Synthetic Studies on Sialoglycoconjugates 49: Novel Disaccharides and Lactams Composed of Sialic Acid and 1-Deoxynojirimycin-Potential for Biomedical Application

Abstract

Sialic acid-containing glycoconjugates participate in a variety of biological functions on cell surfaces, not only serving as receptors for hormones, viruses and bacteria but also as mediators in cell growth, differentiation, adhesion, oncogenesis and so on. For example, influenza virus^1,2 and tripanosoma cruzi ^3,4 recognize sialic acid in the time of infection to animal cells. Recently, the sialyl-Le^x (sLe^x) and sialyl-Le^a (sLe^a) carbohydrate epitopes have been highlighted as the ligands for selectins, a family of cell adhesion molecules involved in leukocyte traffic^5,6 and tumor metastasis.⁷ 1-Deoxynojirimycin (DNJ) and related compounds are well known⁸ as the potent inhibitors of a-glycosidases and glycoprotein-processing enzymes. Some of the Nsubstituted DNJ derivatives have been noted as antidiabetic and anti-HIV agents.     

In cation interactions with some organics: ab initio molecular orbital and density functional theory

Ab initio molecular orbital and density functional theory studies were undertaken to investigate the structural and energetic characteristics of complexes of In⁺ with several different organic molecules for the first time. HF, MP2, QCISD, and CCD levels of theory in ab initio MO as well as B3LYP, B3PW91 hybrid functionals in density functional theory were used. A valence TZ+P basis set with relativistic effective core potentials was used for the In atom while the 6-311++G(3d, 2p) basis set was utilized for all other atoms. Both closed-shell (H₂O, CH₄, CH₃OH, and C₆H₆) and open-shell (CH₃ and C₂H₃) molecules were considered for complexation with In⁺. In⁺ affinities of 21.5, 24.8, 28.6, 18.4, and 23.0 kcal/mol were obtained with the B3PW91 hybrid functional for H₂O, CH₃OH, C₆H₆, CH₃, and C₂H₃, respectively. The large values for the calculated affinities indicate the validity of our recent experimental detection of In⁺ ion attachment to some organic molecules.     

Theoretical study of intramolecular interaction energies during dynamics simulations of oligopeptides by the fragment molecular orbital-Hamiltonian algorithm method

We analyzed the interaction energies between residues (fragments) in an oligopeptide occurring during dynamic simulations by using the fragment molecular orbital-Hamiltonian algorithm (FMO-HA) method, an ab initio MO-molecular dynamics technique. The FMO method enables not only calculation of large molecules based on ab initio MO but also easy evaluation of interfragment interaction energies. The glycine pentamer [(Gly)(5)] and decamer [(Gly)(10)] were divided into five and ten fragments, respectively. alpha-helix structures of (Gly)(5) and (Gly)(10) were stabilized by attractive interaction energies owing to intramolecular hydrogen bonds between fragments n and n+3 (and n+4), and beta-strand structures were characterized by repulsive interaction energies between fragments n and n+2. We analyzed interfragment interaction energies during dynamics simulations as the peptides' geometries changed from alpha helix to beta strand. Intramolecular hydrogen bonds between fragments 2-4 and 2-5 control the geometrical preference of (Gly)(5) for the beta-strand structure. The pitch of one turn of the alpha helix of (Gly)(10) elongated and thus weakened during dynamics due to a shifting of the intramolecular hydrogen bonds, and enabled the beta-strand structure to form. Changes in interaction energies due to the intramolecular hydrogen bonds controlled the tendency toward alpha-helix or beta-strand structure of (Gly)(5) and (Gly)(10). Evaluation of interfragment interaction energies during dynamics simulations thus enabled detailed analysis of the process of the geometrical changes occurring in oligopeptides.     

Intelligent colloidal hybrids via reversible pH-induced complexation of polyelectrolyte and silica nanoparticles

We present novel intelligent colloidal polymer/silica nanocomposites, in which the complexation of cationic silica nanoparticles and a weak anionic polyelectrolyte can be manipulated simply by pH change through a hydrogen-bonding interaction and ionic complexation caused by hydrogen-transfer interactions between the constituents. Special silica particles which have nanometer size (diameter approximately 3.0 nm) and two independent proton-accepting sites were developed in this study. Both the silica and poly(acrylic acid) form transparent colloidal solutions in water, while a white turbid dispersion was obtained just after mixing the two solutions due to the complexation. The pH-induced association-dissociation behavior was confirmed by the turbidity and potentiometric titration measurements. The assembled structures of the hybrids were visualized by scanning force microscopy.     

Fluorescence study of thermotropic liquid-crystalline polyesters

Photoluminescence behavior (polarization, lifetime) related to liquid-crystal (LC) formation was examined for the thermotropic liquid-crystalline polyesters poly [(ethylene terephthalate)-co-(p-oxybenzoate)] (PET40/OBA60) (OBA content: 60 mol %) and poly [(ethylene 2,6-naphthalene dicarboxylate)-co-(p-oxybenzoate)] (PEN50/OBA50) (OBA:50 mol %). The Growth of liquid-crystalline (LC) phases of PET40/OBA60 proceeded during annealing. even at low temperature (e.g., 138°C) and were promoted by an increase in annealing temperatures T_a in the experimental temperature range 138–260°C. The concentration dependence of fluorescence spectra of PET40/OBA60 in solution suggested that the fluorescences at 325 and 395 nm can be attributed to monomer and ground-state dimer, respectively. The increase in dimer fluorescence intensity and the decrease in the fluorescence anisotropy ratio r from 0.06 to –0.14 were observed with growth of LC phases. These effects are explained by an increase in the ground-state dimer population and a slight change in the dimer configuration, respectively. PEN50/OBA50 showed monomer fluorescence at 395 nm due to naphthalenedicarboxylate segments and excimer fluorescence at 430 nm. The r value for the excimer fluorescence decreased from zero to about ?0.14 with growth of the LC phase. Such an extraordinary phenomena, in comparison with the usual excimer fluorescences which occurs through energy migration, could be interpreted as the result of formation of high-concentration excimer sites induced by chain orientation in LC domains. © 1993 John Wiley & Sons, Inc.     

High-pressure (up to 140 MPa) density and derivative properties of some (pentyl-, hexyl-, and heptyl-) amines between (293.15 and 353.15) K

This work reports the density data (315 points) of a series of amines consisting of pentylamine, hexylamine, and heptylamine at seven temperatures between (293.15 and 353.15) K, and pressures up to 140 MPa (every 10 MPa) which allows to study the influence of the chain length. A new Anton-Paar vibrating tube densimeter, calibrated with water and vacuum with an uncertainty of ±5 · 10^?4 g · cm^?3 was used to perform these measurements. The experimental density data were fitted with the Tait-like equation with low standard deviations. In addition, the isobaric thermal expansivity and the isothermal compressibility have been derived from this equation.     

The synthesis of 1-thia-6-oxa-6alambda(4)-seleno-3-azapentalene and a 3H-1,2,4-dithiazole

The reaction of thiocarbamoyl isoselenocyanate with a carbanion gave 1-thia-6-oxa-6alambda(4)-seleno-3-azapentalene, which has a hypervalent selenium, as the major product. The by-products 3-diacylmethylidene-5-dimethylamino-3H-1,2,4-dithiazole and thiocarbamate thioanhydride were also formed.     

Synthesis of novel selenapenams, selenacephems, and selenazepines using a 2-(trimethylsilyl)ethyl protection approach

Selenapenams, selenacephems, and selenazepines were synthesized using a 2-(trimethylsilyl)ethyl (TSE) protection approach in an extremely simple way. TSE protection for selenium is used for the first time in the synthesis of selenium-containing beta-lactam. Novel intramolecular cycloaddition reaction of selenium with alkynes and allenes is used in the present synthesis.