Mesomorphic properties of cyanobiphenyl dimers with a central malonate unit

A series of cyanobiphenyl dimers attached via alkoxy spacers to a central malonate were prepared, and the mesomorphic behaviour was studied by differential scanning calorimetry (DSC), polarised optical microscopy and X-ray diffraction (Wide-angle X-ray scattering and Small-angle X-ray scattering). Depending on spacer lengths and substitution of the malonate, nematic and smectic A mesophases with pronounced odd–even effect were observed. C-2-unsubstituted malonates formed nematic phases for chain lengths C₆–C₁₄, while C₁₂ and C₁₄ homologues displayed additional smectic A phases. In contrast, malonates with fluorinated tails at C-2 displayed exclusively smectic A phases. Remarkably, the X-ray diffraction profile of the smectic A phase of the C-2-unsubstituted C₁₂ malonate showed a fundamental (001) and the corresponding third-order (003) diffraction peak, but no (002) reflection. Using Fourier analysis, the diffraction pattern was converted to an electron density profile, which was in good agreement with the proposed packing model of the SmA mesophase based on a horseshow- or hairpin-like conformation of the malonate.     

Using physics-based pose predictions and free energy perturbation calculations to predict binding poses and relative binding affinities for FXR ligands in the D3R Grand Challenge 2

Computer-aided drug design has become an integral part of drug discovery and development in the pharmaceutical and biotechnology industry, and is nowadays extensively used in the lead identification and lead optimization phases. The drug design data resource (D3R) organizes challenges against blinded experimental data to prospectively test computational methodologies as an opportunity for improved methods and algorithms to emerge. We participated in Grand Challenge 2 to predict the crystallographic poses of 36 Farnesoid X Receptor (FXR)-bound ligands and the relative binding affinities for two designated subsets of 18 and 15 FXR-bound ligands. Here, we present our methodology for pose and affinity predictions and its evaluation after the release of the experimental data. For predicting the crystallographic poses, we used docking and physics-based pose prediction methods guided by the binding poses of native ligands. For FXR ligands with known chemotypes in the PDB, we accurately predicted their binding modes, while for those with unknown chemotypes the predictions were more challenging. Our group ranked #1st (based on the median RMSD) out of 46 groups, which submitted complete entries for the binding pose prediction challenge. For the relative binding affinity prediction challenge, we performed free energy perturbation (FEP) calculations coupled with molecular dynamics (MD) simulations. FEP/MD calculations displayed a high success rate in identifying compounds with better or worse binding affinity than the reference (parent) compound. Our studies suggest that when ligands with chemical precedent are available in the literature, binding pose predictions using docking and physics-based methods are reliable; however, predictions are challenging for ligands with completely unknown chemotypes. We also show that FEP/MD calculations hold predictive value and can nowadays be used in a high throughput mode in a lead optimization project provided that crystal structures of sufficiently high quality are available.     

Immobilization of Bovine Serum Albumin on Polytetrafluoroethylene for Application as a Potential Solid Support for Biosensor Development with Visual Detection

Immobilization of biomolecules on polymers is attractive for developing new biosensors and analytical methods. Polytetrafluoroethylene, PTFE (Teflon), is a low-cost polymer that has unique chemical and physicochemical properties. In this work, PTFE was investigated as a solid support for biosensor development. Bovine serum albumin (BSA) was immobilized directly on PTFE thin films without pretreatment. BSA was biotinylated, while the immobilization was controlled by the formation of visual spots using either streptavidin–fluorescein or streptavidin–gold nanoparticle conjugates. The visualization of the spots was accomplished by the naked eye (red spots) or a digital camera that captures the emitted fluorescence (green spots). The signal-to-background ratio was determined for both detection systems and was equal to 24.4 and 58.4 for streptavidin–fluorescein and streptavidin–gold nanoparticles, respectively.     

Producing μ−d and μ−t in vacuum

After the feasibility of vacuum isolated ^–d production was demonstrated at TRIUMF in 1989, development was begun on a target system that would take advantage of the process to aid in the understanding of the muon catalyzed fusion cycle. Minimal neutron backgrounds, the ability to use silicon detectors, and compatibility with tritium were considered important for a very versatile target system. The advantages which the target gives in isolating CF process will be outlined.     

Strongly fluorescent ethylene‐bridged poly(para‐phenylene) ladder polymers

We have synthesized novel, fully soluble ethylene‐bridged para‐phenylene ladder polymers. The synthesis of our ladder poly(dihydrophenanthrene)s (LPDPs) was achieved via an aryl‐aryl homocoupling according to Yamamoto, followed by a polymer‐analogous pinacolization with SmI₂. The resulting, strongly fluorescent polymers were characterisized by NMR, UV/Vis‐ and PL measurements.     

TEMPO/TCC as a Chemo Selective Alternative for the Oxidation of Hyaluronic Acid

Hyaluronic acid (HA)-based hydrogels are very commonly applied as cell carriers for different approaches in regenerative medicine. HA itself is a well-studied biomolecule that originates from the physiological extracellular matrix (ECM) of mammalians and, due to its acidic polysaccharide structure, offers many different possibilities for suitable chemical modifications which are necessary to control, for example, network formation. Most of these chemical modifications are performed using the free acid function of the polymer and, additionally, lead to an undesirable breakdown of the biopolymer’s backbone. An alternative modification of the vicinal diol of the glucuronic acid is oxidation with sodium periodate to generate dialdehydes via a ring opening mechanism that can subsequently be further modified or crosslinked via Schiff base chemistry. Since this oxidation causes a structural destruction of the polysaccharide backbone, it was our intention to study a novel synthesis protocol frequently applied to selectively oxidize the C6 hydroxyl group of saccharides. On the basis of this TEMPO/TCC oxidation, we studied an alternative hydrogel platform based on oxidized HA crosslinked using adipic acid dihydrazide as the crosslinker.     

A Model-Derived Global Climatology of UV Irradiation at the Earth's Surface

Abstract— We present calculations of the geographical distribution of the dose rate at the surface of UVB (280–320 nm), UVA (320–400 nm) and, using biological action spectra, the effective radiation for erythema, cataracts and keratitis. A multistream radiative transfer model is used in conjunction with a multiyear climatology of ozone, cloud, surface pressure, surface albedo, temperature and a rudimentary representation of aerosols to calculate the clear-sky and all-sky irradiances. Model outputs are evaluated using daily UV measurements and found to be accurate to about ±10% for clear skies and ±20% for all-sky conditions. The effects of UV-weighted surface albedo, surface altitude, sun-earth separation and the vertical distribution of ozone and temperature are included. The results show that the sun's position is the most important factor in determining the geographical pattern of global daily UV rather than column ozone, cloud, surface pressure, daylength or surface albedo. Over elevated regions, the effect of the differences in surface pressure on daily doses was found to be more significant than the effect of the differences in column ozone. Clouds reduce the clear-sky UV dose from a few percent over arid and semiarid regions to 45% in regions with frequent midlatitude depressions.     

Modified,Amorphous Titania—A Hybrid Semiconductor for Detoxification and Current Generation by Visible Light

Amorphous, microporous TiO ₂ hybrid semiconductors modified with transition metals induce generation of a photocurrent and photocatalytic degradation of the water contaminant 4-chlorophenol through photoinduced charge separation (the postulated mechanism is shown in the picture, Ar=4-ClC₆H₄). In contrast to the previously known crystalline titania photocatalysts, which are active only when excited with UV light, the amorphous semiconductors modified with platinum, rhodium, and gold chloride enable both processes also with visible light.