(O2CCH2NH3)3]·6H2O (1), was evaluated in the human leukemia HL-60 and U937 cells. The results indicated that 1 could inhibit the proliferation of both leukemia cell lines in a dose-dependent manner with the 50% lethal concentration (IC50) value of 8.61μM for HL-60 and 14.50μM for U937 at 24h, compare to the positive controls, all-trans retinoic acid (ATRA) with IC50 value of 20.76μM and 14.85μM,and As2O3 with IC50 value of 6.40μM and 8.75μM at 24h, respectively (P<0.05). Furthermore, the anti-leukemia activity of compound 1 might be medicated by arresting the leukemic cells in the G1 phase and inducing apoptosis via caspase-3 and bcl-2 regulatory proteins. Spectroscopic techniques results showed that the fluorescence of human serum albumin was quenched by compound 1, and the quenching mechanism was mainly static quenching. Compound 1 might be a potential medicinal candidate against acute promyelocytic leukemia.