Regioselectivity of olefin oxidation by iodosobenzene catalyzed by metalloporphyrins : control by the catalyst

The regioselectivity of the oxidation of three monosubstituted olefins, 6-phenoxyhex-1-ene, hex-1-ene and styrene, by iodosobenzene in the presence of various Fe-, Mn- or Cr-tetraaryl-porphyrins, was studied. It was found that, besides epoxides, known products from such systems, allylic alcohols and aldehydes were formed, the latter not being derived from the corresponding epoxides. The relative importance of these reactions greatly depends upon both the metal and porphyrin constituents of the catalyst. More particularly, the competition between epoxidation and allylic hydroxylation can be efficiently controlled by non-bonded interactions between the olefin and porphyrin substituents. No hydroxylation of the aromatic rings and no oxidative dealkylation of the ether function was detected.     

Multitargeting by curcumin as revealed by molecular interaction studies

Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca(2+) ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto-enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting binding sites, has also been used to further characterize curcumin's binding sites. Furthermore, the ability of curcumin to bind directly to carrier proteins improves its solubility and bioavailability. In this review, we focus on how curcumin directly targets signaling molecules, as well as the different forces that bind the curcumin-protein complex and how this interaction affects the biological properties of proteins. We will also discuss various analogues of curcumin designed to bind selective targets with increased affinity.     

DNA damage by sulfite autoxidation catalyzed by cobalt complexes

DNA damage was investigated in the presence of sulfite, dissolved oxygen and cobalt(II) complexes with glycylglycylhistidine, glycylhistidyllysine, glycylglycyltyrosylarginine and tetraglycine. These studies indicated that only Co(II) complexed with glycylglycylhistidine (GGH) induced DNA strand breaks at low sulfite concentrations (1-80 microM) via strong oxidants formed in the reaction. In the presence of the other complexes, some damage occurred only in the presence of high sulfite concentrations (0.1-2.0 mM) after incubation for 4 h. In the presence of GGH, Co(II) and dissolved O2, DNA damage must involve a reactive high-valent cobalt complex. The damaging effect was increased by adding S(IV), due to the oxysulfur radicals formed as intermediates in S(IV) autoxidation catalyzed by the complex. SO3 -, HO and H radicals were detected by EPR-spin trapping experiments with DMPO (5,5-dimethyl-1-pyrroline N-oxide). The results indicate that Co(II) binds O2 in the presence of GGH, and leads to the formation of a DMPO-HO adduct without first forming free superoxide or hydroxyl radical, supporting the participation of a reactive high-valent cobalt complex.     

Antibiotic recognition by binuclear metallo-beta-lactamases revealed by X-ray crystallography

Metallo-beta-lactamases are zinc-dependent enzymes responsible for resistance to beta-lactam antibiotics in a variety of host bacteria, usually Gram-negative species that act as opportunist pathogens. They hydrolyze all classes of beta-lactam antibiotics, including carbapenems, and escape the action of available beta-lactamase inhibitors. Efforts to develop effective inhibitors have been hampered by the lack of structural information regarding how these enzymes recognize and turn over beta-lactam substrates. We report here the crystal structure of the Stenotrophomonas maltophilia L1 enzyme in complex with the hydrolysis product of the 7alpha-methoxyoxacephem, moxalactam. The on-enzyme complex is a 3'-exo-methylene species generated by elimination of the 1-methyltetrazolyl-5-thiolate anion from the 3'-methyl group. Moxalactam binding to L1 involves direct interaction of the two active site zinc ions with the beta-lactam amide and C4 carboxylate, groups that are common to all beta-lactam substrates. The 7beta-[(4-hydroxyphenyl)malonyl]-amino substituent makes limited hydrophobic and hydrogen bonding contacts with the active site groove. The mode of binding provides strong evidence that a water molecule situated between the two metal ions is the most likely nucleophile in the hydrolytic reaction. These data suggest a reaction mechanism for metallo-beta-lactamases in which both metal ions contribute to catalysis by activating the bridging water/hydroxide nucleophile, polarizing the substrate amide bond for attack and stabilizing anionic nitrogen intermediates. The structure illustrates how a binuclear zinc site confers upon metallo-beta-lactamases the ability both to recognize and efficiently hydrolyze a wide variety of beta-lactam substrates.     

Glycosidase inhibition by macrolide antibiotics elucidated by STD-NMR spectroscopy

A glycosynthase approach was attempted to glycodiversify macrolide antibiotics, using DesR, a family-3 retaining beta-glucosidase involved in the self-resistance mechanism of methymycin production. STD-NMR was used to probe enzyme-substrate interactions. Analysis of competitive STD-NMR experiments between erythromycin A and a chromogenic substrate (pNP-beta-d-glucose) with the hydrolytically inactive nucleophile mutants led us to discover a family of unprecedented glycosidase inhibitors. Analysis of kinetic data with wild-type DesR determined that erythromycin is a competitive inhibitor of the glucosidase (IC50 = 2.8 +/- 0.3 microM and Ki = 2 +/- 0.2 microM) with respect to the hydrolysis of pNP-beta-d-glucose. Comparable inhibitory data was obtained for clarithromycin; however, the inhibitory effect of azithromycin was weak and no significant inhibition was observed with methymycin or d-desosamine. This report documents significant inhibition of glycosidases by macrolide antibiotics and provides insight into the design of novel glycosidase inhibitors based on the macrolactone ring of macrolide antibiotics.     

Membrane solubilization by detergent: resistance conferred by thickness

The commonly held model for membrane dissolution by detergents/surfactants requires lipid transport from the inner to the outer bilayer leaflet ('flip-flop'). Although applicable to many systems, it fails in cases where cross-bilayer transport of membrane components is suppressed. In this paper we investigate the mechanism for surfactant-induced solubilization of polymeric bilayers. To that end, we examine the dissolution of a series of increasingly thick, polymer-based vesicles (polymersomes) by a nonionic surfactant, Triton X-100, using dynamic light scattering. We find that increasing the bilayer thickness imparts better resistance to dissolution, so that the concentration required for solubilization, after a fixed amount of time, increases nearly linearly with membrane thickness. Combining our experimental data with a theoretical model, we show that the dominant mechanism for the surfactant-induced dissolution of polymeric vesicles, where polymer flip-flop across the membrane is suppressed, is the surfactant transport through the bilayer. This mechanism is different both qualitatively and quantitatively from the mechanisms by which surfactants dissolve pure lipid vesicles.     

Flocculation mechanism induced by cationic polymers investigated by light scattering

Three cationic polymers with molecular weights and charge densities of 3.0 x 10(5) g/mol and 10%, 1.1 x 10(5) g/mol and 40%, and 1.2 x 10(5) g/mol and 100% were chosen as flocculants to aggregate silica particles (90 nm), under various conditions, including change in polymer dosage, particle concentration, background electrolyte concentration, and shear rate. The size and structure of flocs produced were determined using the static light scattering technique. On the basis of measurements of polymer adsorption and its effect on the zeta potential and floc properties, it has been found that the polymer charge density plays an important role in determining the flocculation mechanism. Polymers with a 10% charge density facilitate bridging, 40% charged polymers bring about either a combination of charge neutralization and bridging or bridging, depending on the polymer dosage, and polymers with the charge density of 100% induce electrostatic patch flocculation mechanism at the optimum polymer dosage and below but bring about bridging mechanism at the polymer dosage approaching the adsorption plateau value. Bridging aggregation can readily be affected by the particle concentration, and an increase in particle concentration results in the formation of larger but looser aggregates, whereas electrostatic patch aggregation is independent of particle concentration. The addition of a background electrolyte aids in bridging aggregation while it is detrimental to electrostatic patch aggregation. It has also been found that the effect of shear rate on the mass fractal dimension depends on polymer charge density.     

Nanoporous carbons obtained by carbonization of copolymers impregnated by salts

This paper demonstrates the results of research on influence of types of polymer and kinds of salts used for impregnation of the polymer on porous structure formation in the final carbonaceous product. The studies were performed in two stages. In the first stage, the role of polymer structure were mainly studied. To achieve the aim, three different porous copolymers (polyimide and two types of polyester) were impregnated with the same salts (NiSO₄, and the mixture of AgNO₃ and Gd(NO₃)₃). In the second part of the study, only one polymer (polyimide) was impregnated by three mixtures of salts (chlorides, nitrates and sulphates of K, Cu(II) and Fe(III)). This approach allowed to evaluate the impact of the mixture of salts on porosity of the carbons, which were to be prepared. The obtained results revealed that when the impregnation was applied as a method for activation and moulding of porosity of carbonaceous materials prepared from polymers, several factors should be taken into account. First of all, initial decomposition temperatures of the polymers and the salts should be compared to find out if carbonization and activation processes proceed simultaneously or not. If the copolymer was carbonized and gases were released from decomposing salts, they reacted each other and synergic effect of polymer and salts properties were observed. Such conditions favored the development of microporous structure of the obtained carbon. On the contrary, if the processes were separated in time because of high temperature of melting point of the salts more mesopores were retained.     

Photoprotection by melanin

This paper is an attempt to summarize the current state of information on melanin and epidermal melanin pigmentation (EMP) as photoprotective agents. The chemistry and biochemistry of melanin (the particle) and its interaction, in its various forms, with UV radiation are considered. Methods of attenuation of UV radiation are discussed in terms of structure and chemical constituents. Photoprotection by constitutive and facultative pigmentation is reviewed with minimum erythema dose (MED) as the end point. The issue of acclimatization to UV radiation is discussed in terms of UVB phototherapy for psoriasis. Finally, skin cancer is considered as an end point and the reduction of its incidence with pigment level is discussed. It is concluded that whilst EMP provides protection, its extent depends on the end point chosen for evaluation. MED is a convenient photobiological end point but is rather insensitive, whereas skin cancer is sensitive but impractical for laboratory studies. Our current state of knowledge of melanin lacks information on its absorption and scattering coefficients and its refractive index. Methods for the quantitative measurement of EMP are also urgently required.     

Analysis by calorimetry

The last years have seen the development of differential calorimetry into a scanning technique for routine analysis. In order of ease of determination heats of fusion, heats of reaction, phase diagrams, purity analysis, heat capacity and similar heat effects are added to the list of quickly measurable quantities. Accuracies of the order of 1–5% of heats of fusion and heat capacity are obtainable under favorable conditions. Special topics which have been discussed are instrumentation, transition temperatures, heat capacities, glass transitions, heats of transitions, and phase diagrams.     

Production of Enzymes by Plant Cells Immobilized by Sol-Gel Silica

Ajuga reptans cells are cultivated and used for production of invertase. These plant cells are immobilized by a sol-gel SiO₂ membrane, which is built up directly on the cell surface by exposure to a gaseous flow of silicon alcoxide precursors. The immobilization modifies the metabolic activity of cells, resulting in a 40-fold increase in invertase production with respect of free cells. Results concerning total release of proteins, cell growth and produced invertase activity are discussed, considering the absence of breeding, induced by SiO₂ immobilization, the prominent factor promoting the observed exceptional increase in invertase productivity.     

Crystal nucleation given rise by fracturing or by mechanical shock

Summary Sudden crystallization takes place frequently in supercooled liquids or in supersaturated solutions (usually of ionic compounds) when solid substances immersed in the liquids are cut or fractured mechanically. Rupture of chemical bonds in the solid is essential for the nucleation and the effect disappears momentarily. Crystallization is also frequently given rise by mechanical shock in the above mentioned liquids, and may be explained as follows: electrons of the shocked molecules become labile and may behave like free electrons in metals momentarily as demonstrated experimentally. Generated free radicals and free electrons cluster into a metal-like structure and are compressed into the closest-packed structure with higher regularity by forces analogous to metallic bond. The cluster may act as the embryo and the nucleus of the crystal, if its structure resembles to that of the crystal or if it is easily convertable to the latter. Nucleation in supercooled liquids given rise by fracturing of solids is explained in an analogous way. Fractured surface of solids is momentarily covered with free radicals. The labile electrons and positively polarized part of liquid molecules in contact with the surface may form a two-dimensional metallic structure and the resulting compressed layer may act as the nucleus, if its structure is appropriate.

---

Zusammenfassung Plötzliche Kristallisation geschieht oft in unterkühlten Flüssigkeiten oder in übersättigten Lösungen (gewöhnlich von Ionenverbindungen), wenn feste Substanzen, die in die Flüssigkeiten eingetaucht sind, mechanisch geschnitten oder gebrochen werden. Die Spaltung der chemischen Bindungen in den festen Substanzen scheint notwendig für die Keimbildung zu sein. Plötzliche Kristallisation wird auch durch mechanische Erschütterung in den Flüssigkeiten hervorgerufen. Diese Phänomene werden durch Einfluß delokalisierter Elektronen auf die Keimbildung erklärt.

---

---

With 3 figures and 3 tables     

Quantitative Particle Uptake by Cells as Analyzed by Different Methods

There is a large number of two‐dimensional static in vitro studies about the uptake of colloidal nano‐ and microparticles, which has been published in the last decade. In this Minireview, different methods used for such studies are summarized and critically discussed. Supplementary experimental data allow for a direct comparison of the different techniques. Emphasis is given on how quantitative parameters can be extracted from studies in which different experimental techniques have been used, with the goal of allowing better comparison.     

Solubilization by polysoaps

The aqueous solubilization power of several series of micellar homopolymers and copolymers (polysoaps) is investigated. Using five insoluble or poorly water-soluble dyes, comparisons of the capacities are made with respect ot the influence of structural variables such as the polymer backbone, the polymer geometry, the comonomer content, and the charge of the hydrophilic group. Some guidelines for polysoap structures suited for efficient solubilization are established. Noteworthy is that the solubilization capacities of the polysoaps are neither linked to the ability to reduce the surface tension of water, nor to the polarity of the solubilization sites deduced from spectroscopic probes.     

Similarity by compression

We present a simple and effective method for similarity searching in virtual high-throughput screening, requiring only a string-based representation of the molecules (e.g., SMILES) and standard compression software, available on all modern desktop computers. This method utilizes the normalized compression distance, an approximation of the normalized information distance, based on the concept of Kolmogorov complexity. On representative data sets, we demonstrate that compression-based similarity searching can outperform standard similarity searching protocols, exemplified by the Tanimoto coefficient combined with a binary fingerprint representation and data fusion. Software to carry out compression-based similarity is available from our Web site at http://comp.chem.nottingham.ac.uk/download/zippity.     

Separation by Flotation

There has been much recent activity in the theory and application of separation by flotation, both in the United. States and abroad. This review primarily addresses new developments in foam flotation, colloid flotation and precipitate flotation. The work in ore flotation represents a major effort and would itself require a lengthy article. Work from ore flotation which significantly impacts on the areas of interest listed above is included here, however. Foam separation of biological materials and the microflotation of bacteria are not routinely discussed in this review. A few recent review articles on these areas are included at the end of the Review Articles and Books Section to afford the interested reader a start on that literature. The development and use of flotation separation techniques for waste treatment and water reuse over the last few years are included in this article.     

Desymmetrization of Dicationic Diboranes by Isomerization Catalyzed by a Nucleophile

Cationic monoboranes exhibit a rich chemistry. By constrast, only a few cationic diboranes are known, that all are symmetrically substituted. In this work, the first unsymmetrically substituted dicationic diboranes, featuring sp²–sp²‐hybridized boron atoms, are reported. The compounds are formed by intramolecular rearrangement from preceding isomeric symmetrically substituted dicationic diboranes, a process that is catalyzed by nucleophiles. From the temperature‐dependence of the isomerization rate, activation parameters for this unprecedented rearrangement are derived. The difference in fluoride ion affinity between the two boron atoms and the bonding situation in these unique unsymmetrical dicationic diboranes are evaluated.     

Kinetics of chalcone oxidation by peroxide anion catalysed by poly-l-leucine

An insight into the kinetics, mechanism and optimum reaction conditions of the Julia-Colonna epoxidation has been gained using a soluble polyleucine catalyst.     

Pretreatment of softwood by acid-catalyzed steam explosion followed by alkali extraction

A process for converting lignocellulosic biomass to ethanol hydrolyzes the hemicellulosic fraction to soluble sugars (i.e., pretreatment), followed by acid- or enzyme-catalyzed hydrolysis of the cellulosic fraction. Enzymatic hydrolysis may be improved by using an alkali to extract a fraction of the lignin from the pretreated material. The removal of the lignin may increase the accessibility of the cellulose to enzymatic attack, and thus improve overall economics of the process, if the alkali-treated material can still be effectively converted to ethanol. Pretreated Douglas fir produced by a sulfuric-acid-catalyzed steam explosion was treated with NaOH, NH₄OH, and lime to extract some of the lignin. The treated material, along with an untreated control sample, was tested by an enzymatic-digestion procedure, and converted to ethanol by simultaneous saccharification and fermentation using a glucose-fermenting yeast. NaOH was most effective at removing lignin (removed 29%), followed by NH4OH and lime. However, the susceptibility of the treated material to enzymatic digestion was lower than the control and decreased with increasing lignin removal. Ethanol production was similar for the control and NaOH-treated material, and lower for NH₄OH- and lime-treated material.     

Aqueous nanostructures in water induced by electromagnetic fields emitted by EDS

This article reports the experimental results of a conductometric study on the time evolution, over a 541-day period, of 450 samples of Extremely Diluted Solutions (EDS) of fullerene and carbon nanotube and 450 samples of twice-distilled water, stored in alternate rows of EDS and water spaced 0.5 cm apart. The purpose was to establish whether these two aqueous systems are able to transmit, via electromagnetic fields, their variations in the supramolecular structure of the solvent water which has not undergone any previous perturbation. The chemical-physical method employed was conductometry, which proved to be the simplest and most efficient means for quickly and accurately monitoring the structural variations. In addition, since it has been demonstrated that there is a clear linear correlation between specific conductivity and heat of mixing with alkaline solutions, the conductometric result can also be extended to the calorimetric result. These findings, though doubtless unexpected and intriguing, are highly significant. The alterations over time of the pure water samples follow those of the EDS surprisingly closely.