Raman Spectroscopy-Based Assessment of the Liquid Water Content in Snow

In snow, water coexists in solid, liquid and vapor states. The relative abundance of the three phases drives snow grain metamorphism and affects the physical properties of the snowpack. Knowledge of the content of the liquid phase in snow is critical to estimate the snowmelt runoff and to forecast the release of wet avalanches. Liquid water does not spread homogeneously through a snowpack because different snow layers have different permeabilities; therefore, it is important to track sudden changes in the amount of liquid water within a specific layer. We reproduced water percolation in the laboratory, and used Raman spectroscopy to detect the presence of the liquid phase in controlled snow samples. We performed experiments on both fine- and coarse-grained snow. The obtained snow spectra are well fitted by a linear combination of the spectra typical of liquid water and ice. We progressively charged snow with liquid water from dry snow up to soaked snow. As a result, we exploited continuous, qualitative monitoring of the evolution of the liquid water content as reflected by the fitting coefficient c.     

Synthetic studies toward bicyclic endoperoxides presenting polar side chains

We developed a synthetic strategy for the preparation of tetrahydrofuro[2,3-c][1,2]dioxane and 2,3,8-trioxa[3,3,1]nonanes bearing polar functional groups at C3 and C4, respectively. The synthetic strategy has been applied to the synthesis of 2,3,8-trioxa[3,3,1]nonanes bearing various amides and amines at C3 useful for structure-activity relationships investigation as antiplasmodial compounds. The synthesis of 1 and the reaction conditions identified for its conversion to amides and amines could pose the basis for the use of this class of endoperoxides also in conjugation with other drugs for polypharmacology approaches.     

A Concise and Highly Enantioselective Total Synthesis of (+)‐anti‐ and (−)‐syn‐Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the Mefloquines

A concise asymmetric (>99:1 e.r.) total synthesis of (+)‐anti‐ and (?)‐syn‐mefloquine hydrochloride from a common intermediate is described. The key asymmetric transformation is a Sharpless dihydroxylation of an olefin that is accessed in three steps from commercially available materials. The Sharpless‐derived diol is converted into either a trans or cis epoxide, and these are subsequently converted into (+)‐anti‐ and (?)‐syn‐mefloquine, respectively. The synthetic (+)‐anti‐ and (?)‐syn‐mefloquine samples were derivatized with (S)‐(+)‐mandelic acid tert‐butyldimethylsilyl ether, and a crystal structure of each derivative was obtained. These are the first X‐ray structures for mefloquine derivatives that were obtained by coupling to a known chiral, nonracemic compound, and provide definitive confirmation of the absolute stereochemistry of (+)‐anti‐ as well as (?)‐syn‐mefloquine.     

Receptor‐Bound Conformation of Cilengitide Better Represented by Its Solution‐State Structure than the Solid‐State Structure

The X‐ray crystal and NMR spectroscopic structures of the peptide drug candidate Cilengitide (cyclo(RGDf(NMe)Val)) in various solvents are obtained and compared in addition to the integrin receptor bound conformation. The NMR‐based solution structures exhibit conformations closely resembling the X‐ray structure of Cilengitide bound to the head group of integrin αvβ3. In contrast, the structure of pure Cilengitide recrystallized from methanol reveals a different conformation controlled by the lattice forces of the crystal packing. Molecular modeling studies of the various ligand structures docked to the αvβ3 integrin revealed that utilization of the solid‐state conformation of Cilengitide leads—unlike the solution‐based structures—to a mismatch of the ligand–receptor interactions compared with the experimentally determined structure of the protein–ligand complex. Such discrepancies between solution and crystal conformations of ligands can be misleading during the structure‐based lead optimization process and should thus be taken carefully into account in ligand orientated drug design.     

Breaking the Dogma of the Metal‐Coordinating Carboxylate Group in Integrin Ligands: Introducing Hydroxamic Acids to the MIDAS To Tune Potency and Selectivity

A suitable substitute : All integrin receptors bind their ligands, which contain an aspartate residue, in the metal‐ion‐ dependent adhesion site (MIDAS). So far all attempts to replace the carboxyl group of aspartate with other, pharmacologically favorable isosteric groups have failed. Now it has been shown that a hydroxamic acid group can replace the carboxyl group; the resulting ligand retains its high binding activity. The picture shows one such ligand in the binding site of αvβ3.

     

Cover Picture: Breaking the Dogma of the Metal‐Coordinating Carboxylate Group in Integrin Ligands: Introducing Hydroxamic Acids to the MIDAS To Tune Potency and Selectivity (Angew. Chem. Int. Ed. 24/2009)

The binding of the carboxyl group of an aspartate residue in the metal‐ion‐dependent adhesion site (MIDAS) is a key feature in the binding of ligands to integrins. This finding was demonstrated by the binding of the cyclic pentapeptide cyclo(RGDfNMeV) (Cilengitid) to the integrin αvβ3 (see picture). In their Communication on p. 4436 ff, H. Kessler and co‐workers show that the carboxyl group previously considered essential for binding can be replaced by a hydroxamic acid unit.

     

Solid-state structure and conformation of (Z)-2-(phenylbenzylidene)-3-quinuclidinone,an intermediate in the synthesis of quinuclidine derivatives

(Z)-2-(2-phenylbenzylidene)-3-quinuclidinone, C₂₀H₁₉NO,M _r =300.47D crystallizes in the monoclinicP2₁/c space group witha = 6.9809(2) Å,b=19.0523(2) Å,c = 11.7733(1) Å,=100.92(2)°,V=1537.5(3) ų,Z=4,D _c = 1.298 g/cm³,D _x =1.29 g/cm³ (flotation). Diffractometric data, using CuK radiation,=1.54178 Å, were collected on plate-like crystals. The structure, solved by direct methods was refined to a final R value of 0.037 for the 2645 observed reflections withF _o >3.0(F _o ). The molecule shows a trans conformation around the double bond. The quinuclidine and the diphenyl moieties present deformations in their geometric and conformational parameters due to the need of releasing intramolecular strains and/or nonbonded interactions.     

The effect of solvent on the morphology of ZnO nanostructure assembly by dielectrophoresis and its device applications

Different zinc oxide nanostructured morphologies were grown on photolithographically patterned silicon/silicon dioxide substrates by dielectrophoresis technique using different solvents, such as water and ethanol, obtaining rod-like and net-like nanostructures, respectively. The formation of continuous nanostructures was confirmed by scanning electron microscopic, atomic force microscopic images, and electrical characterizations. The rod-like zinc oxide nanostructures were observed in the 10 μm gap between the fingers in the pattern, whereas net-like nanostructures were formed independently of microgap. A qualitative study about the mechanism for the assembly of zinc oxide continuous nanostructures was presented. Devices were electrically characterized, at room temperature, in controlled environment to measure the conductance behavior in ultraviolet and humidity environment. Devices based on zinc oxide nanostructures grown in ethanol medium show better responses under both ultraviolet and humidity, because of the net-like structure with high surface-to-volume ratio.