Surface-template assembly of two-dimensional metal-organic coordination networks

The self-assembly of iron-coordinated two-dimensional metal-organic networks on a Cu(100) surface has been investigated by scanning tunneling microscopy under ultra-high-vacuum conditions. We applied three rodlike polybenzene dicarboxylic acid molecules with different backbone lengths as organic linkers. The three linker molecules form topologically identical rectangular networks with Fe, all comprising iron pairs as the network nodes. Whereas the length of the linker molecules defines the dimension of the networks, the substrate also significantly influences the structural details, e.g., network orientation with respect to the substrate, geometric shape of the network cavities, Fe-carboxylate coordination configuration, and iron-iron distance.     

On the morphology and stability of Au nanoparticles on TiO2(110) prepared from micelle-stabilized precursors

The morphology and stability of well-ordered, nanostructured Au/TiO2(110) surfaces, prepared by deposition of Au loaded micelles on TiO2(110) substrates and subsequent oxidative removal of the polymer shell in an oxygen plasma, was investigated by noncontact AFM, SEM and XPS. The resulting arrays of Au nanoparticles (particle sizes 1-5 nm) form a nearly hexagonal pattern with well-defined interparticle distances and a narrow particle size distribution. Particle size and particle separation can be controlled independently by varying the Au loading and the block-copolymers in the micelle shell. The oxygen plasma treatment does not affect the size and distance of the Au nanoparticles; the latter are fully metallic after subsequent UHV annealing (400 degrees C). The particles are stable under typical CO oxidation reaction conditions, up to at least 200 degrees C, making these surfaces ideally suited as defined model systems for catalytic studies. Significant changes in the height distributions of the Au nanoparticles are found upon 400 degrees C annealing in O2. For adlayers with small interparticle distances, this leads to a bimodal particle size distribution, which together with the preservation of the lateral order points to Ostwald ripening.     

p53--a natural cancer killer: structural insights and therapeutic concepts

Every single day, the DNA of each cell in the human body is mutated thousands of times, even in absence of oncogenes or extreme radiation. Many of these mutations could lead to cancer and, finally, death. To fight this, multicellular organisms have evolved an efficient control system with the tumor-suppressor protein p53 as the central element. An intact p53 network ensures that DNA damage is detected early on. The importance of p53 for preventing cancer is highlighted by the fact that p53 is inactivated in more than 50 % of all human tumors. Thus, for good reason, p53 is one of the most intensively studied proteins. Despite the great effort that has been made to characterize this protein, the complex function and the structural properties of p53 are still only partially known. This review highlights basic concepts and recent progress in understanding the structure and regulation of p53, focusing on emerging new mechanistic and therapeutic concepts.     

N-K electron energy-loss near-edge structures for TiN/VN layers: an ab initio and experimental study

We study N-K-edge electron energy-loss near-edge structures for well-defined TiN/VN bilayers grown on a MgO(100) substrate by both calculations and experiments. The structural relaxations and the electronic structure of TiN/VN multilayers are calculated using the Vienna Ab Initio Simulation Package computer code, which uses density functional theory to describe the electronic interaction. The effects of the core hole created in the excitation process are included in the calculations. For VN, off-stoichiometric effects due to nitrogen vacancies are modelled. The partial density of states (PDOS) for the N-K edge of atoms in the vicinity of the TiN/MgO interface revealed that two new peaks appear between 7 and 9 eV instead of a broad shoulder typical for the bulk. For the VN/TiN interface, the PDOS is modified only slightly, owing to similar bonding on both sides of the interface, and is thus very similar to the respective bulk spectra. An experimental spectrum taken at the VN/TiN interface is, however, well described by an average of the simulated spectra for VN and TiN bulk (interface). Such a finding is characteristic of an intermixed interface.      

Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors

Receptor tyrosine kinases (RTKs) are key regulators of cellular functions in metazoans. In vertebrates, RTKs are mostly activated by polypeptides but are not naturally sensitive to amino acids or light. Taking inspiration from Venus kinase receptors (VKRs), an atypical family of RTKs found in nature, we have transformed the human insulin (hIR) and hepatocyte growth factor receptor (hMET) into glutamate receptors by replacing their extracellular binding domains with the ligand‐binding domain of metabotropic glutamate receptor type 2 (mGluR2). We then imparted light sensitivity through covalent attachment of a synthetic glutamate‐based photoswitch via a self‐labelling SNAP tag. By employing a Xenopus laevis oocyte kinase activity assay, we demonstrate how these chimeric RTKs, termed light‐controlled human insulin receptor (LihIR) and light‐controlled human MET receptor (LihMET), can be used to exert optical control over the insulin or MET signaling pathways. Our results outline a potentially general strategy to convert RTKs into photoreceptors.     

A Multi‐action and Multi‐target RuII–PtIV Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

Pt^II complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt^IV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru^II polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt^IV–Ru^II conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt^IV centre is reduced to Pt^II and the axial ligands including the Ru^II complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi‐target and multi‐action effect with (photo‐)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.     

The Critical Role of Reductive Steps in the Nickel‐Catalyzed Hydrogenolysis and Hydrolysis of Aryl Ether C−O Bonds

The hydrogenolysis of the aromatic C?O bond in aryl ethers catalyzed by Ni was studied in decalin and water. Observations of a significant kinetic isotope effect (k_H/k_D=5.7) for the reactions of diphenyl ether under H₂ and D₂ atmosphere and a positive dependence of the rate on H₂ chemical potential in decalin indicate that addition of H to the aromatic ring is involved in the rate‐limiting step. All kinetic evidence points to the fact that H addition occurs concerted with C?O bond scission. DFT calculations also suggest a route consistent with these observations involving hydrogen atom addition to the ipso position of the phenyl ring concerted with C?O scission. Hydrogenolysis initiated by H addition in water is more selective (ca. 75 %) than reactions in decalin (ca. 30 %).     

Model‐Based Nanoengineered Pharmacokinetics of Iron‐Doped Copper Oxide for Nanomedical Applications

The progress in nanomedicine (NM) using nanoparticles (NPs) is mainly based on drug carriers for the delivery of classical chemotherapeutics. As low NM delivery rates limit therapeutic efficacy, an entirely different approach was investigated. A homologous series of engineered CuO NPs was designed for dual purposes (carrier and drug) with a direct chemical composition–biological functionality relationship. Model‐based dissolution kinetics of CuO NPs in the cellular interior at post‐exposure conditions were controlled through Fe‐doping for intra/extra cellular Cu²⁺ and biological outcome. Through controlled ion release and reactions taking place in the cellular interior, tumors could be treated selectively, in vitro and in vivo. Locally administered NPs enabled tumor cells apoptosis and stimulated systemic anti‐cancer immune responses. We clearly show therapeutic effects without tumor cells relapse post‐treatment with 6 % Fe‐doped CuO NPs combined with myeloid‐derived suppressor cell silencing.