Noviose mimics of the coumarin inhibitors of gyrase B

The design, synthesis, and biological activity in vitro of modified coumarin inhibitors of gyrase B are presented. Noviose, the sugar portion of coumarin antibiotics, was replaced by simplified mimics, a 5′,5′-dimethylcyclohexane or piperidine.     

Theoretical investigation of the isomerization of trans-HCOH to H2CO: an example of a water-catalyzed reaction

A concerted hydrogen atom transfer mechanism has been elucidated for the isomerization of trans-HCOH to H(2)CO using a variety of ab initio and density functional theory methods. This work places specific emphasis on the role water molecules can play as a catalyst for this reaction and the mechanism by which this is achieved. This is of particular importance in the context of molecular ices in the interstellar medium because the presence of water in this reaction reduces the activation energy by at least 80%, which is accompanied by a significant enhancement of the reaction rate, at ≤300 K.     

Sweet (hetero)aromatics: glycosylated templates for the construction of saccharide mimetics

Mono- and diglycosylated aromatics and heteroaromatics may serve as building blocks for the construction of metabolically stable mimetics of oligosaccharides. Methods for their preparation from monosaccharidic precursors by direct C-glycosylation, dipolar cycloaddition or Larock cyclization are described.     

Study of flammability and thermal properties of high-impact polystyrene nanocomposites

To increase thermal stability and flammability of high-impact polystyrene (HIPS) nanocomposites with silica nanoparticles and two types of polyphosphate flame retardants were prepared by extrusion. Nanocomposites were characterized by thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, limiting oxygen index (LOI) analysis and the evaluation of mechanical properties. It was found that organic polyphosphate in combination with silica increased thermal stability and fire retardancy by 50% in LOI test. Morphology characterization revealed existence of crystalline order which affected mechanical properties; tensile strength was approximately the same as virgin HIPS while elasticity was sharply decreased. Ammonium polyphosphate did not affect mechanical properties as much as the organic material but was not equally efficient in flame retardancy which was just marginally increased.     

3D-structure of cycloreticulin C and glabrin A, cyclopeptides from the seeds of Annona reticulata

Two cyclopeptides, the cycloheptapeptide cycloreticulin C, cyclo(Pro¹-Gly²-Gln³-Pro⁴-Pro⁵-Tyr⁶-Val⁷) (1), and the cyclohexapeptide glabrin A, cyclo(Pro¹-Gly²-Leu³-Val⁴-Ile⁵-Tyr⁶) (2), have been isolated from the methanol extract of the seeds of Annona reticulata. Their structures were elucidated on the basis of the MS/MS fragmentation using a Q-TOF mass spectrometer equipped with an ESI source, chemical degradation and extensive 2D-NMR. The solution conformation of cycloreticulin C involves two β-turns, one of type II with trans-Pro¹ and Gly² at the corners, another of type VIa with trans-Pro⁴ and cis-Pro⁵ at the corners, and followed by a β-bulge at the Tyr⁶-Val⁷ level. The solid state and solution conformations of glabrin A have been analyzed by X-ray and 2D-NMR studies, respectively, and are characterized by the presence of two β-turns, the first of type VIa and the second intermediary between types I and III at the solid state and a γ-turn in solution.     

Intraventricular thrombus formation in the LVAD-assisted heart studied in a mock circulatory loop

Left ventricular assist devices (LVADs) are mechanical pumps that are surgically attached to the left ventricle and aorta. Clinical studies show that LVADs improve patient health and quality of life, and dramatically reduce the mortality of cardiac failure. During periods of high LVAD support, blood flow occurs entirely through the LVAD, the aortic valve is continuously closed, and the heart operates in series with the pump. Thus the normal fluid dynamics of intraventricular flow are altered and linked to the development of thrombus in both the native heart and LVAD. Our goal in this study was to simulate a patient with a recurring thrombus and quantify the variations in the flow field in the LV as the thrombus developed. Particle image velocimetry measurements of transparent silicone models were performed for a range of LVAD support conditions. Results show that the presence of a small thrombus in the LVOT creates a favorable condition for further growth, especially in the presence of high LVAD support. As the thrombus enlarges, it begins to affect the normal vortex-flow pattern, further reducing flow rate and pulsatility in the LVOT. Evaluation of vortex dynamics and stasis regions in both patients and experimental models of LVAD support yield quantitative metrics that can be used to assess the risk of thrombus and the development of strategies to reduce this risk in LVAD patients.     

From exponential to linear growth in polyelectrolyte multilayers

There exist two types of polyelectrolyte multilayers: those whose thickness increases linearly with the number of deposition steps, which are nicely structured, and those whose thickness increases exponentially, which resembles hydrogels. This simple picture has recently slightly evolved with the finding that some exponentially growing films enter into a linear growth phase after a certain number of deposition steps. In this study, we investigate the buildup process of hyaluronic acid/poly(L-lysine) (HA/PLL) multilayers that constitute one of the best known exponentially growing systems. The films are built by using two deposition methods: the well-known dipping method and the more recent spraying method where the polyelectrolyte solutions are sprayed alternately onto a vertical substrate. The goal of this study is twofold. First, we investigate the influence of the main parameters (i.e., spraying rate and spraying time) of the spraying method on the film growth process. We find that, as for the dipping method, the film thickness first evolves exponentially with the number of deposition steps, and after a given number of deposition steps, it follows a linear evolution. We find that similar behavior is observed with the dipping method. Second, because the spraying method allows the very fine variation of the different parameters of the buildup, we use this method to investigate the exponential-to-linear transition. We find that this transition always takes place after about 12 deposition steps whatever the values of the parameters controlling the deposition process. We discuss our results in light of a model proposed by Hübsch et al. (Hübsch, E.; Ball, V.; Senger, B.; Decher, G.; Voegel, J. C.; Schaaf, P. Langmuir 2004, 20, 1980-1985) and later by Salom?ki et al. (Salom?ki, M.; Vinokurov, I. A.; Kankare, J. Langmuir 2005, 21, 11232-11240) in which it is assumed that the exponential-to-linear transition is due to a film restructuring that progressively forbids the diffusion of one of the polyelectrolytes constituting the film over part of the film. This "forbidden" zone then grows with the number of deposition steps so that the outer zone of the film that is still concerned with diffusion keeps a constant thickness and moves upward as the total film thickness increases.     

Effects of dipolar interactions on linear and nonlinear optical properties of multichromophore assemblies: a case study

Interchromophore interactions in flexible multidipolar structures for nonlinear optics were addressed by a combined experimental and theoretical study on two series of one-, two-, and three-chromophore systems in which identical push-pull chromophores are assembled through covalent and flexible linkers in close proximity. The photophysical and nonlinear optical properties (quadratic hyperpolarizability) of the multichromophore systems were investigated and compared to those of the monomeric chromophores. Multimers have larger dipole moments than their monomeric analogues, that is, the dipolar subchromophores self-orientate within the multimeric structures. This effect was found to depend on the intersubchromophore distance in a nontrivial manner, which confirms that molecular engineering of such flexible systems is more complex than in completely geometrically controlled systems. Electric-field-induced second-harmonic generation (EFISHG) measurements in solution revealed increased figures of merit as compared to the monomeric analogue. This effect increases with increasing number and polarity of the individual subchromophores in the nanoassembly and increasing spacing between dipolar subchromophores. Experimental results are interpreted by a theoretical model for interacting polar and polarizable chromophores. The properties of multidipolar assemblies are shown to be related to the relative orientation of chromophores, which is imposed by interchromophore interactions. The supramolecular structure is thus a result of self-organization. The proposed theoretical model was also used to predict the properties of multichromophore structures made up of more polar and polarizable push-pull chromophores, and showed that stronger interchromophore interactions can heavily affect the individual optical responses. This suggests new routes for engineering highly NLO responsive multichromophore systems.     

ε-Aminocaproylcholine: Chemical Synthesis,Biological Properties,and Interactions with Receptor Molecules

ε-Aminocaproylcholine, [¹⁴CH₃-]ε-aminocaproylcholine, and their Sepharose-2B derivatives ( 6 ) were synthesized. ε-Aminocaproylcholine is a full cholinergic agonist (nicotinic) with a potency intermediate between that of acetylcholine and of carbachol. ε-Aminocaproylcholine is not hydrolysed by acetylcholine esterase, but is an inhibitor. Its Sepharose-2B derivatives are shown to be effective affinity-chromatographic agents for the isolation of acetylcholine-binding proteins (receptors).     

Stereochemistry-59: New insights into the mechanism of the proline-catalyzed asymmetric robinson cyclization; structure of two intermediates. asymmetric dehydration

Two sets of results give information about the mechanism of carbonyl activation by (S)-proline during asymmetric syntheses: (i) X-ray structures of two ketols produced by the proline-induced cyclization of triketones; (ii) (S)-Proline-catalyzed asymmetric dehydration of (±)-β ketols leading to optically active enones.