Generic nitric oxide (NO) generating surface by immobilizing organoselenium species via layer-by-layer assembly

A universal nitric oxide (NO) generating surface is assembled via Layer-by-Layer (LbL) deposition of sodium alginate (Alg) and organoselenium modified polyethyleneimine (SePEI) on quartz and polymeric substrates. The immobilized SePEI species is capable of catalytically decomposing S-nitrosothiol species (RSNO) to NO in the presence of thiol reducing agents (e.g., glutathione, cysteine, etc.). The stepwise buildup of the multilayer films is monitored by UV-vis spectroscopy, SEM and surface contact angle measurements. X-ray photoelectron spectroscopy is used to study the stoichiometry between the polyanion and polycation, and also the presence of Se in the catalytic LbL film. A reductive annealing process is necessary to improve the stability of freshly coated multilayer films via chain rearrangement. Chemiluminescence measurements illustrate the ability of the LbL films to generate NO from S-nitrosoglutathione (GSNO) in the presence of glutathione (GSH). Enhanced NO fluxes can be achieved by increasing the number of catalytic (SePEI/Alg) bilayers coated on the substrates. Nitric oxide generation is observed even after prolonged contact with sheep whole blood. Preliminary applications of this LbL on silicone rubber tubings and polyurethane catheters reveal similar NO generation behavior from these biomedical grade polymeric substrates.     

A Covalent Binding Mode of a Pyrazole-Based CD38 Inhibitor

Brain concentrations of nicotinamide adenine dinucleotide (NAD⁺), an important cellular co-factor, tend to decrease with age and in neurodegeneration. As the NADase cluster of differentiation 38 (CD38) significantly contributes to NAD⁺ consumption, we reasoned that CD38 inhibition may be of therapeutic value for CNS disorders. The new pyrazole compound was designed based on a known CD38 inhibitor and showed good inhibitory potency. Several attempts to co-crystallise this pyrazole with CD38 and cyclic adenosine diphosphate ribose (cADPR) culminated in a high-resolution X-ray structure, in which the pyrazolyl group in the new compound formed a covalent bond with one of the ribosyl units of cADPR. This reaction proceeded under retention of configuration and resulted in a neutral ribosyl-pyrazole conjugate that is embedded within the active site of the enzyme. An analysis of this structural complex gave rise to design principles that enabled the preparation of more potent CD38 inhibitors with drug-like properties.     

Switchable electrical conductivity in a three-dimensional metal–organic framework via reversible ligand n-doping

Redox-active metal–organic frameworks (MOFs) are promising materials for a number of next-generation technologies, and recent work has shown that redox manipulation can dramatically enhance electrical conductivity in MOFs. However, ligand-based strategies for controlling conductivity remain under-developed, particularly those that make use of reversible redox processes. Here we report the first use of ligand n-doping to engender electrical conductivity in a porous 3D MOF, leading to tunable conductivity values that span over six orders of magnitude. Moreover, this work represents the first example of redox switching leading to reversible conductivity changes in a 3D MOF.

Redox-active ligands are used to reversibly tune electrical conductivity in a porous 3D metal–organic framework (MOF).     

Terpyridine-Functionalized Calixarenes: Synthesis,Characterization and Anion Sensing Applications

Lanthanide complexes have been developed and are reported herein. These complexes were derived from a terpyridine-functionalized calix[4]arene ligand, chelated with Tb³⁺ and Eu³⁺. Synthesis of these complexes was achieved in two steps from a calix[4]arene derivative: (1) amide coupling of a calix[4]arene bearing carboxylic acid functionalities and (2) metallation with a lanthanide triflate salt. The ligand and its complexes were characterized by NMR (¹H and ¹³C), fluorescence and UV-vis spectroscopy as well as MS. The photophysical properties of these complexes were studied; high molar absorptivity values, modest quantum yields and luminescence lifetimes on the ms timescale were obtained. Anion binding results in a change in the photophysical properties of the complexes. The anion sensing ability of the Tb(III) complex was evaluated via visual detection, UV-vis and fluorescence studies. The sensor was found to be responsive towards a variety of anions, and large binding constants were obtained for the coordination of anions to the sensor.     

Protected Amine Labels: A Versatile Molecular Scaffold for Multiplexed Nominal Mass and Sub-Da Isotopologue Quantitative Proteomic Reagents

We assemble a versatile molecular scaffold from simple building blocks to create binary and multiplexed stable isotope reagents for quantitative mass spectrometry. Termed Protected Amine Labels (PAL), these reagents offer multiple analytical figures of merit including, (1) robust targeting of peptide N-termini and lysyl side chains, (2) optimal mass spectrometry ionization efficiency through regeneration of primary amines on labeled peptides, (3) an amino acid-based mass tag that incorporates heavy isotopes of carbon, nitrogen, and oxygen to ensure matched physicochemical and MS/MS fragmentation behavior among labeled peptides, and (4) a molecularly efficient architecture, in which the majority of hetero-atom centers can be used to synthesize a variety of nominal mass and sub-Da isotopologue stable isotope reagents. We demonstrate the performance of these reagents in well-established strategies whereby up to four channels of peptide isotopomers, each separated by 4 Da, are quantified in MS-level scans with accuracies comparable to current commercial reagents. In addition, we utilize the PAL scaffold to create isotopologue reagents in which labeled peptide analogs differ in mass based on the binding energy in carbon and nitrogen nuclei, thereby allowing quantification based on MS or MS/MS spectra. We demonstrate accurate quantification for reagents that support 6-plex labeling and propose extension of this scheme to 9-channels based on a similar PAL scaffold. Finally, we provide exemplar data that extend the application of isotopologe-based quantification reagents to medium resolution, quadrupole time-of-flight mass spectrometers.

Silica aerogel–poly(ethylene‐co‐vinyl acetate) composite for transparent heat retention films

Poly(ethylene‐co‐vinyl acetate) (EVA) plastic films are widely used for solar coverings including photovoltaic modules and commercial greenhouse films, but are poor at controlling heat flow. In this work, silica aerogel (SA) nanogels were examined for preparing transparent heat retention EVA films that block far infrared spectra radiation to maintain heat, without compromising the optical performance of the films. SA nanogels were melt‐mixed using a mini twin‐screw extruder with EVA pellets to form SA/EVA composite, which were pressed into thin films with controlled thickness. The composite films were characterized in terms of optical properties using a variety of analytical methods including FTIR, UV–Vis spectroscopy, electron, confocal, and atomic force microscopy. Both thermicity and thermal conductivity of commercial and experimental SA/EVA films were measured. The results demonstrated that the SA/EVA films gave improved infrared retention compared to commercial thermal plastic films without compromising visible light transmission, showing the potential for this approach in next generation heat retention films. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 927–935     

A simple zero length surface-modification approach for preparing novel bifunctional supports for co-immobilisation studies

A straightforward method of creating a bifunctional support possessing pre-defined ratios of amine and chloromethyl groups based upon a controlled conversion of standard Merrifield resin is presented. It avoids the extensive optimisation of reactant concentrations and reaction conditions required by existing methods. Furthermore, it avoids increases in the spacer/linker length that lead to detrimental reductions in the rigidity of the grafted layer. The method will allow for efficient, predictable and reproducible co-immobilisation of molecular species.