Engineering the Biosynthesis of the Polyketide-Nonribosomal Peptide Collismycin A for Generation of Analogs with Neuroprotective Activity

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Single‐Particle Spectroscopy on Large SAPO‐34 Crystals at Work: Methanol‐to‐Olefin versus Ethanol‐to‐Olefin Processes

The formation of hydrocarbon pool (HCP) species during methanol‐to‐olefin (MTO) and ethanol‐to‐olefin (ETO) processes have been studied on individual micron‐sized SAPO‐34 crystals with a combination of in situ UV/Vis, confocal fluorescence, and synchrotron‐based IR microspectroscopic techniques. With in situ UV/Vis microspectroscopy, the intensity changes of the λ=400 nm absorption band, ascribed to polyalkylated benzene (PAB) carbocations, have been monitored and fitted with a first‐order kinetics at low reaction temperatures. The calculated activation energy (E_a) for MTO, approximately 98 kJ mol^?1, shows a strong correlation with the theoretical values for the methylation of aromatics. This provides evidence that methylation reactions are the rate‐determining steps for the formation of PAB. In contrast for ETO, the E_a value is approximately 60 kJ mol^?1, which is comparable to the E_a values for the condensation of light olefins into aromatics. Confocal fluorescence microscopy demonstrates that during MTO the formation of the initial HCP species are concentrated in the outer rim of the SAPO‐34 crystal when the reaction temperature is at 600 K or lower, whereas larger HCP species are gradually formed inwards the crystal at higher temperatures. In the case of ETO, the observed egg‐white distribution of HCP at 509 K suggests that the ETO process is kinetically controlled, whereas the square‐shaped HCP distribution at 650 K is indicative of a diffusion‐controlled process. Finally, synchrotron‐based IR microspectroscopy revealed a higher degree of alkylation for aromatics for MTO as compared to ETO, whereas high reaction temperatures favor dealkylation processes for both the MTO and ETO processes.     

Synthesis,Biological Evaluation,WAC and NMR Studies of S‐Galactosides and Non‐Carbohydrate Ligands of Cholera Toxin Based on Polyhydroxyalkylfuroate Moieties

The synthesis of several non‐carbohydrate ligands of cholera toxin based on polyhydroxyalkylfuroate moieties is reported. Some of them have been linked to D ‐galactose through a stable and well‐tolerated S‐glycosidic bond. They represent a novel type of non‐hydrolyzable bidentate ligand featuring galactose and polyhydroxyalkylfuroic esters as pharmacophoric residues, thus mimicking the GM1 ganglioside. The affinity of the new compounds towards cholera toxin was measured by weak affinity chromatography (WAC). The interaction of the best candidates with this toxin was also studied by saturation transfer difference NMR experiments, which allowed identification of the binding epitopes of the ligands interacting with the protein. Interestingly, the highest affinity was shown by non‐carbohydrate mimics based on a polyhydroxyalkylfuroic ester structure.     

Mechanistic Studies on the Rearrangement of 1‐Alkenyl‐2‐alkynylcyclopropanes: From Allylic Gold(I) Cations to Stable Carbocations

An allylic gold(I) cation, proposed as key intermediate in the gold‐promoted rearrangement of 1,5‐enynes bearing a fixed conformation, has been detected and characterized by NMR spectroscopy. Moreover, its participation in the overall transformation was confirmed. Computational studies indicate that the gold‐catalyzed transformation occurs through an uncommon rearrangement. Additionally, this study led us to isolate and characterize a stable homoantiaromatic carbocation.     

Complex salts of [ReII(NO)Br4(pyz)]−: synthesis,crystal structures,and DFT studies

Two nitrosyl Re(II) complexes formulated as [Ni(bipy)₃][Re(NO)Br₄(pyz)]₂ and [Cu(bipy)₂Br][ReNOBr₄(pyz)] (pyz = pyrazine, bipy = 2,2′-bipyridine) were synthesized and characterized by single-crystal X-ray diffraction. The pyrazine in [Re(NO)Br₄(pyz)]^? was not able to act as bridge toward a second metal ion, and the two salts were obtained. Computational studies at the density functional level of theory show that the charge on the nitrogen, which could be available for bridging, is dramatically reduced to less than half, decreasing its capability to bind a second metal ion.     

Evaluation of fritless solid‐phase extraction coupled on‐line with capillary electrophoresis‐mass spectrometry for the analysis of opioid peptides in cerebrospinal fluid

Fritless SPE on‐line coupled to CE with UV and MS detection (SPE‐CE‐UV and SPE‐CE‐MS) was evaluated for the analysis of opioid peptides. A microcartridge of 150 μm id was packed with a C₁₈ sorbent (particle size > 50 μm), which was retained between a short inlet capillary and a separation capillary (50 μm id). Several experimental parameters were optimized by SPE‐CE‐UV using solutions of dynorphin A (DynA), endomorphin 1 (End1), and methionine‐enkephaline (Met). A microcartridge length of 4 mm was selected, sample was loaded for 10 min at 930 mbar and the retained peptides were eluted with 67 nL of an acidic hydro‐organic solution. Using SPE‐CE‐MS, peak area and migration time repeatabilities for the three opioid peptides were 12–27% and 4–5%, respectively. SPE recovery was lower for the less hydrophobic DynA (22%) than for End1 (66%) and Met (78%) and linearity was satisfactory in all cases between 5 and 60 ng/mL. The LODs varied between 0.5 and 1.0 ng/mL which represent an enhancement of two orders of magnitude when compared with CE‐MS. Cerebrospinal fluid (CSF) samples spiked with the opioid peptides were analyzed to demonstrate the applicability to biological samples. Peak area and migration time repeatabilities were similar to the standard solutions and the opioid peptides could be detected down to 1.0 ng/mL.     

The Limitations of Nonlinear Fluorescence Effect in Super Resolution Saturated Structured Illumination Microscopy System

Classically, optical systems are considered to have a fundamental resolution limit due to diffraction. Many strategies for improving both axial and lateral resolutions are based on a priori information about the input signal. These strategies lead to a numerical aperture improvement. However these are still limited by the wave nature of light. By using fluorescence technique one theoretically can reach unlimited resolution. The key point is to use the nonlinear dependence of the fluorescence emission rate on the intensity of the applied illumination. In this paper we present simulation as well as experimental results which show the advantage and the problems of using the nonlinear fluorescence effect in super resolution systems as well as discussing the nonlinear phenomena concerning the fluorescence process. The results show that the nonlinear fluorescence effect is accompanied by severe quenching, bleaching and saturation phenomena. As consequence, super resolution using saturated structured illumination method in living biological samples becomes severely restricted.     

Spectral response and far-field pattern of a dipole nano-antenna on metamaterial substrates having near-zero and negative indices of refraction

In this work the resonance, frequency response, and far-field patterns of an optical nano-antenna placed on an interface between air and a metamaterial substrate is obtained through finite element calculations. The metamaterial is characterized by an effective, macroscopic index of refraction which can take negative and near-zero values, or by published values of the effective permittivity and permeability for metamaterials. The results show that the resonant wavelength and response can be fitted to analytical functions that are even functions of the index of refraction, this is consistent with the knowledge that negative indices of refraction allows for wave propagation in the same magnitude but opposite direction observed with positive indices of refraction. The simulations also show that substrates with near-zero index of refraction will enhance the antenna response by 62% compared to substrates with n > 1. Lossy metamaterials are also considered in the simulations. The far-field pattern of the antenna, obtained through a near-field to far-field transformation, behaves the same independently of the sign of the index of refraction, also the far-field pattern for the emission towards near-zero substrates is nearly constant and independent of the angle for the evaluated angular range.