A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy

The investigation of the mode and time course of the activation of G-protein-coupled receptors (GPCRs), in particular muscarinic acetylcholine (mACh or M) receptors, is still in its infancy despite the tremendous therapeutic relevance of M receptors and GPCRs in general. We herein made use of a dualsteric ligand that can concomitantly interact with the orthosteric, that is, the neurotransmitter, binding site and an allosteric one. We synthetically incorporated a photoswitchable (photochromic) azobenzene moiety. We characterized the photophysical properties of this ligand called BQCAAI and investigated its applicability as a pharmacological tool compound with a set of FRET techniques at the M₁ receptor. BQCAAI proved to be an unprecedented molecular tool; it is the first photoswitchable dualsteric ligand, and its activity can be regulated by light. We also applied BQCCAI to investigate the time course of several receptor activation processes.     

Surface site density and utilization of platinum group metal (PGM)-free Fe–NC and FeNi–NC electrocatalysts for the oxygen reduction reaction

Pyrolyzed iron-based platinum group metal (PGM)-free nitrogen-doped single site carbon catalysts (Fe–NC) are possible alternatives to platinum-based carbon catalysts for the oxygen reduction reaction (ORR). Bimetallic PGM-free M₁M₂–NC catalysts and their active sites, however, have been poorly studied to date. The present study explores the active accessible sites of mono- and bimetallic Fe–NC and FeNi–NC catalysts. Combining CO cryo chemisorption, X-ray absorption and ⁵⁷Fe Mössbauer spectroscopy, we evaluate the number and chemical state of metal sites at the surface of the catalysts along with an estimate of their dispersion and utilization. Fe L_3,2-edge X-ray adsorption spectra, Mössbauer spectra and CO desorption all suggested an essentially identical nature of Fe sites in both monometallic Fe–NC and bimetallic FeNi–NC; however, Ni blocks the formation of active sites during the pyrolysis and thus causes a sharp reduction in the accessible metal site density, while with only a minor direct participation as a catalytic site in the final catalyst. We also use the site density utilization factor, ϕ_{SDsurface/bulk}, as a measure of the metal site dispersion in PGM-free ORR catalysts. ϕ_{SDsurface/bulk} enables a quantitative evaluation and comparison of distinct catalyst synthesis routes in terms of their ratio of accessible metal sites. It gives guidance for further optimization of the accessible site density of M–NC catalysts.

The gravimetric surface density and ORR catalytic turnover frequency of Fe–NC and Fe/Ni–NC catalysts were investigated. Both catalysts feature chemically identical Fe sites, but the presence of Ni lowered the gravimetric surface density of Fe sites.     

Evolution of the “knitting pattern” morphology in ABC triblock copolymers

A new morphology of ternary ABC triblock copolymers is presented which results from the asymmetric interaction between a centre block (poly(ethylene-co-butene)) to different end blocks (polystyrene and poly(methyl methacrylate)). This morphology with the appearance of a “knitting pattern” can be described as an intermediate of a morphology of A, B and C lamellae and a morphology of A and C lamellae with B cylinders at the A/C interface.     

Small angle neutron scattering in Al?Cu?Mg alloys

The structure changes proceeding in AlCu 2.1 at.% Mg(x) alloys with magnesium concentration form 0 to 1.2 at.% at room temperature and 100 °C are followed by small-angle neutron investigation. The results are fitted on different models. The most important result is that with increase of the Mg contents clearly a growth of the thickness opposite to the growth of the growth of the diameter to discern. The results give a good idea of the formation of GPZI(Mg) with the adequate portion of magnesium in the AlCuMg(x)-alloys and their transition to GPZII(Mg) respectively θ″ (Mg).     

Liposome delivered and polymeric metal complexes as potential sensitizers for the photodynamic therapy of cancer

Different possibilities of macromolecular metal complexes as photosensitizers (PS) for their potential use in the photodynamic therapy of cancer are described. The prepared metal porphyrazin derivatives (metals: Zn(II), Si(IV)(X)₂) exhibit long wavelength absorption and high singlet oxygen quantum yields under irradiation. One possibility is the incorporation of the PSs in liposomal vesicles giving hydrophobic conjugates with low densitiy proteins in the serum after injection. Good tumor accumulation and photodynamic activities are observed. Increased tumor uptake is also known for Pcs covalently connected via the ligand to poly(ethylene glycol monomethyl ether). New compounds contain the hydrophilic polymer at axial substituents of Si(X)₂Pc and Si(X)₂Nc. Some newly synthesized compounds with only one functional group exhibit the possibility of coupling to macromolecules like e.g. monoclonal antibodies.