The Structure of Liquid and Glassy Carbamazepine.

To enhance the solubility of orally administered pharmaceuticals, liquid capsules or amorphous tablets are often preferred over crystalline drug products. However, little is known regarding the variation in bonding mechanisms between pharmaceutical molecules in their different disordered forms. In this study, liquid and melt-quenched glassy carbamazepine have been studied using high energy X-ray diffraction and modeled using Empirical Potential Structure Refinement.

Evidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing.

Sensing and responding to temperature is crucial in biology. The TRPV1 ion channel is a well-studied heat-sensing receptor that is also activated by vanilloid compounds, including capsaicin. Despite significant interest, the molecular underpinnings of thermosensing have remained elusive.

Development of a Fragment-Based Screening Assay for the Focal Adhesion Targeting Domain Using SPR and NMR.

The Focal Adhesion Targeting (FAT) domain of Focal Adhesion Kinase (FAK) is a promising drug target since FAK is overexpressed in many malignancies and promotes cancer cell metastasis. The FAT domain serves as a scaffolding protein, and its interaction with the protein paxillin localizes FAK to focal adhesions. Various studies have highlighted the importance of FAT-paxillin binding in tumor growth, cell invasion, and metastasis.

Hierarchical spidroin micellar nanoparticles as the fundamental precursors of spider silks.

Many natural silks produced by spiders and insects are unique materials in their exceptional toughness and tensile strength, while being lightweight and biodegradable-properties that are currently unparalleled in synthetic materials. Myriad approaches have been attempted to prepare artificial silks from recombinant spider silk spidroins but have each failed to achieve the advantageous properties of the natural material. This is because of an incomplete understanding of the in vivo spidroin-to-fiber spinning process and, particularly, because of a lack of knowledge of the true morphological nature of spidroin nanostructures in the precursor dope solution and the mechanisms by which these nanostructures transform into micrometer-scale silk fibers.

Concerted One-Electron Two-Proton Transfer Processes in Models Inspired by the Tyr-His Couple of Photosystem II.

Nature employs a Tyr-His pair as a redox relay that couples proton transfer to the redox process between P680 and the water oxidizing catalyst in photosystem II. Artificial redox relays composed of different benzimidazole-phenol dyads (benzimidazole models His and phenol models Tyr) with substituents designed to simulate the hydrogen bond network surrounding the Tyr-His pair have been prepared. When the benzimidazole substituents are strong proton acceptors such as primary or tertiary amines, theory predicts that a concerted two proton transfer process associated with the electrochemical oxidation of the phenol will take place.

Secondary Structure Adopted by the Gly-Gly-X Repetitive Regions of Dragline Spider Silk.

Solid-state NMR and molecular dynamics (MD) simulations are presented to help elucidate the molecular secondary structure of poly(Gly-Gly-X), which is one of the most common structural repetitive motifs found in orb-weaving dragline spider silk proteins. The combination of NMR and computational experiments provides insight into the molecular secondary structure of poly(Gly-Gly-X) segments and provides further support that these regions are disordered and primarily non-β-sheet. Furthermore, the combination of NMR and MD simulations illustrate the possibility for several secondary structural elements in the poly(Gly-Gly-X) regions of dragline silks, including β-turns, 3-helicies, and coil structures with a negligible population of α-helix observed.

Microscale Mechanism of Age Dependent Wetting Properties of Prickly Pear Cacti (Opuntia).

Cacti thrive in xeric environments through specialized water storage and collection tactics such as a shallow, widespread root system that maximizes rainwater absorption and spines adapted for fog droplet collection. However, in many cacti, the epidermis, not the spines, dominates the exterior surface area. Yet, little attention has been dedicated to studying interactions of the cactus epidermis with water drops.

Isolation of a bis(imino)pyridine molybdenum(i) iodide complex through controlled reduction and interconversion of its reaction products.

Analysis of previously reported [((Ph2PPr)PDI)MoI][I] by cyclic voltammetry revealed a reversible wave at -1.20 V vs. Fc(+/0), corresponding to the Mo(ii)/Mo(i) redox couple.

NMR Structure of Francisella tularensis Virulence Determinant Reveals Structural Homology to Bet v1 Allergen Proteins.

Tularemia is a potentially fatal bacterial infection caused by Francisella tularensis, and is endemic to North America and many parts of northern Europe and Asia. The outer membrane lipoprotein, Flpp3, has been identified as a virulence determinant as well as a potential subunit template for vaccine development. Here we present the first structure for the soluble domain of Flpp3 from the highly infectious Type A SCHU S4 strain, derived through high-resolution solution nuclear magnetic resonance (NMR) spectroscopy; the first structure of a lipoprotein from the genus Francisella.

Multiporphyrin arrays with π-π interchromophore interactions.

A recently reported synthetic method has been employed to prepare several arrays of free base and zinc porphyrins. In the arrays, the porphyrins are arranged around a central benzene ring. The lack of aryl rings in the linkages to the central benzene ring, coupled with the presence of only one meso-aryl substituent on each porphyrin, allows strong electronic interactions between the porphyrin macrocycles.

Modulating short wavelength fluorescence with long wavelength light.

Two molecules in which the intensity of shorter-wavelength fluorescence from a strong fluorophore is modulated by longer-wavelength irradiation of an attached merocyanine-spirooxazine reverse photochromic moiety have been synthesized and studied. This unusual fluorescence behavior is the result of quenching of fluorophore fluorescence by the thermally stable, open, zwitterionic form of the spirooxazine, whereas the photogenerated closed, spirocyclic form has no effect on the fluorophore excited state. The population ratio of the closed and open forms of the spirooxazine is controlled by the intensity of the longer-wavelength modulated light.

High-resolution NMR reveals secondary structure and folding of amino acid transporter from outer chloroplast membrane.

Solving high-resolution structures for membrane proteins continues to be a daunting challenge in the structural biology community. In this study we report our high-resolution NMR results for a transmembrane protein, outer envelope protein of molar mass 16 kDa (OEP16), an amino acid transporter from the outer membrane of chloroplasts. Three-dimensional, high-resolution NMR experiments on the (13)C, (15)N, (2)H-triply-labeled protein were used to assign protein backbone resonances and to obtain secondary structure information.

Structural characterization and aging of glassy pharmaceuticals made using acoustic levitation.

Here, we report the structural characterization of several amorphous drugs made using the method of quenching molten droplets suspended in an acoustic levitator. (13) C NMR, X-ray, and neutron diffraction results are discussed for glassy cinnarizine, carbamazepine, miconazole nitrate, probucol, and clotrimazole. The (13) C NMR results did not find any change in chemical bonding induced by the amorphization process.

Oxidative coupling of porphyrins using copper(II) salts.

A method for radical coupling of porphyrins using copper(II) salts as one-electron oxidants was developed. A Zn(II)-porphyrin bearing an aminophenyl group yielded porphyrin oligomers, and two tri-arylporphyrins were oxidized to form doubly and triply linked dimers. Bromination of doubly linked dimers gave macrocycles with twisted skeletons.

Measuring glomerular number and size in perfused kidneys using MRI.

The goal of this work was to nondestructively measure glomerular (and thereby nephron) number in the whole kidney. Variations in the number and size of glomeruli have been linked to many renal and systemic diseases. Here, we develop a robust magnetic resonance imaging (MRI) technique based on injection of cationic ferritin (CF) to produce an accurate measurement of number and size of individual glomeruli.

Proton-detected heteronuclear single quantum correlation NMR spectroscopy in rigid solids with ultra-fast MAS.

In this article, we show the potential for utilizing proton-detected heteronuclear single quantum correlation (HSQC) NMR in rigid solids under ultra-fast magic angle spinning (MAS) conditions. The indirect detection of carbon-13 from coupled neighboring hydrogen nuclei provides a sensitivity enhancement of 3- to 4-fold in crystalline amino acids over direct-detected versions. Furthermore, the sensitivity enhancement is shown to be significantly larger for disordered solids that display inhomogeneously broadened carbon-13 spectra.

ClnH6-nSiGe compounds for CMOS compatible semiconductor applications: synthesis and fundamental studies.

We describe the synthesis of a new family of chlorinated Si-Ge hydrides based on the formula ClnH6-nSiGe. Selectively controlled chlorination of H3SiGeH3 is provided by reactions with BCl3 to produce ClH2SiGeH3 (1) and Cl2HSiGeH3 (2). This represents a viable single-step route to the target compounds in commercial yields for semiconductor applications.

Tribasic lead maleate and lead maleate: synthesis and structural and spectroscopic characterizations.

We report on the synthesis and structure of tribasic lead maleate hemihydrate ([Pb4O3]C2H2(CO2)2.(1/2)H2O, TRIMAL) and lead maleate (PbC2H2(CO2)2, PBMAL). The structure of [Pb4O3]C2H2(CO2)2.

Multinuclear NMR investigations of the oxygen, water, and hydroxyl environments in sodium hexaniobate.

Solid-state (1)H, (17)O MAS NMR, (1)H-(93)Nb TRAPDOR NMR, and (1)H double quantum 2D MAS NMR experiments were used to characterize the oxygen, water, and hydroxyl environments in the monoprotonated hexaniobate material, Na(7)[HNb(6)O(19)].15H(2)O. These solid-state NMR experiments demonstrate that the proton is located on the bridging oxygen of the [Nb(6)O(19)](8-) cluster.

A general synthetic procedure for heteropolyniobates.

The heteropolyanions of W, Mo, and V, which have found numerous applications, are formed simply by acidification of solutions of their oxoanions. Under similar conditions, these oxoanion precursors are not available for Nb, and Nb-oxo chemistry is dominated by formation of the Lindquist ion [Nb6O19]8- only. However, heteropolyniobate formation is favored in hydrothermal reactions of aqueous, alkaline precursor mixtures.