Selective syntheses of novel polyether fullerene multiple adducts

We have applied a modified macrocyclic tether approach to control multiple additions to C60. The technique of 3He NMR was used to confirm the selective formation of specific C60 multiple adducts by the macrocyclic tether approach. An oligoglycol was used as a flexible linker to produce macrocyclic polyether-linked malonates 5, 6, 8, and 9 under solid-liquid PTC (phase-transfer-catalysis) conditions. The formation of a single C60 tris-adduct, 3, from macrocyclic malonate 1 and 3He@C60 was proven by 3He NMR. Similarly, multiple additions to C60 of macrocyclic polyether malonate 5 gave C60 bis-adduct 10 selectively, while the reaction of C60 with macrocyclic malonate 8 gave bis-adducts 11 and 12. A similar process with macrocyclic malonate 6 gave tris-adduct 13 with high selectivity as well. Saponification of these C60 multiple adducts gives the corresponding polyacids that are potentially useful in biological applications. Macrocyclic polyether fullerenes are a new class of ionophores, which could be interesting for molecular recognition and for the development of biosensors.     

The Active Sites of a Rod‐Shaped Hollandite DeNOx Catalyst

The identification of catalytically active sites (CASs) in heterogeneous catalysis is of vital importance to design and develop improved catalysts, but remains a great challenge. The CASs have been identified in the low‐temperature selective catalytic reduction of nitrogen oxides by ammonia (SCR) over a hollandite manganese oxide (HMO) catalyst with a rod‐shaped morphology and one‐dimensional tunnels. Electron microscopy and synchrotron X‐ray diffraction determine the surface and crystal structures of the one‐dimensional HMO rods closed by {100} side facets and {001} top facets. A combination of X‐ray absorption spectra, molecular probes with potassium and nitric oxide, and catalytic tests reveals that the CASs are located on the {100} side facets of the HMO rods rather than on the top facets or in the tunnels, and hence semi‐tunnel structural motifs on the {100} facets are evidenced to be the CASs of the SCR reaction. This work paves the way to further investigate the intrinsic mechanisms of SCR reactions.     

Solution insights into the structure of the Efb/C3 complement inhibitory complex as revealed by lysine acetylation and mass spectrometry

The extracellular fibrinogen-binding protein (Efb), an immunosuppressive and anti-inflammatory protein secreted by Staphylococcus aureus, has been identified as a potent inhibitor of complement-mediated innate immunity. Efb functions by binding to and disrupting the function of complement component 3 (C3). In a recent study, we presented a high-resolution co-crystal structure of the complement inhibitory domain of Efb (Efb-C) bound to its cognate domain (C3d) from human C3 and employed a series of structure/function analyses that provided evidence for an entirely new, conformational change-based mechanism of complement inhibition. To better understand the Efb/C3 complex and its downstream effects on C3 inhibition, we investigated the solvent-accessibility and protein interface of Efb(-C)/C3d using a method of lysine acetylation, proteolytic digestion, and mass spectrometric analysis. Lysine modification in Efb was monitored by the mass increment of lysine-containing fragments. Besides confirming the binding sites observed in co-crystal structure study, the in-solution data presented here suggest additional contacting point(s) between the proteins that were not revealed by crystallography. The results of this study demonstrate that solution-based analysis of protein-protein interactions can provide important complementary information on the nature of protein-protein interactions.     

Discovery of novel cathepsin S inhibitors by pharmacophore-based virtual high-throughput screening

The cysteine protease cathepsin S (CatS) is involved in the pathogenesis of autoimmune disorders, atherosclerosis, and obesity. Therefore, it represents a promising pharmacological target for drug development. We generated ligand-based and structure-based pharmacophore models for noncovalent and covalent CatS inhibitors to perform virtual high-throughput screening of chemical databases in order to discover novel scaffolds for CatS inhibitors. An in vitro evaluation of the resulting 15 structures revealed seven CatS inhibitors with kinetic constants in the low micromolar range. These compounds can be subjected to further chemical modifications to obtain drugs for the treatment of autoimmune disorders and atherosclerosis.     

Persistent Room Temperature Phosphorescence from Triarylboranes: A Combined Experimental and Theoretical Study

Achieving highly efficient phosphorescence in purely organic luminophors at room temperature remains a major challenge due to slow intersystem crossing (ISC) rates in combination with effective non‐radiative processes in those systems. Most room temperature phosphorescent (RTP) organic materials have O‐ or N‐lone pairs leading to low lying (n, π*) and (π, π*) excited states which accelerate k_isc through El‐Sayed's rule. Herein, we report the first persistent RTP with lifetimes up to 0.5 s from simple triarylboranes which have no lone pairs. RTP is only observed in the crystalline state and in highly doped PMMA films which are indicative of aggregation induced emission (AIE). Detailed crystal structure analysis suggested that intermolecular interactions are important for efficient RTP. Furthermore, photophysical studies of the isolated molecules in a frozen glass, in combination with DFT/MRCI calculations, show that (σ, B p)→(π, B p) transitions accelerate the ISC process. This work provides a new approach for the design of RTP materials without (n, π*) transitions.     

Dynamics of Bacteriorhodopsin in the Dark-Adapted State from Solution Nuclear Magnetic Resonance Spectroscopy

To achieve efficient proton pumping in the light-driven proton pump bacteriorhodopsin (bR), the protein must be tightly coupled to the retinal to rapidly convert retinal isomerization into protein structural rearrangements. Methyl group dynamics of bR embedded in lipid nanodiscs were determined in the dark-adapted state, and were found to be mostly well ordered at the cytosolic side. Methyl groups in the M145A mutant of bR, which displays only 10 % residual proton pumping activity, are less well ordered, suggesting a link between side-chain dynamics on the cytosolic side of the bR cavity and proton pumping activity. In addition, slow conformational exchange, attributed to low frequency motions of aromatic rings, was indirectly observed for residues on the extracellular side of the bR cavity. This may be related to reorganization of the water network. These observations provide a detailed picture of previously undescribed equilibrium dynamics on different time scales for ground-state bR.     

Verbindungsbildung in den quasi-binären Systemen AcX4?MX2 (Ac = Th,U; M = Ca,Sr, Ba,Eu, Ge,Sn, Pb; X = Br,I)

Formation of Compounds in the Quasi-binary Systems AcX₄? MX₂ (Ac = Th, U; M = Ca, Sr, Ba, Eu, Ge, Sn, Pb; X = Br, I) T,x-phase diagrams of the systems ThI₄? SnI₂, ThI₄? PbI₂, ThI₄? CaI₂, and ThI₄? SrI₂ were established using thermoanalysis and x-ray methods. The only ternary compounds have a 1:1 composition. Further AcMX₆ compounds (Ac: Th, U; M: Ca, Sr, Ba, Eu, Ge, Sn, Pb; X: Br, I) were synthesized and their structures investigated. Four structure types are found depending on the temperature and the Ac/M combinations. The structures of γ-ThSnI₆ and β-ThSnI₆ were determined with single crystal methods as representatives of a whole series of isotypic compounds.     

Photopolymers for Rapid Prototyping of Soluble Mold Materials and Molding of Cellular Biomaterials

To substitute cross-linked photopolymers in rapid prototyping of mold materials and therefore extend the range of materials which can be casted, organo-soluble photopolymers were developed. Branched bisalkylacrylamides were suitable as base component for such formulations, due to their high reactivity, good mechanical properties, and excellent solubility of the formed polymers. These molding materials were used to prepare cellular biocompatible materials which could be used as bone replacement materials. Biocompatible crosslinkers based on methacrylates from hydrolyzed gelatine or lactic acid ethyleneglycol blockcopolymers and commercially available reactive diluents are the base components of such a formulation. Biocompatibility was investigated by osteoblast-like cells. Cellular biocompatible parts were obtained by thermal polymerization in soluble mould materials prepared by 3D-photoshaping.