Conformational dependence of pyranoid rings 1,2-cis-fused to dioxolane rings on the configuration of the dioxolane rings in acetylated derivati

X-Ray and ¹H N.M.R. studies on pyranoid rings 1,2-$\text{cis}$-fused to dioxolane rings in acetylated $\text{D}$-gluco- and $\text{D}$--galactopyranose derivatives demonstrate that the configuration of the dioxolane ring influences the conformation of the pyranoid ring in the $\text{D}$-gluco but not in the $\text{D}$-galactopyranose series. The crystal structure of 3,4,6-tri-$\text{O}$-acetyl-1,2-$\text{O}$-(R)--(l-cyano-ethylidene)-α-$\text{D}$-glucopyranose ($\text{1}$) and 3,4,6-tri-$\text{O}$-acetyl-1,2-$\text{O}$-($\text{R}$)-(1-cyano-ethylidene)-α-$\text{D}$-galactopyranose ($\text{2}$)have been determined by X-ray analysis. Lattice parameters for $\text{1}$ are a=20.6021 (11), b=8.0438 (2), c=5.5541 (1) Å and β= 95.588 (3)° for a cell with P21 symmetry. These parameters for $\text{2}$ are a=20.3361 (7), b=10.0907 (2), c=18.9115 (5) Å, β =112.399 (2)°, C2, with two crystallographycally independent molecules. The conformation of the pyranoid ring in both compounds can be described as flattened ⁴C₁ and that of the dioxolane ring as distorted E₁. The importance of the torsion angles for describing problems of configuration is remarked and the use of relative configurational angles is stressed. The ¹H N.M.R. spectra of $\text{1}$ and $\text{2}$ and 3,4,6-tri-$\text{O}$-acetyl-1,2-O-(S)- and (R)-ethylidene-α-$\text{D}$-glucopyranose ($\text{5}$ and $\text{7}$), 3,4,6-tri-O-acetyl--1,2-O-(S)- and ($\text{R}$)-ethylidene-α-$\text{D}$-galactopyranose ($\text{6}$ and $\text{8}$), and 3,4,6-tri-$\text{O}$-acetyl-1,2-$\text{O}$-($\text{S}$)-and ($\text{R}$)-benzylidene-α-$\text{D}$-glucopyranose ($\text{9}$ and $\text{10}$) have been analyzed by using iterative computer methods and N.O.E. measurements. The results indicate that the major solution conformation of the pyranoid ring of the derivatives in the $\text{D}$-gluco series $\text{1}$, $\text{5}$ and $\text{9}$ may be described as flattened ⁴C₁ and that of $\text{7}$ and $\text{10}$ as ²$\text{S}$₅. The major solution conformation of the pyranoid ring in all compounds in the $\text{D}$-galacto series ($\text{2}$,$\text{4}$,$\text{6}$,$\text{8}$) may be described as flattened ⁴$\text{C}$₁.     

Quantitation of a de‐fluorinated analogue of Casopitant Mesylate by normal‐phase liquid chromatography/mass spectrometry

The introduction of Quality by Design (QbD) in Drug Development has resulted in a greater emphasis on chemical process understanding, in particular on the origin and fate of impurities. Therefore, the identification and quantitation of low level impurities in new Active Pharmaceutical Ingredients (APIs) play a crucial role in project progression and this has created a greater need for sensitive and selective analytical methodology. Consequently, scientists are constantly challenged to look for new applications of traditional analytical techniques. In this context a normal‐phase liquid chromatography/electrospray ionization mass spectrometry (LC/ESI‐MS) method was developed to determine the amount of a de‐fluorinated analogue impurity in Casopitant Mesylate, a new API under development in GlaxoSmithKline, Verona. Normal‐phase LC provided the selectivity needed between our target analyte and Casopitant, while a single quadrupole mass spectrometer was used to ensure the sensitivity needed to detect the impurity at <0.05%w/w. Standard solutions and samples were prepared in heptane/ethanol (50:50, v/v) containing 1% of 2 M NH₃ in ethanol; the mobile phase consisted of heptane/ethanol (95:5, v/v) with isocratic elution (flow rate: 1.0 mL/min, total run time: 23 min). To allow the formation of ions in solutions under normal‐phase (apolar) conditions, a post‐column infusion of a solution of 0.1% v/v of formic acid in methanol was applied (flow rate: 200 µL/min). The analysis was carried out in positive ion mode, monitoring the impurity by single ion monitoring (SIM). The method was fully validated and its applicability was demonstrated by the analysis of real‐life samples. This work is an example of the need for selective and accurate methodology during the development of a new chemical entity in order to develop an appropriate control strategy for impurities to ultimately ensure patient safety. Copyright © 2010 John Wiley & Sons, Ltd.     

Nuclear Uptake of Gold Nanoparticles Deduced Using Dual‐Angle X‐Ray Fluorescence Mapping

Studies into the cell nucleus' incorporation of gold nanoparticles (AuNPs) are often limited by ambiguities arising from conventional imaging techniques. Indeed, it is suggested that to date there is no unambiguous imaging evidence for such uptake in whole cells, particularly at the single nanoparticle level. This shortcoming in understanding exists despite the nucleus being the most important subcellular compartment in eukaryotes and gold being the most commonly used metal nanoparticle in medical applications. Here, dual‐angle X‐ray flouresence is used to show individually resolved nanoparticles within the cell nucleus, finding them to be well separated and 79% of the intranuclear population to be monodispersed. These findings have important implications for nanomedicine, illustrated here through a specific exemplar of the predicted enhancement of radiation effects arising from the observed AuNPs, finding intranuclear dose enhancements spanning nearly five orders of magnitude.     

Deformed quantum double realization of the toric code and beyond

Quantum double models, such as the toric code, can be constructed from transfer matrices of lattice gauge theories with discrete gauge groups and parametrized by the center of the gauge group algebra and its dual. For general choices of these parameters the transfer matrix contains operators acting on links which can also be thought of as perturbations to the quantum double model driving it out of its topological phase and destroying the exact solvability of the quantum double model. We modify these transfer matrices with perturbations and extract exactly solvable models which remain in a quantum phase, thus nullifying the effect of the perturbation. The algebra of the modified vertex and plaquette operators now obey a deformed version of the quantum double algebra. The Abelian cases are shown to be in the quantum double phase whereas the non-Abelian phases are shown to be in a modified phase of the corresponding quantum double phase. These are illustrated with the groups Z_n${\mathbb{Z}}_n$ and S₃$S_3$. The quantum phases are determined by studying the excitations of these systems namely their fusion rules and the statistics. We then go further to construct a transfer matrix which contains the other Z₂${\mathbb{Z}}_2$ phase namely the double semion phase. More generally for other discrete groups these transfer matrices contain the twisted quantum double models. These transfer matrices can be thought of as being obtained by introducing extra parameters into the transfer matrix of lattice gauge theories. These parameters are central elements belonging to the tensor products of the algebra and its dual and are associated to vertices and volumes of the three dimensional lattice. As in the case of the lattice gauge theories we construct the operators creating the excitations in this case and study their braiding and fusion properties.     

Studies on the Solution Conformation and Dynamics of the Trisaccharide Repeating Unit of the Kps from Sinorhizobium Fredii Svq293

ABSTRACT

The conformational behaviour of the major trisaccharide repeating unit (α-D-Galp-(1→2)-β-D-Ribf-(1→9)-α-5-O-Me-Kdnp-) of the polysaccharide from Sinorhizobium fredii SVQ293, a mutant derivative has been analysed by NMR spectroscopy and extensive molecular dynamics simulations. The results obtained indicate that the five-membered ring adopts an almost unique conformation as do the pyranose rings. The Ribf-(1→9)-α-5-O-Me-Kdnp linkage may adopt a variety of conformations while the α-D-Galp-(1→2)-β-D-Ribf- also populates an extended surface of the Φ/Ψ map. Two 10 ns MD simulations using the GB/SA continuum solvent model for water and the MM3* force field provides a population distribution of conformers which satisfactorily agrees with the experimental NMR data for both the glycosidic linkages and the hydroxymethyl groups.     

Liquid—liquid coexistence curves for binary systems

The liquid—liquid coexistence curves of polar+non-polar binary systems have been determined experimentally. The polar compounds studied were ethanenitrile, methanol and N-methylpyrrolidone, whereas the non-polar compounds were chosen from the n-alkane series. The upper critical solution temperature for each set of mixtures increases with increasing n-alkane chain length, and the critical composition of the polar component also increases in this fashion.