Dramatic slowing down of the conformational equilibrium in the silyl derivative of glucose in the vicinity of the glass transition temperature.

The vitrification process is usually preceded by a significant change (around 6-8 decades) in the viscosity, structural relaxation times, or diffusion that occurs in a relatively small range of temperatures in fragile liquids. Along with this phenomenon, conformations of the molecules vary as well. In fact, this process is studied in bulk polymers and high molecular weight materials deposited in the form of thin films. On the other hand, spatial rearrangement of small glass formers in the supercooled liquid state has not been intensively investigated, so far. Herein, data obtained from measurements carried out using various experimental techniques on supercooled 1,2,3,4,6-penta-O-(trimethylsilyl)-d-glucopyranose (S-GLU) have revealed that rotations of silyl moieties along with the deformation in the saccharide ring are significantly slowed down in the vicinity of the glass transition temperature (Tg). These intramolecular reorganizations affect the structural relaxation time, atomic pair distribution function, integrated intensity, as well as a number of bands and signals observed, respectively, in the Raman and NMR spectra. Data reported herein offer a better understanding of the conformational variation and time scale of this process in the complex and flexible molecules around the Tg.

Synthetic Glycosides and Glycoconjugates of Low Molecular Weight Natural Products.

Enzymatically controlled transfer of saccharide moieties constitutes a fundamental biological process, essential for both primary and secondary metabolism. Natural products, including countless glycosides, with a rich tradition of use in ethnopharmacology, remain a prime source of inspiration for medicinal chemistry and molecular pharmacology, but their availability from biological sources is usually scarce, hampering attempts at application for new drug discovery and development. Chemical glycosylation on the other hand, although continuously undergoing sophisticated mechanistic studies, has nevertheless already matured as a set of methods which are able to provide substantial amounts of pure chemical entities: natural glycosides, as well as their congeners and mimics, necessary for the study of biological activity in quality assurance systems and required for drug development by pharmaceutical regulations. The paper presents a review of natural products and their analogues glycosylation, in a set of arbitrary selected examples, supplemented with comments on general advances in chemical glycosylation methodology and their applicability for particular categories of secondary metabolites.

Simple synthesis of glycosylthiols and thioglycosides by rearrangement of O-glycosyl thionocarbamates.

The synthesis of thioglycosides has been achieved in a high yielding process employing thionocarbamates prepared from protected reducing sugars and N-alkyl isothiocyanate in the presence of a non-nucleophilic base (K2CO3). In the key step of the synthesis, thionocarbamates were treated with Lewis acid (TMSOTf) to give O,S-rearrangement products that were applied to the synthesis of both anomers of heteroaryl thioglycosides.

Identifying the origins of two secondary relaxations in polysaccharides.

The main goal of this paper is to identify the molecular origins of two secondary relaxations observed in mechanical as well as in dielectric spectra in polysaccharides, including cellulose, and starches, such as pullulan and dextran. This issue has been actively pursued by many research groups, but consensus has not been reached. By comparing experimental data of monosaccharides, disaccharides, and polysaccharides, we are able to make conclusions on the origins of two secondary relaxations in polysaccharides. The faster secondary relaxations of polysaccharides are similar to the faster secondary relaxations of mono-, di-, and oligosaccharides. These include comparable relaxation times and activation energies in the glassy states, and also all the faster secondary relaxations have larger dielectric strengths than the slower secondary relaxation. The similarities indicate that the faster secondary relaxations in the polysaccharides have the same origin as that in mono-, di-, and oligosaccharides. Furthermore, since the relaxation time of the faster secondary relaxation in several mono- and disaccharides was found to be insensitive to applied pressure, the faster secondary relaxations of the polysaccharides are identified as internal motions within their monomeric units. The slower secondary relaxations in polysaccharides also have similar characteristics to those of the slower secondary relaxations of the disaccharides (maltose, cellobiose, sucrose, and trehalose), which indicates the analogous motions govern the slower process in these two groups of carbohydrates. Earlier we have shown in disaccharides that the rotation of the monomeric units around the glycosidic bond is responsible for this process. The same motion can occur in polysaccharides in the form of a local chain rotation. These motions involve the whole molecule in disaccharides and a local segment in polysaccharides. It is intermolecular in nature (with relaxation time pressure dependent, as found before in a disaccharide), and hence, it is the precursor of the structural alpha-relaxation. These results lead us to identify the slower secondary relaxation of the polysaccharides as the Johari-Goldstein beta-relaxation, which is supposedly a universal and fundamental process in all glass-forming substances.

Interaction of genistein benzyl derivatives with lipid bilayers--fluorescence spectroscopic and calorimetric study.

The purpose of the present paper was to assess the ability of genistein benzyl derivatives to interact with lipid bilayers. Calorimetric and fluorescence spectroscopic measurements revealed that, depending on the details of chemical structure, the studied compounds penetrated bilayers and affected their polar as well as hydrophobic regions. It was also found that physical state of bilayer played some role in flavonoid-lipid interactions.

Dielectric studies on mobility of the glycosidic linkage in seven disaccharides.

Isobaric dielectric relaxation measurements were performed on seven chosen disaccharides. For five of them, i.e., sucrose, maltose, trehalose, lactulose, and leucrose, we were able to observe the temperature evolution of the structural relaxation process. In the case of the other disaccharides studied (lactose and cellobiose), it was impossible to obtain such information because of the large contribution of the dc conductivity and polarization of the capacitor plates to the imaginary and real part of the complex permittivity, respectively. On the other hand, in the glassy state, two secondary relaxations have been identified in the dielectric spectra of all investigated carbohydrates. The faster one (gamma) is a common characteristic feature of the entire sugar family (mono-, di-, oligo-, and polysaccharide). The molecular origin of this process is still not unambiguously identified but is expected to involve intramolecular degrees of freedom as inferred from insensitivity of its relaxation time to pressure found in some monosaccharides (fructose and ribose). The slower one (labeled beta) was recently identified to be intermolecular in origin (i.e., a Johari-Goldstein (JG) beta-relaxation), involving twisting motion of the monosugar rings around the glycosidic bond. The activation energies and dielectric strengths for the beta-relaxation determined herein provide us valuable information about the flexibility of the glycosidic bond and the mobility of this particular linkage in the disaccharides studied. In turn, this information is essential for the control of the diffusivity of drugs or water entrapped in the sugar matrix.

Studies on the synthesis of 1,2-cis pentofuranosides from S-glycofuranosyl dithiocarbamates, dithiocarbonates and phosphorodithioates.

The selectivity in the synthesis of 1,2-cis glycofuranosides from dithiocarbonates, dithiocarbamates and phosphorodithioates is improved by combined use of silver triflate and catalytic amount of hexamethylphosphoramide (HMPA) under mild conditions.