Hydrogel Membrane Improves Batch‐to‐Batch Reproducibility of an Enzymatic Glucose Biosensor

A permselective membrane is a critical component that defines the linear detection limits, the sensitivity, and thus the ultimate efficacy of an enzymatic biosensor. Although membranes like epoxy‐polyurethane (epoxy‐PU) and Nafion are widely used and provide the desired glucose detection limits of 2 to 30 mM, both the within batch and batch‐to‐batch variability of sensors that use these materials is a concern. The hypothesis for this study was that a crosslinked hydrogel would have a sufficiently uniform porosity and hydrophilicity to address the variability in sensor sensitivity. The hydrogel was prepared by crosslinking di‐hydroxyethyl methacrylate, hydroxyethyl methacrylate and N‐vinyl pyrrolidone with 2.5 mol% ethylene glycol dimethacrylate using water soluble initiators – ammonium persulfate and sodium metabisulfite under a nitrogen atmosphere. The hydrogel was applied to the sensor by dip coating during polymerisation. Electrochemical measurements revealed that the response characteristics of sensors coated with this membrane are highly consistent. Scanning electrochemical microscopy (SECM) was used to spatially resolve glucose diffusion through the membrane by measuring the consequent H₂O₂ release and compared with an epoxy‐PU membrane. Hydrogen peroxide measurements using SECM revealed that the epoxy‐PU membranes had uneven lateral diffusion profiles compared to the uniform profile of the hydrogel membranes. The uneven diffusion profiles of epoxy‐PU membranes are attributed to a fabrication method that results in uneven membrane properties, while the uniform diffusion profiles of the hydrogel membranes are primarily dictated by their uniform pore size.     

Solid-phase synthesis of BODIPY dyes and development of an immunoglobulin fluorescent sensor

The diversification of the BODIPY scaffold has been hindered by its controversial adaptability to solid-phase chemistry. Herein we report the first solid-phase synthesis of a BODIPY library in high purities. We screened the library against a set of proteins, identified an immunoglobulin fluorescent sensor (Ig Orange) and confirmed its binding by SPR experiments.     

Room temperature ferromagnetism in undoped and Fe doped ZnO nanorods: Microwave-assisted synthesis

One-dimensional (1D) undoped and Fe doped ZnO nanorods of average length ∼1 μm and diameter ∼50 nm have been obtained using a microwave-assisted synthesis. The magnetization (M) and coercivity (H_c) value obtained for undoped ZnO nanorods at room temperature is ∼5×10⁻³ emu/g and ∼150 Oe, respectively. The Fe doped ZnO samples show significant changes in M -H loop with increasing doping concentration. Both undoped and Fe doped ZnO nanorods exhibit a Curie transition temperature (T_c) above 390 K. Electron spin resonance and Mössbauer spectra indicate the presence of ferric ions. The origin of ferromagnetism in undoped ZnO nanorods is attributed to localized electron spin moments resulting from surface defects/vacancies, where as in Fe doped samples is explained by F center exchange mechanism.     

Sc(OTf)3-catalyzed sugar based tandem ene-Prins cyclization: a novel synthesis of hexahydro-2H-furo[3,2-b]pyranopyran scaffolds

Ttandem ene-Prins cyclization between an aldehyde and an olefin tethered sugar aldehyde has been achieved using a catalytic amount of scandium triflate (10 mol %) at ambient temperature to give a novel series of sugar annulated pyranopyran derivatives in good yields with high selectivity. This is the first report on sugar based ene-Prins cyclization between an aldehyde and O-prenyl derivative of a sugar aldehyde.     

Aryl Extensions of Thienopyrimidinones as Fibroblast Growth Factor Receptor 1 Kinase Inhibitors

Optimization of thienopyrimidinone derivatives as FGFR1 kinase inhibitors is being pursued. The present results confirm predictions of computational modeling that an aryl substituent can be introduced at the 2-position in structure 3. The substituent is anticipated to project deeper into the binding site and provide opportunities for enhanced activity and selectivity. The most potent analog reported herein, 13, has a 4-hydroxyphenyl substituent and yields an IC₅₀ of 6 μM for inhibition of phosphorylation by FGFR1 kinase. It was also found that the western anisole-containing substituent in 3 can be replaced by a propionic acid group with no loss in potency and with potentially significant gains in pharmacologically relevant properties.     

Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay

The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with the liquid chromatography-mass spectrometry method, this method has shown to be a fast and cost-effective way to perform CYP inhibition studies. The results indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6, with apparent half-maximal inhibitory concentration (IC(50)) values of 0.78 μg/mL and 0.636 μg/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC(50) of 39 μg/mL, and weak inhibition was detected for CYP2C19. The IC(50) of CYP2C19 could not be determined, however, because inhibition was <50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition assay, whereas non-competitive inhibition was shown in inhibition assays using CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4), tranylcypromine (CYP2C19) and furafylline (CYP1A2) were ACCESSused as positive controls throughout the experiments. This study shows that MSE may contribute to an herb-drug interaction if administered concomitantly with drugs that are substrates for CYP3A4, CYP2D6 and CYP1A2.     

Mechanistic investigations on the efficient catalytic decomposition of peroxynitrite by ebselen analogues

In this study, ebselen and its analogues are shown to be catalysts for the decomposition of peroxynitrite (PN). This study suggests that the PN-scavenging ability of selenenyl amides can be enhanced by a suitable substitution at the phenyl ring in ebselen. Detailed mechanistic studies on the reactivity of ebselen and its analogues towards PN reveal that these compounds react directly with PN to generate highly unstable selenoxides that undergo a rapid hydrolysis to produce the corresponding seleninic acids. The selenoxides interact with nitrite more effectively than the corresponding seleninic acids to produce nitrate with the regeneration of the selenenyl amides. Therefore, the amount of nitrate formed in the reactions mainly depends on the stability of the selenoxides. Interestingly, substitution of an oxazoline moiety on the phenyl ring stabilizes the selenoxide, and therefore, enhances the isomerization of PN to nitrate.     

Design, synthesis and biological evaluation of choline based SPECT imaging agent: Ga(III)-DO3A-EA-Choline

The enhanced choline uptake and phosphorylation in tumor cells has motivated the development of radiolabeled choline derivatives as diagnostic markers for imaging cell membrane proliferation and noninvasive detection of prostate, brain and breast tumors. In the present work, we report a facile strategy for the synthesis of choline functionalized macrocyclic chelating agent (DO3A-EA-choline) and its radiocomplexation with (67)Ga for potential tumor imaging applications. The synthesis of the desired compound featured quaternization of N,N-dimethylaminoethanol with 1,2-dibromoethane followed by subsequent alkylation with trisubstituted cyclen (DO3A). All intermediates and final compounds have been fully characterized by spectroscopic techniques, namely, (1)H, (13)C NMR and mass spectroscopy. The compound has been successively labeled with (67)Ga-citrate in ammonium acetate buffer (pH 6.5) at 80 °C. MTT assays have been performed on the HEK cell line to determine the cytotoxicity of the compound. Cell uptake studies carried out on the U-87 MG cell line exhibited saturable binding of the radioconjugate in picomolar range with a K(d) value of 0.528 pM. The in vivo biodistribution and blood kinetics studies exhibited rapid clearance of the radiolabeled complex and excretion through the renal and hepatobiliary route. The present studies demonstrate the potential applications of (67)Ga-DO3A-EA-choline as a radiopharmaceutical for molecular imaging using ((67/68)Ga) SPECT and PET modalities.