A re-statement of the Hohenberg–Kohn theorem and its extension to finite subspaces

Bearing in mind the insight into the Hohenberg–Kohn theorem for Coulomb systems provided recently by Kryachko (Int J Quantum Chem 103:818, 2005), we present a re-statement of this theorem through an elaboration on Lieb’s proof as well as an extension of this theorem to finite subspaces. Contribution to the Serafin Fraga Memorial Issue.     

Organocatalytic Michael addition, a convenient tool in total synthesis. First asymmetric synthesis of (−)-botryodiplodin

The asymmetric Michael addition of propionaldehyde to (2E)-(3-nitro-but-2-enyloxymethyl)-benzene 8, catalyzed by the chiral diamine (S,S)-N-iPr-2,2′-bipyrrolidine, afforded, with 93% ee, a precursor 9 of (−)-botryodiplodin. The nitro functionality of 9 was converted to a ketone via a Nef reaction to give, after a few steps, the enantiomerically enriched (−)-botryodiplodin.     

Dynamical systems theory for music dynamics

We show that, when music pieces are cast in the form of time series of pitch variations, the concepts and tools of dynamical systems theory can be applied to the analysis of temporal dynamics in music. (i) Phase space portraits are constructed from the time series wherefrom the dimensionality is evaluated as a measure of the global dynamics of each piece. (ii) Spectral analysis of the time series yields power spectra ( approximately f(-nu)) close to red noise (nu approximately 2) in the low frequency range. (iii) We define an information entropy which provides a measure of the local dynamics in the musical piece; the entropy can be interpreted as an evaluation of the degree of complexity in the music, but there is no evidence of an analytical relation between local and global dynamics. These findings are based on computations performed on eighty sequences sampled in the music literature from the 18th to the 20th century. (c) 1995 American Institute of Physics.     

On the use of relative deceleration values for the determination of silicon by PIGE

By spiking the samples with a compound containing both a non-analyte and an analyte element, to which a relative deceleration property for 5 Me V protons has been ascribed, relative deceleration values for the samples could be obtained by measuring the prompt -yields induced in the non-analyte element. These values are used to correct for matrix effects in elemental analysis using PIGE techniques. In addition to this, the analytical results thus obtained can also be compared to those obtained by the simultaneous application of the analyte spiking technique to the collected yield data. These non-analyte spiking approaches were used to analyze silicon in polymer materials. These methods were tested by analyzing the two reference standards BCS 308 and Standard Chrome Ore XXXI. Li₂SiO₃, containing both the non-analyte as well as the analyte element, was selected as comparator and spike. Results obtained for the polymer samples were also compared to those obtained by PIXE.     

Star-shaped azo-based dipolar chromophores: design, synthesis, matrix compatibility, and electro-optic activity

Three new azo-benzene-based push-pull chromophores with dendritic architecture were synthesized as active materials for electro-optic applications. These chromophores were synthesized in six or seven synthetic steps with an overall yield of around 80% per step and high purity. UV-vis spectroscopy showed significant influence of the transient dipole moment on the observed r(33) values. The chromophores were stable to photochemical oxidation in ambient light and air. The electrical poling conditions were optimized for each chromophore as the T(g) of the composite material varied significantly. The highest EO coefficient achieved was 22-25 pm/V at 1550 nm wavelength. STEM analysis of the blends enabled the correlation of the activity of these large chromophores with the blend morphology. An amorphous polycarbonate host effectively disperses the chromophores in 2-20 nm aggregates in the active materials. However, macrophase separation into 200-500 nm aggregates was observed in a methacrylate host matrix.     

Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition

Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.     

Comparison of quantitative methods for analysis of polyphasic pharmaceuticals

Adequate very sensitive quantification methods are needed for the development and are also now required for the monitoring of undesirable solid form(s) as routine tests. The pre-requisite for quantitation are selectivity, sensitivity and most important the purity of standards and their proper storage, what is a challenge for metastable forms. Several analytical techniques are available such as X-ray diffraction, spectroscopy, thermal analysis and microcalorimetry. The different steps of the validation of the analytical methods and problems to be solved are discussed. Examples illustrate the different techniques and compare their possible advantages and limits. The relative standard deviation of measurements should allow for checking the homogenization procedure of mixtures for calibration. The validation should be carried out following ICH guidelines for validation of analytical methods. Comparison of different techniques in adequate concentration range add confidence in the analytical results.     

Fabrication of "hairy" colloidosomes with shells of polymeric microrods

Novel colloidosome microcapsules with aqueous gel cores and integral shells of rodlike polymeric particles have been prepared and characterized. The synthesis is based on templating water-in-oil emulsions stabilized by rodlike particles followed by gelling of the aqueous phase, dissolution of the oil phase in ethanol, and redispersion of the obtained colloidosome capsules in water. Such capsules may find applications as vehicles for delivery and controlled release of drugs, cosmetics, and food supplements.     

Conformational analysis of a stereochemically complete set of cis-enediol peptide analogues

A conformational analysis of a stereochemically complete set of peptide analogues based on a cis-enediol unit is presented. The cis-enediol unit, which can replace a two or a three amino acid segment of a peptide, contains two "side chains", four asymmetrical carbon atoms, and six free dihedral angles. To determine the accessible conformational space, the molecules are divided into three fragments, each containing two free dihedral angles. The energy surfaces are computed for all dihedral angle values, and the possible conformations of the cis-enediol unit analogues are built using all combinations of the surface minima. Such a "build-up" procedure, which is very fast, is able to reproduce 75% of the minima obtained from a full dihedral angle exploration of the conformational space. The cis-enediol unit minima are compared with the corresponding di- and tripeptide minima; all peptide minima can be closely matched by a cis-enediol unit minimum of low energy (less than 2.2 kcal/mol above the lowest energy conformer). However, there are low energy minima of the cis-enediol unit that have no corresponding minima in peptides. The results are shown to depend strongly on the chirality of the analogues. The ability of each of the stereoisomers to mimic natural peptides, evaluated by the present approach, is correlated with its experimental activity in a renin inhibition assay.     

Highly efficient antibody-catalyzed deuteration of carbonyl compounds

Antibody 38C2 efficiently catalyzes deuterium-exchange reactions at the alpha position of a variety of ketones and aldehydes, including substrates that have a variety of sensitive functional groups. In addition to the regio- and chemoselectivity of these reactions, the catalytic rates (kcat) and rate-enhancement values (kcat/kun) are among the highest values ever observed with catalytic antibodies. Comparison of the substrate range of the catalytic antibody with highly evolved aldolase enzymes, such as rabbit-muscle aldolase, highlights the much broader practical scope of the antibody, which accepts a wide range of substrates. The hydrogen-exchange reaction was used for calibration and mapping of the antibody active site. Isotope-exchange experiments with cycloheptanone reveal that the formation of the Schiff base species (as concluded from the 16O/18O exchange rate at the carbonyl oxygen) is much faster than the formation of the enamine intermediate (as concluded from the H/D exchange rate), and both steps are faster than the antibody-catalyzed aldol addition reaction.