Anion receptors containing -NH binding sites: hydrogen-bond formation or neat proton transfer?

When the amide-containing receptor 1(+) is in a solution of dimethyl sulfoxide (DMSO) in the presence of basic anions (CH(3)COO(-), F(-), H(2)PO(4) (-)), it undergoes deprotonation of the -NH fragment to give the corresponding zwitterion, which can be isolated as a crystalline solid. In the presence of less basic anions (Cl(-), Br(-), NO(3) (-)), 1(+) establishes true hydrogen-bond interactions of decreasing intensity. The less acidic receptor 2(+) undergoes neat proton transfer with only the more basic anions CH(3)COO(-) and F(-), and establishes hydrogen-bond interactions with H(2)PO(4) (-). An empirical criterion for discerning neutralisation and hydrogen bonding, based on UV/Vis and (1)H NMR spectra, is proposed.     

Palladium: a future key player in the nanomedical field?

Metal nanostructures offer invaluable possibilities for targeted drug delivery, detection/diagnosis and imaging. Whereas iron, gold, silver and platinum nanoarchitectures have largely dominated this field to date, several hurdles impede the widespread application of those nanopharmaceuticals in a clinical context. Therefore, technologies based on alternative metals are now being evaluated for their potential in medical applications. Palladium nanostructures are characterized by remarkable catalytic and optical properties. However, until recently, very few studies have taken advantage of these unique characteristics for applications in the biomedical field. Very recently, palladium nanostructures have been reported as prodrug activator, as photothermal agents and for anti-cancer/anti-microbial therapy. With only a handful of reports available, the pharmaceutical applications of palladium nanostructures reviewed here are in their infancy. Yet their interesting performance and toxicity profiles may qualify them as future key players in the nanomedical field.     

416 - Surface and/or donnan potentials at the thylakoid membrane?: Part III. Experimental results for a 1 : 1 electrolyte

The light-induced change of the transmembrane potential of spinach thylakoids is measured via the electrochromic absorption change, which is corrected for additionally occurring light-scattering changes. The potential is negligible for KCl concentrations > 5 × 10⁻² M, which suggests the interpretation as a generalized Donnan potential with constant internal volume. Accordingly, the variation of the dark volume with KCl concentration, which does occur and is measured by radioactive labelling of the water, cannot be described by an osmotic equilibrium with freely variable volume.     

Recognition of mandelate stereoisomers by chiral porphyrin hosts: prediction of stereopreference in guest binding a priori using a simple binding model?

Rigid porphyrin hosts that mimic the spatial arrangement of mandelate recognition motifs lead to stereoselective receptors and illustrate how subtle structural differences in host design have significant impact on guest recognition. The porphyrin hosts are obtained with minimal synthetic effort from readily available chiral amine precursors and are modular in design. The chiral recognition properties of the porphyrin-based hosts with chiral carboxylate-containing guests and chiral amines are described. UV/vis and ¹H NMR spectroscopic results indicate some of these porphyrin hosts undergo an induced fit conformational change upon guest binding.     

Julia–Kocienski olefination: a key reaction for the synthesis of macrolides

The unification of carbonyl compounds and heteroaryl sulfones provides one of the best methods for the construction of C–C double bond for synthetic chemists in designing synthetic routes to natural and non-natural products. For the C–C double bond formation, olefination, particularly the Julia–Kocienski olefination (JK-olefination) has emerged as a powerful key reaction in the synthesis of natural products that contain macrocycles. Molecules of interest include macrolides, whose biological importance, lack of natural resources, and interesting structure placed a challenge among the scientific community for their total synthesis. Thus, for systematic documentation we have summarized the synthetic approaches toward several important macrolides highlighting the Julia–Kocienski olefination as one of the key steps. This review is intended to show the utility of the Julia–Kocienski olefination in the synthesis of biologically important macrocyclic natural products.     

Flavonoids: A Myth or a Reality for Cancer Therapy?

Nutraceuticals are biologically active molecules present in foods; they can have beneficial effects on health, but they are not available in large enough quantities to perform this function. Plant metabolites, such as polyphenols, are widely diffused in the plant kingdom, where they play fundamental roles in plant development and interactions with the environment. Among these, flavonoids are of particular interest as they have significant effects on human health. In vitro and/or in vivo studies described flavonoids as essential nutrients for preventing several diseases. They display broad and promising bioactivities to fight cancer, inflammation, bacterial infections, as well as to reduce the severity of neurodegenerative and cardiovascular diseases or diabetes. Therefore, it is not surprising that interest in flavonoids has sharply increased in recent years. More than 23,000 scientific publications on flavonoids have described the potential anticancer activity of these natural molecules in the last decade. Studies, in vitro and in vivo, show that flavonoids exhibit anticancer properties, and many epidemiological studies confirm that dietary intake of flavonoids leads to a reduced risk of cancer. This review provides a glimpse of the mechanisms of action of flavonoids on cancer cells.     

Do amorphous troglitazones prepared from two diastereomer-pairs have the same molecular mobility and crystallization rate at the surface?

The surface of amorphous compounds crystallizes faster compared to the bulk. This suggests that molecules at the surface have high molecular mobility. Crystallization behavior is affected by various factors including molecular weight and glass transition temperature (T(g)). In this study, we focus on troglitazone which is composed of diastereomers, RR/SS and RS/SR, as model compound, because each diastereomer has the same molecular weight and similar chemical structure. Troglitazone is isolated into each diastereomer, and both amorphous prepared from RR/SS and RS/SR showed similar T(g) (around 60°C). The surface relaxation of each amorphous troglitazone prepared from two diastereomers, RR/SS and RS/SR, was determined to compare surface molecular mobility, using inverse gas chromatography under dry conditions. As a result, amorphous prepared from RS/SR, showed the shorter surface relaxation time at 40°C (temperature below T(g)), which means it has higher molecular mobility than that from RR/SS at the surface although both have the same molecular weight and similar T(g). Microscopy analysis was conducted to observe the crstallization behavior at the surface of amorphous troglitazone in conditions of high temperature and humidity. Micrographs showed that crystallization area at the surface of amorphous prepared from RS/SR, which showed the shorter surface relaxation time, increased faster than that of the amorphous prepared from RR/SS. Although the reason for the difference in the surface relaxation time of each amorphous troglitazone could not be determined, factors such as the difference of configuration might affect the difference.     

415 - Surface and/or Donnan potentials at the thylakoid membrane?: Part II. Calculation of light-induced surface potential changes and corresponding ion movement for a 1 : 1 electrolyte

The surface potential at the inner side of the thylakoid membrane in the dark and in the light state is calculated using the simple Gouy-Chapman theory, together with modifications to allow for proton binding to the surface. The corresponding transmembrane potential change and the ion transport, necessary for ion redistribution in the diffuse double layer, are formulated. the steady-state generalized Donnan potential is shown to be negligible. Finally, the surface potential representation is compared with the Donnan potential representation, given in the preceding paper. On the basis of the formula derived, measurements are discussed which will help to decide between the different concepts.     

A simple protocol for the synthesis of triazole-linked cyclic glycopeptidomimetics: a sequential Ugi-MCR and azide–alkyne cycloaddition approach

Sequential combination of Ugi-MCR and click chemistry has been employed for the synthesis of triazole linked cyclic glycopeptidomimetics. The protocol employs Poc-amino alkyl isonitriles, sugar-1-amines, azido acids, and simple aldehydes as precursors. The dual nature of the propargyloxycarbonyl (Poc) group was explored for amine protection as well as cycloaddition with an azide. All the cyclic glycopeptidomimetics are isolated and characterized.     

Asthma and Human Excellence: A Coincidence or a Correlation?

Superior intelligence, creative genius, extraordinary personality, and/or social prominence have been associated with asthma often enough to raise the question of a nonrandom concurrence. With no intent to prove any developmental correlation this article presents such “case reports” (more biographical than biological) for two main reasons: to document the experience of asthma in the life of outstanding persons and to make everyone better acquainted-using asthma as an “excuse”-with the work and the times of some unique human beings.     

A predictive, simple and rapid method for thermodynamic study on the binding of copper ion with Alzheimer''s amyloid β peptide

The interaction of CuC12 to the first 16 residues of the Alzbeimer's amyliod β peptide, Aβ(1-16) was studied by isothermal titration calorimetry at pH 7.2 and 37 ℃ in aqueous solution.     

Performance of HADDOCK and a simple contact-based protein–ligand binding affinity predictor in the D3R Grand Challenge 2

We present the performance of HADDOCK, our information-driven docking software, in the second edition of the D3R Grand Challenge. In this blind experiment, participants were requested to predict the structures and binding affinities of complexes between the Farnesoid X nuclear receptor and 102 different ligands. The models obtained in Stage1 with HADDOCK and ligand-specific protocol show an average ligand RMSD of 5.1 Å from the crystal structure. Only 6/35 targets were within 2.5 Å RMSD from the reference, which prompted us to investigate the limiting factors and revise our protocol for Stage2. The choice of the receptor conformation appeared to have the strongest influence on the results. Our Stage2 models were of higher quality (13 out of 35 were within 2.5 Å), with an average RMSD of 4.1 Å. The docking protocol was applied to all 102 ligands to generate poses for binding affinity prediction. We developed a modified version of our contact-based binding affinity predictor PRODIGY, using the number of interatomic contacts classified by their type and the intermolecular electrostatic energy. This simple structure-based binding affinity predictor shows a Kendall’s Tau correlation of 0.37 in ranking the ligands (7th best out of 77 methods, 5th/25 groups). Those results were obtained from the average prediction over the top10 poses, irrespective of their similarity/correctness, underscoring the robustness of our simple predictor. This results in an enrichment factor of 2.5 compared to a random predictor for ranking ligands within the top 25%, making it a promising approach to identify lead compounds in virtual screening.     

Two-dye and one- or two-quencher DNA probes for real-time PCR assay: synthesis and comparison with a TaqMan? probe

A typical TaqMan? real-time PCR probe contains a 5'-fluorescent dye and a 3'-quencher. In the course of the amplification, the probe is degraded starting from the 5'-end, thus releasing fluorescent dye. Some fluorophores (including fluorescein) are known to be prone to self-quenching when located near each other. This work is aimed at studying dye-dye and dye-quencher interactions in multiply modified DNA probes. Twenty-one fluorogenic probes containing one and two fluoresceins (FAM), or a FAM-JOE pair, and one or two BHQ1 quenchers were synthesized using non-nucleoside reagents and "click chemistry" post-modification on solid phase and in solution. The probes were tested in real-time PCR using an ~300-bp-long natural DNA fragment as a template. The structural prerequisites for lowering the probe background fluorescence and increasing the end-plateau fluorescence intensity were evaluated and discussed.     

Dephasing time in solids and homogeneous optical linewidth: are the mechanisms of the electron-phonon coupling the same?

The differences between theoretical formulas for the reciprocal dephasing time T₂⁻¹ and the homogeneous optical linewidth γ are discussed. Both are due to the same mechanism (quadratic electron-phonon coupling), but it is treated more approximately in the formula for T₂⁻¹.     

A new reductimetric reagent: ironII in a strong phosphoric acid medium—III: Titration of vanadiumIV or vanadiumV with ironII at room temperature: determination of chromiumVI and vanadiumV in the same solution

The formal redox potential of the V^IV/V^III couple has been determined in a medium of varying phosphoric acid concentration. From these results and those previously reported for the Fe^III/Fe^II couple, the formal redox potential of the V^IV/V^III couple is higher than that of the Fe^III/Fe^II couple for a concentration of phosphoric acid above 4-OM, the difference between the formal redox potentials increasing with increasing concentration of phosphoric acid. At a concentration of 10·5M phosphoric acid the V^IV/V^III couple has a potential which is about 0·27 V higher than that of the Fe^III/Fe^II couple, so that iron^II then rapidly reduces vanadium^IV to vanadium^III even at room temperature. Using this reaction a titrimetric procedure has been developed for determination of vanadium^IV either with a potentiometric end-point or with a visual end-point using methylene blue or thionine as redox indicators. Titrations using these indicators must be carried out in an inert atmosphere. The new reagent is more advantageous than titanium^III or chromium^II which require special storage conditions. Moreover, iron^III and tungsten^VI do not interfere with the use of this reagent as they do with titanium^III or chromium^II. Further, the new reagent enables the determination of chromium^VI and vanadium^V in a single solution to be carried out with a potentiometric end-point. The first break in the potential curve corresponds to the reduction of chromium^VI to chromium^III and of vanadium^V to vanadium^IV, and the second break corresponds to the further reduction of vanadium^IV' to vanadium^III. Iron^III, manganese^II, cobalt^II and tungsten^VI do not interfere. This procedure is likely to be of considerable value in the analysis of special steels.     

Efficient synthesis of the κ-opioid receptor agonist CJ-15,161: four stereospecific inversions at a single aziridinium stereogenic center

An efficient four-step sequence has been developed for the synthesis of the κ-opioid receptor agonist CJ-15,161. The process features four consecutive regioselective and stereospecific inversions at a single aziridinium stereogenic center, which leads to overall retention of stereochemistry, in a single operation. The chemistry is straightforward, practical and amenable to large-scale synthesis.     

Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids

The enantiospecific synthesis of unnatural unsaturated and saturated α-amino acids based on a Wittig type reaction is described. The versatile synthetic intermediates, l-glutamic and l-aspartic acid semialdehydes, are obtained from the corresponding N,N-di-Boc-diesters, by the selective reduction of the ω-ester with DIBAL^® under controlled conditions. The semialdehydes are chemically stable for a prolonged time and react with various phosphorous ylides, under controlled conditions, to produce the enantiomerically pure unsaturated α-amino acids in high yields. The method is equally applicable to homologated diesters obtained by the presented methodology providing unsaturated amino acids with variable unsaturated positions and geometries. The corresponding saturated products can be obtained by simple hydrogenation.