Assembly of the water-oxidizing complex in photosystem II

The efficient incorporation and assembly of calcium, chloride and manganese followed by photoactivation of the water-oxidizing complex (WOC) is a prerequisite for the unique water-splitting activity of photosystem II. This minireview summarizes the recent results on incorporation and storage of the inorganic cofactors, photoactivation of the WOC and assembly of the protein environment at the donor site of PSII in cyanobacteria with a special focus on the role of the Psb27 protein.     

Transmission and trapping of cold electrons in water ice

Experiments are reported which show that currents of low energy ("cold") electrons pass unattenuated through crystalline ice at 135 K for energies between zero and 650 meV, up to the maximum studied film thickness of 430 bilayers, indicating negligible apparent trapping. By contrast, both porous amorphous ice and compact crystalline ice at 40 K show efficient electron trapping. Ice at intermediate temperatures reveals metastable trapping that decays within a few hundred seconds at 110 K. Our results are the first to demonstrate full transmission of cold electrons in high temperature water ice and the phenomenon of temperature-dependent trapping.     

Automated clustering of probe molecules from solvent mapping of protein surfaces: new algorithms applied to hot-spot mapping and structure-based drug design

Use of solvent mapping, based on multiple-copy minimization (MCM) techniques, is common in structure-based drug discovery. The minima of small-molecule probes define locations for complementary interactions within a binding pocket. Here, we present improved methods for MCM. In particular, a Jarvis-Patrick (JP) method is outlined for grouping the final locations of minimized probes into physical clusters. This algorithm has been tested through a study of protein-protein interfaces, showing the process to be robust, deterministic, and fast in the mapping of protein "hot spots." Improvements in the initial placement of probe molecules are also described. A final application to HIV-1 protease shows how our automated technique can be used to partition data too complicated to analyze by hand. These new automated methods may be easily and quickly extended to other protein systems, and our clustering methodology may be readily incorporated into other clustering packages.     

Controlled cell proliferation on an electrochemically engineered collagen scaffold

Therapies for corneal disease and injury often rely on artificial implants, but integrating cells into synthetic corneal materials remains a significant challenge. The electrochemically formed collagen-based matrix presented here is non-toxic to cells and controls the proliferation in the corneal fibroblasts seeded onto it. Histology and biomolecular studies show a behavior similar to corneal stromal cells in a native corneal environment. Not only is this result an important first step toward developing a more realistic, multi-component artificial cornea, but it also opens possibilities for using this matrix to control and contain the growth of cells in engineered tissues.     

Thermal analysis of organically modified siloxane melting gels

Hybrid melting gels were prepared by a sol–gel process, starting with a mono-substituted siloxane and a di-substituted siloxane, methyltrimethoxysilane (MTES) together with dimethyldimethoxysilane (DMDES). Five gel compositions were prepared with concentrations between 50% MTES–50% DMDES and 75% MTES–25% DMDES (in mol.%). The consolidation temperature, the treatment temperature after which the melting gel no longer softens, increased from 135 to 160 °C with a decrease in the amount of the mono-substituted siloxane. The glass transition temperature, recorded with differential scanning calorimetry, decreased from −0.3 to −56.7 °C with a decrease in the amount of the mono-substituted siloxane. When a sample was heat treated isothermally for 2 h at the consolidation temperature, the glass transition temperature increased by about 15°, indicating further crosslinking of the siloxane network.     

Selective monocationic inhibitors of neuronal nitric oxide synthase. Binding mode insights from molecular dynamics simulations

The reduction of pathophysiologic levels of nitric oxide through inhibition of neuronal nitric oxide synthase (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. We have developed a series of pyrrolidine-based nNOS inhibitors that exhibit excellent potencies and isoform selectivities (J. Am. Chem. Soc. 2010, 132, 5437). However, there are still important challenges, such as how to decrease the multiple positive charges derived from basic amino groups, which contribute to poor bioavailability, without losing potency and/or selectivity. Here we present an interdisciplinary study combining molecular docking, crystallography, molecular dynamics simulations, synthesis, and enzymology to explore potential pharmacophoric features of nNOS inhibitors and to design potent and selective monocationic nNOS inhibitors. The simulation results indicate that different hydrogen bond patterns, electrostatic interactions, hydrophobic interactions, and a water molecule bridge are key factors for stabilizing ligands and controlling ligand orientation. We find that a heteroatom in the aromatic head or linker chain of the ligand provides additional stability and blocks the substrate binding pocket. Finally, the computational insights are experimentally validated with double-headed pyridine analogues. The compounds reported here are among the most potent and selective monocationic pyrrolidine-based nNOS inhibitors reported to date, and 10 shows improved membrane permeability.     

Infrared spectroscopy of solid hydrogen sulfide and deuterium sulfide

The infrared spectra of solid hydrogen sulfide (H2S) and deuterium sulfide (D2S) were collected at very low temperatures. Vapor deposition of thin films at the lowest temperature of 10 K produced amorphous solids while deposition at 70 K yielded the crystalline phase III. Infrared interference fringe patterns produced by the films during deposition were used to determine the film thickness. Careful measurement of the integrated absorbance peaks, along with the film thickness, allowed determination of the integrated band intensities. This report represents the first complete presentation of the infrared spectra of the amorphous solids. Observations of peaks near 3.915 and 1.982 microm (ca. 2554 and 5045 cm(-1), respectively) may be helpful in the conclusive identification of solid hydrogen sulfide on the surface of Io, a moon of Jupiter.     

Thioamide pincer ligands with charge versatility

This paper reports the synthesis and characterization of three complexes, two palladium and one platinum, with 2,6-bis-thioamido-phenyl and 2,6-bis-thioamido-pyridine ligands. The ligands show internal charge versatility by losing protons from a phenyl CH (I) or from amide NH's (II and III). The complexes were also examined as Heck catalysts, and the palladacycle, I, was found to be more effective compared to the others. The crystal structures of the complexes are also reported.