Inverse Polyamidoamine (i-PAMAM) Dendrimer Antimicrobials

Here we redesigned the branches of polyamidoamine (PAMAM) dendrimers by moving the amide carbonyl group on the other side of the amide nitrogen atom, transforming the β-alaninyl-amidoethylamine branch, which easily undergoes retro-Michael reactions and renders PAMAMs intrinsically unstable, into a more stable glycyl-amidopropylamine branch. The resulting inverse PAMAM (i-PAMAM) dendrimers have the same carbon framework as PAMAMs and only differ by the position of the carbonyl group. In contrast to PAMAMs which are prepared in solution and are difficult to purify, we synthesize i-PAMAMs using high-temperature solid-phase peptide synthesis by iterative coupling and deprotection of the commercially available N,N-bis(N′-Fmoc-3-aminopropyl)glycine and purify them preparative reverse phase HPLC. Our i-PAMAM dendrimers show no detectable degradation over time. We demonstrate this new class of dendrimers with the synthesis of antimicrobial dendrimers with potent yet non-membrane disruptive activities against both Gram-negative and Gram-positive bacteria.     

Compound I in heme thiolate enzymes: a comparative QM/MM study

This study directly compares the active species of heme enzymes, so-called Compound I (Cpd I), across the heme-thiolate enzyme family. Thus, sixty-four different Cpd I structures are calculated by hybrid quantum mechanical/molecular mechanical (QM/MM) methods using four different cysteine-ligated heme enzymes (P450(cam), the mutant P450(cam)-L358P, CPO and NOS) with varying QM region sizes in two multiplicities each. The overall result is that these Cpd I species are similar to each other with regard to many characteristic features. Hence, using the more stable CPO Cpd I as a model for P450 Cpd I in experiments should be a reasonable approach. However, systematic differences were also observed, and it is shown that NOS stands out in most comparisons. By analyzing the electrical field generated by the enzyme on the QM region, one can see that (a) the protein exerts a large influence and modifies all the Cpd I species compared with the gas-phase situation and (b) in NOS this field is approximately planar to the heme plane, whereas it is approximately perpendicular in the other enzymes, explaining the deviating results on NOS. The calculations on the P450(cam) mutant L358P show that the effects of removing the hydrogen bond between the heme sulfur and L358 are small at the Cpd I stage. Finally, Mossbauer parameters are calculated for the different Cpd I species, enabling future comparisons with experiments. These results are discussed in the broader context of recent findings of Cpd I species that exhibit large variations in the electronic structure due to the presence of the substrate.     

On the shape of interlayer vortices in the Lawrence-Doniach model

We consider the Lawrence-Doniach model for layered superconductors, in which stacks of parallel superconducting planes are coupled via the Josephson effect. To model experiments in which the superconductor is placed in an external magnetic field oriented parallel to the superconducting planes, we study the structure of isolated vortices for a doubly periodic problem. We consider a singular limit which simulates certain experimental regimes in which isolated vortices have been observed, corresponding to letting the interlayer spacing of the superconducting planes tend to zero and the Ginzburg-Landau parameter simultaneously, but at a fixed relative rate.

     

Synthesis of hybrid gold-gold sulfide colloidal particles

The nucleation and growth mechanism of nanometer size gold onto gold sulfide colloidal particles by irradiation-induced reduction is reported. The process is characterized by ultraviolet-visible spectroscopy, electronic diffraction, and high-resolution transmission electron microscopy, allowing for observation of several key intermediates and characteristics of the growth mechanism. The formation mechanism of gold on the surface of the gold sulfide particles is shown to depend strongly on the deposition rate. At low dose rate, gold nucleates preferentially onto specific gold-rich Au2S facets {110}, resulting in epitaxial growth. The gold crystal lattice plastically deforms near the interface to accommodate a substantial lattice mismatch. Upon increasing gold precursor concentration, this low dose rate results in growth of elongated gold island on the gold sulfide surface. At a high dose rate, several randomly oriented gold particles are simultaneously produced on gold sulfide, resulting in a layered structure. The absorption spectra of these particles show a dominant surface plasmon band, whose peak wavelength shifts markedly to the red as layered structure is formed.     

Mangrove trees growing in a very saline condition but not using seawater

Mangrove trees, which develop along tropical coasts, are known to use saline water uptake. In French Guiana, the high salinity condition is the result of seawater evaporation on mud banks formed from the Amazon sediment flumes. In the back mangrove a few kilometres inland, groundwater, soil water and the xylem sap uptake in the trees remain highly salty, and only very tolerant plants like Avicennia germinans can flourish, whereas the less salt-tolerant Rhizophora mangle is more difficult to find. Curiously, the same Avicennia trees propagate on the seafront. However, stable isotope ratio mass spectrometry (IRMS) measurements and ion analysis (high-performance liquid chromatography (HPLC) and inductively coupled plasma atomic emission (ICP-AES) spectroscopy reveal that the origin of the water in the back mangrove is not seawater. It is freshwater percolating into the sand bars from the inland marshes and rainwater during the wet season that redissolves a marine evaporite and gives a saline groundwater. The absence of barren saltine areas ('tanne') in French Guiana could be explained by this freshwater inflow, the aquifer being no longer linked with the ocean. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Quantum mechanical/molecular mechanical study of mechanisms of heme degradation by the enzyme heme oxygenase: the strategic function of the water cluster

Heme degradation by heme oxygenase (HO) enzymes is important in maintaining iron homeostasis and prevention of oxidative stress, etc. In response to mechanistic uncertainties, we performed quantum mechanical/molecular mechanical investigations of the heme hydroxylation by HO, in the native route and with the oxygen surrogate donor H2O2. It is demonstrated that H2O2 cannot be deprotonated to yield Fe(III)OOH, and hence the surrogate reaction starts from the FeHOOH complex. The calculations show that, when starting from either Fe(III)OOH or Fe(III)HOOH, the fully concerted mechanism involving O-O bond breakage and O-C(meso) bond formation is highly disfavored. The low-energy mechanism involves a nonsynchronous, effectively concerted pathway, in which the active species undergoes first O-O bond homolysis followed by a barrier-free (small with Fe(III)HOOH) hydroxyl radical attack on the meso position of the porphyrin. During the reaction of Fe(III)HOOH, formation of the Por+*FeIV=O species, compound I, competes with heme hydroxylation, thereby reducing the efficiency of the surrogate route. All these conclusions are in accord with experimental findings (Chu, G. C.; Katakura, K.; Zhang, X.; Yoshida, T.; Ikeda-Saito, M. J. Biol. Chem. 1999, 274, 21319). The study highlights the role of the water cluster in the distal pocket in creating "function" for the enzyme; this cluster affects the O-O cleavage and the O-Cmeso formation, but more so it is responsible for the orientation of the hydroxyl radical and for the observed alpha-meso regioselectivity of hydroxylation (Ortiz de Montellano, P. R. Acc. Chem. Res. 1998, 31, 543). Differences/similarities with P450 and HRP are discussed.     

Interaction between water-soluble peptidic CdSe/ZnS nanocrystals and membranes: formation of hybrid vesicles and condensed lamellar phases

Due to their tunable optical properties and their well-defined nanometric size, core/shell nanocrystals (quantum dots, QDs) are extensively used for the design of biomarkers as well as for the preparation of nanostructured hybrid materials. It is thus of great interest to understand their interaction with soft lipidic membranes. Here we present the synthesis of water-soluble peptide CdSe/ZnS QDs and their interaction with the fluid lipidic membrane of vesicles. The use of short peptides results in the formation of small QDs presenting both high fluorescence quantum yield and high colloidal stability as well as a mean hydrodynamical diameter of 10 nm. Their interaction with oppositely charged vesicles of various surface charge and size results in the formation of hybrid giant or large unilamellar vesicles covered with a densely packed layer of QDs without any vesicle rupture, as demonstrated by fluorescence resonance energy transfer experiments, zetametry, and optical microscopy. The adhesion of nanocrystals onto the vesicle membrane appears to be sterically limited and induces the reversion of the surface charge of the vesicles. Therefore, their interaction with small unilamellar vesicles induces the formation of a well-defined lamellar hybrid condensed phase in which the QDs are densely packed in the plane of the layers, as shown by freeze-fracture electron microscopy and small-angle X-ray scattering. In this structure, strong undulations of the bilayer maximize the electrostatic interaction between the QDs and the bilayers, as previously observed in the case of DNA polyelectrolytes interacting with small vesicles.     

Structure and magnetic properties of oxychalcogenides A2F2Fe2OQ2 (A = Sr, Ba; Q = S, Se) with Fe2O square planar layers representing an antiferromagnetic checkerboard spin lattice

The oxychalcogenides A2F2Fe2OQ2 (A = Sr, Ba; Q = S, Se), which contain Fe2O square planar layers of the anti-CuO2 type, were predicted using a modular assembly of layered secondary building units and subsequently synthesized. The physical properties of these compounds were characterized using magnetic susceptibility, electrical resistivity, specific heat, (57)Fe Mossbauer, and powder neutron diffraction measurements and also by estimating their exchange interactions on the basis of first-principles density functional theory electronic structure calculations. These compounds are magnetic semiconductors that undergo a long-range antiferromagnetic ordering below 83.6-106.2 K, and their magnetic properties are well-described by a two-dimensional Ising model. The dominant antiferromagnetic spin exchange interaction between S = 2 Fe(2+) ions occurs through corner-sharing Fe-O-Fe bridges. Moreover, the calculated spin exchange interactions show that the A2F2Fe2OQ2 (A = Sr, Ba; Q = S, Se) compounds represent a rare example of a frustrated antiferromagnetic checkerboard lattice.     

alpha-glucosidase inhibitors from Garcinia brevipedicellata (Clusiaceae)

In our continuous search for alpha-glucosidase inhibitors from plants, four new depsidones named brevipsidones A-D (1-4) were isolated from stem bark of Garcinia brevipedicellata together with known damnacanthal, scopoletin and a mixture of stigmasterol and beta-sitosterol. Structural elucidations were made by spectroscopic analyses including 2D-NMR data.