Electronic Structure of an [FeFe] Hydrogenase Model Complex in Solution Revealed by X-ray Absorption Spectroscopy Using Narrow-Band Emission Detection

High-resolution X-ray absorption spectroscopy with narrow-band X-ray emission detection, supported by density functional theory calculations (XAES-DFT), was used to study a model complex, ([Fe(2)(μ-adt)(CO)(4)(PMe(3))(2)] (1, adt = S-CH(2)-(NCH(2)Ph)-CH(2)-S), of the [FeFe] hydrogenase active site. For 1 in powder material (1(powder)), in MeCN solution (1'), and in its three protonated states (1H, 1Hy, 1HHy; H denotes protonation at the adt-N and Hy protonation of the Fe-Fe bond to form a bridging metal hydride), relations between the molecular structures and the electronic configurations were determined. EXAFS analysis and DFT geometry optimization suggested prevailing rotational isomers in MeCN, which were similar to the crystal structure or exhibited rotation of the (CO) ligands at Fe1 (1(CO), 1Hy(CO)) and in addition of the phenyl ring (1H(CO,Ph), 1HHy(CO,Ph)), leading to an elongated solvent-exposed Fe-Fe bond. Isomer formation, adt-N protonation, and hydride binding caused spectral changes of core-to-valence (pre-edge of the Fe K-shell absorption) and of valence-to-core (K?(2,5) emission) electronic transitions, and of Kα RIXS data, which were quantitatively reproduced by DFT. The study reveals (1) the composition of molecular orbitals, for example, with dominant Fe-d character, showing variations in symmetry and apparent oxidation state at the two Fe ions and a drop in MO energies by ～1 eV upon each protonation step, (2) the HOMO-LUMO energy gaps, of ～2.3 eV for 1(powder) and ～2.0 eV for 1', and (3) the splitting between iron d(z(2)) and d(x(2)-y(2)) levels of ～0.5 eV for the nonhydride and ～0.9 eV for the hydride states. Good correlations of reduction potentials to LUMO energies and oxidation potentials to HOMO energies were obtained. Two routes of facilitated bridging hydride binding thereby are suggested, involving ligand rotation at Fe1 for 1Hy(CO) or adt-N protonation for 1HHy(CO,Ph). XAES-DFT thus enables verification of the effects of ligand substitutions in solution for guided improvement of [FeFe] catalysts.     

An alternative approach to well-posedness of a class of differential inclusions in Hilbert spaces

We show the well-posedness of initial value problems for differential inclusions of a certain type using abstract perturbation results for maximal monotone operators in Hilbert spaces. For this purpose the time derivative is established in an exponentially weighted _L2$L_2$ space. The problem of well-posedness then reduces to show that the sum of two maximal monotone operators in time and space is again maximal monotone. The theory is exemplified by three inclusions describing phenomena in mathematical physics involving hysteresis.     

Metric Expansion from Microscopic Dynamics in an Inhomogeneous Universe

Theories with ingredients like the Higgs mechanism, gravitons, and inflatonfields rejuvenate the idea that relativistic kinematics is dynamicallyemergent. Eternal inflation treats the Hubble constant H as depending onlocation. Microscopic dynamics implies that H is over much smaller lengthsthan pocket universes to be understood as a local space reproduction rate.We illustrate this via discussing that even exponential inflation inTeV-gravity is slow on the relevant time scale. In our on small scalesinhomogeneous cosmos, a reproduction rate H depends on position. We therefore discuss Einstein-Strauss vacuoles and a Lindquist-Wheeler like lattice to connect the local rate properly with the scaling of an expanding cosmos. Consistency allows H to locally depend on Weyl curvature similar to vacuum polarization. We derive a proportionality constant known from Kepler's third law and discuss the implications for the finiteness of the cosmological constant.     

Comparative Analysis of the Antitumor Activity of Cis- and Trans-Resveratrol in Human Cancer Cells with Different p53 Status

Resveratrol, a natural plant phytoalexin, is produced in response to fungal infection or− UV irradiation. It exists as an isomeric pair with cis- and trans-conformation. Whereas multiple physiological effects of the trans-form, including a pronounced anti-tumoral activity, are nowadays elucidated, much less knowledge exists concerning the cis-isomer. In our work, we analyzed the antiproliferative and cytotoxic properties of cis-resveratrol in four different human tumor entities in direct comparison to trans-resveratrol. We used human cell lines as tumor models for hepatocellular carcinoma (HCC; HepG2, Hep3B), colon carcinoma (HCT-116, HCT-116/p53^(−/−)), pancreatic carcinoma (Capan-2, MiaPaCa-2), and renal cell carcinoma (A498, SN12C). Increased cytotoxicity in all investigated tumor cells was observed for the trans-isomer. To verify possible effects of the tumor suppressor p53 on resveratrol-induced cell death, we used wild type and p53-deleted or -mutated cell lines for every tested tumor entity. Applying viability and cytotoxicity assays, we demonstrated a differential, dose-dependent sensitivity towards cis- or trans-resveratrol among the respective tumor types.     

A pH-Induced Reversible Conformational Switch Able to Control the Photocurrent Efficiency in a Peptide Supramolecular System

External stimuli are potent tools that Nature uses to control protein function and activity. For instance, during viral entry and exit, pH variations are known to trigger large protein conformational changes. In Nature, also the electron transfer (ET) properties of ET proteins are influenced by pH-induced conformational changes. In this work, a pH-controlled, reversible 3₁₀-helix to α-helix conversion (from acidic to highly basic pH values and vice versa) of a peptide supramolecular system built on a gold surface is described. The effect of pH on the ability of the peptide SAM to generate a photocurrent was investigated, with particular focus on the effect of the pH-induced conformational change on photocurrent efficiency. The films were characterized by electrochemical and spectroscopic techniques, and were found to be very stable over time, also in contact with a solution. They were also able to generate current under illumination, with an efficiency that is the highest recorded so far with biomolecular systems.     

Electrochemical texturing of Al-doped ZnO thin films for photovoltaic applications

The processes during chemical and electrochemical etching of Al-doped ZnO are investigated utilizing a scanning flow cell setup with online detection of dissolved Zn ions. The rate of chemical dissolution was found to be a linear function of buffer and proton concentration in near neutral pH solutions according to a transport limited reaction. In contrast, electrochemical etching is limited by the kinetics of the reaction and increases linearly with the imposed current density. Due to this fundamental difference, the dissolution of Zn can be either uniform over the whole surface or highly localized at active sites like grain boundaries. A combined approach of chemical etching and the well-controllable galvanostatic dissolution thus allows a fine adjustment of the ZnO:Al surface texture for applications in silicon thin film photovoltaic cells in order to improve their overall energy conversion efficiency.     

Psoromic acid is a selective and covalent Rab-prenylation inhibitor targeting autoinhibited RabGGTase

Post-translational attachment of geranylgeranyl isoprenoids to Rab GTPases, the key organizers of intracellular vesicular transport, is essential for their function. Rab geranylgeranyl transferase (RabGGTase) is responsible for prenylation of Rab proteins. Recently, RabGGTase inhibitors have been proposed to be potential therapeutics for treatment of cancer and osteoporosis. However, the development of RabGGTase selective inhibitors is complicated by its structural and functional similarity to other protein prenyltransferases. Herein we report identification of the natural product psoromic acid (PA) that potently and selectively inhibits RabGGTase with an IC(50) of 1.3 μM. Structure-activity relationship analysis suggested a minimal structure involving the depsidone core with a 3-hydroxyl and 4-aldehyde motif for binding to RabGGTase. Analysis of the crystal structure of the RabGGTase:PA complex revealed that PA forms largely hydrophobic interactions with the isoprenoid binding site of RabGGTase and that it attaches covalently to the N-terminus of the α subunit. We found that in contrast to other protein prenyltransferases, RabGGTase is autoinhibited through N-terminal (α)His2 coordination with the catalytic zinc ion. Mutation of (α)His dramatically enhances the reaction rate, indicating that the activity of RabGGTase is likely regulated in vivo. The covalent binding of PA to the N-terminus of the RabGGTase α subunit seems to potentiate its interaction with the active site and explains the selectivity of PA for RabGGTase. Therefore, psoromic acid provides a new starting point for the development of selective RabGGTase inhibitors.     

Cobalt and Iron Stabilized Ketyl,Ketiminyl and Aldiminyl Radical Anions

Carbonyl and iminyl based radical anions are reactive intermediates in a variety of transformations in organic synthesis. Herein, the isolation of ketyl, and more importantly unprecedented ketiminyl and aldiminyl radical anions coordinated to cobalt and iron complexes is presented. Insights into the electronic structure of these unusual metal bound radical anions is provided by X-Ray diffraction analysis, NMR, IR, UV/Vis and Mössbauer spectroscopy, solid and solution state magnetometry, as well as a by a detailed computational analysis. The metal bound radical anions are very reactive and facilitate the activation of intra- and intermolecular C−H bonds.