Réactivité de l’acide déhydroacétique hydrogené en c5-c6 : obtention des pyrano-1,5-benzodiazépines différemment substituées et de la structure enaminone

A number of 1,5-benzodiazepines derivatives 4 were obtained via the interaction of dehydroacetic acid hydrogenated at C₅-C₆, orthophenylenediamines and aromatic aldehydes. The interpretation of the results is enriched by a study of the electronic effects of the DHA hydrogenated at C₅-C₆. Accordingly, it leads us to obtain the original structure cynnamoyle 5.     

Reactivity studies on 4‐aminopyrones: Access to benzimidazole and benzimidazolone derivatives

Reaction of pyrone 1a or tetronic acid 1b with o‐phenylenediamine derivatives gave enaminone compounds 2 . When reacting with different electrophiles, these intermediates allowed versatile access to different heterocyclic structures: when DMA derivatives or triphosgene was used, cyclization occurred through nitrogen, leading to benzimidazoles 3 and benzimidazolones 4 , respectively, while reaction with benzaldehyde yielded benzodiazepines 5 .     

Differential geometry of edgeworth expansions in curved exponential family

Summary In order to construct a higher-order asymptotic theory of statistical inference, it is useful to know the Edgeworth expansions of the distributions of related statistics. Based on the differential-geometrical method, the Edgeworth expansions are performed up to the third-order terms for the joint distribution of any efficient estimators and complementary (approximate) ancillary statistics in the case of curved exponential family. The marginal and conditional distributions are also obtained. The roles and meanings of geometrical quantities are elucidated by the geometrical interpretation of the Edgeworth expansions. The results of the present paper provide an indispensable tool for constructing the differential-geometrical theory of statistics.     

Triple-point wetting on rough substrates

The influence of substrate roughness on the wetting scenario of adsorbed van der Waals films is investigated by theory and experiment. Calculating the bending free energy penalty of a solid sheet picking up the substrate roughness, we show that a finite roughness always leads to triple-point wetting reducing the widths of the adsorbed solid films considerably as compared to that of smooth substrates. Testing the theory against our experimental data for molecular hydrogen adsorbed on gold, we find quantitative agreement.     

Fragment interaction analysis based on local MP2

We have developed a fragment interaction analysis based on local MP2 (FILM) in the context of the fragment molecular orbital (FMO) scheme. The primary purpose of this work is to provide a tool for analyzing inter-fragment interaction associated with dispersion interactions in a large molecule such as protein and DNA. Our implementation of local MP2 (LMP2) is based on the algorithm developed by Pulay and Werner. A potential of FILM was demonstrated using the human immunodeficiency virus type 1 protease (HIV-1 PR) complexed with lopinavir (LPV). The total energy, binding affinity, and inter-fragment interaction energy (IFIE) by the FMO method using LMP2 were compared with those obtained by canonical MP2 and the site-specific information in dispersion interaction was obtained. It turned out that the FILM is a useful tool for analyzing the dispersion interaction between an amino acid residue and a specific site of a ligand.     

In situ synthesis of silver nanoparticles on densely amine‐functionalized polystyrene: Highly active nanocomposite catalyst for the reduction of methylene blue

In this contribution, polystyrene (PS) bearing nitrogen‐rich ligands as chelation moieties for both Ag⁺ ions and Ag⁽⁰⁾ nanoparticles was prepared through successive chemical modifications of native PS including nitration (treatment with HNO₃/H₂SO₄), reductive amination (treatment with SnCl₂/HCl), Michael addition of methyl acrylate, and grafting of ethyelenediamine. The as‐synthesized PS derivative was further used to support silver nanoparticles through initial chelation of the silver nanoparticle ions precursor and subsequent chemical in situ reduction with sodium borohydride. Chemical structure of the PS derivatives was confirmed after each synthesis step by using complementary characterization methods including infrared and energy‐dispersive X‐ray spectroscopies, elemental analysis, X‐ray diffraction, thermogravimetric analysis, and scanning electron microscopy. The catalytic activity of the PS‐EAD/AgNP nanocomposite was demonstrated using the reduction of methylene blue to leucomethylene blue, as a model reaction. The reaction was monitored by UV‐vis spectrophotometry and achieved with an excess of sodium borohydride allowing for a pseudo‐first‐order analysis of the kinetic reaction parameters. Quantitative reduction of the methylene blue was obtained upon successive catalytic cycles with a rate constant value of 0.4016 minute^?1.     

Development of KiBank, a database supporting structure-based drug design

KiBank is a database of inhibition constant (K_i) values with 3D structures of target proteins and chemicals. K_i values were accumulated from peer-reviewed literature searched via PubMed. The 3D structure files of target proteins were originally from Protein Data Bank (PDB), while the 2D structure files of the chemicals were collected together with the K_i values and then converted into 3D ones. In KiBank, the chemical and protein 3D structures with hydrogen atoms were optimized by energy minimization and stored in MDL MOL and PDB format, respectively.

KiBank is designed to support structure-based drug design. It provides structure files of proteins and chemicals ready for use in virtual screening through automated docking methods, while the K_i values can be applied for tests of docking/scoring combinations, program parameter settings, and calibration of empirical scoring functions. Additionally, the chemical structures and corresponding K_i values in KiBank are useful for lead optimization based on quantitative structure–activity relationship (QSAR) techniques.

KiBank is updated on a daily basis and is freely available at http://kibank.iis.u-tokyo.ac.jp/. As of August 2004, KiBank contains 8000 K_i values, over 6000 chemicals and 166 proteins covering the subtypes of receptors and enzymes.     

Strain-thickening transition in ferric-oxide suspensions under oscillatory shear

Shear-strain-thickening transition under oscillatory flow was observed in flocculated ferric-oxide suspensions in mineral oil. The value of the dynamic modulus of the suspensions that was measured at small strain amplitude after cessation of shear also became higher when the strain amplitude of the applied shear had been within or above the transition region.The ferric-oxide powders used were an acicular submicron maghemite (magnetic) and the hematite (non-magnetic) that was converted from the maghemite by heat treatment. The powders were treated with a dispersing agent and the suspensions were prepared in 33% by particle weight. The strain-thickening transition was observed in both the magnetic and the non-magnetic suspensions. However, the onset of the strain-thickening in the magnetic suspension was found at about one decade larger strain amplitude than that in the non-magnetic analog suspension, indicating particle interactions affect to the appearance of the phenomenon.A qualitative interpretation was made in view of site percolation for the enhancement of modulus at rest after the application of the large-amplitude oscillatory shear, where the process of the strain-thickening transition under shear and the development of the modulus after stopping the shear was described with a floc model in which the flocculation phase dilates as a result of the reduction of the particle linkages under higher shear.     

VISCANA: visualized cluster analysis of protein-ligand interaction based on the ab initio fragment molecular orbital method for virtual ligand screening

We have developed a visualized cluster analysis of protein-ligand interaction (VISCANA) that analyzes the pattern of the interaction of the receptor and ligand on the basis of quantum theory for virtual ligand screening. Kitaura et al. (Chem. Phys. Lett. 1999, 312, 319-324.) have proposed an ab initio fragment molecular orbital (FMO) method by which large molecules such as proteins can be easily treated with chemical accuracy. In the FMO method, a total energy of the molecule is evaluated by summation of fragment energies and interfragment interaction energies (IFIEs). In this paper, we have proposed a cluster analysis using the dissimilarity that is defined as the squared Euclidean distance between IFIEs of two ligands. Although the result of an ordered table by clustering is still a massive collection of numbers, we combine a clustering method with a graphical representation of the IFIEs by representing each data point with colors that quantitatively and qualitatively reflect the IFIEs. We applied VISCANA to a docking study of pharmacophores of the human estrogen receptor alpha ligand-binding domain (57 amino acid residues). By using VISCANA, we could classify even structurally different ligands into functionally similar clusters according to the interaction pattern of a ligand and amino acid residues of the receptor protein. In addition, VISCANA could estimate the correct docking conformation by analyzing patterns of the receptor-ligand interactions of some conformations through the docking calculation.     

Geometry of deformed exponential families: Invariant,dually-flat and conformal geometries

An information-geometrical foundation is established for the deformed exponential families of probability distributions. Two different types of geometrical structures, an invariant geometry and a flat geometry, are given to a manifold of a deformed exponential family. The two different geometries provide respective quantities such as deformed free energies, entropies and divergences. The class belonging to both the invariant and flat geometries at the same time consists of exponential and mixture families. Theq$q$-families are characterized from the viewpoint of the invariant and flat geometries. The q$q$-exponential family is a unique class that has the invariant and flat geometries in the extended class of positive measures. Furthermore, it is the only class of which the Riemannian metric is conformally connected with the invariant Fisher metric.