Surface modification of mesoporous, macroporous, and amorphous silica with catalytically active polyoxometalate clusters

Transition-metal-substituted polyoxometalates (TMSP) of the type [MII(H2O)PW11O39]5- (M = Co, Zn) and [SiW9O37(CoII(H2O))3]10- have been chemically anchored to modified macroporous (400 nm pores), mesoporous (2.8 nm pores), and amorphous silica surfaces. The materials were characterized by solid-state 31P MAS NMR, UV-vis, FT-IR spectroscopy, and N2 adsorption experiments to verify cluster attachment and the structure of the TMSP on the support. On the basis of the spectroscopic evidence, clusters were attached datively to the surface, and the integrity of the [CoPW11] cluster was maintained for nonaqueous impregnation with TBA5[CoPW11]; partial degradation of the cluster occurred when it was impregnated from aqueous solution using the K5[CoPW11] salt. Both the amine surface groups and the cobalt centers in the clusters were found to be necessary to prevent cluster loss during washing or reaction processes. The catalytic activities of the supported TMSP clusters were tested by the epoxidation of cyclohexene to cyclohexene oxide in the presence of isobutyraldehyde. The percent conversion of the substrate and the amount of product formed per unit time were similar for [CoPW11] clusters on each of the three silica supports, but slightly lower than for purely homogeneous reactions. [SiW9Co3] clusters with three available cobalt centers exhibited higher catalytic activity with nearly identical performance on a silica support or in homogeneous solution.     

Potent and selective structure-based dibenzofuran inhibitors of transthyretin amyloidogenesis: kinetic stabilization of the native state

Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation and partial monomer denaturation to produce a misassembly competent species. This process has been followed by turbidity to identify transthyretin amyloidogenesis inhibitors including dibenzofuran-4,6-dicarboxylic acid (1). An X-ray cocrystal structure of TTR.1(2) reveals that it only utilizes the outer portion of the two thyroxine binding pockets to bind to and inhibit TTR amyloidogenesis. Herein, structure-based design was employed to append aryl substituents at C1 of the dibenzofuran ring to complement the unused inner portion of the thyroxine binding pockets. Twenty-eight amyloidogenesis inhibitors of increased potency and dramatically increased plasma TTR binding selectivity resulted. These function by imposing kinetic stabilization on the native tetrameric structure of TTR, creating a barrier that is insurmountable under physiological conditions. Since kinetic stabilization of the TTR native state by interallelic trans suppression is known to ameliorate disease, there is reason to be optimistic that the dibenzofuran-based inhibitors will do the same. Preventing the onset of amyloidogenesis is the most conservative strategy to intervene clinically, as it remains unclear which of the TTR misassembly intermediates results in toxicity. The exceptional binding selectivity enables these inhibitors to occupy the thyroxine binding site(s) in a complex biological fluid such as blood plasma, required for inhibition of amyloidogenesis in humans. It is now established that the dibenzofuran-based amyloidogenesis inhibitors have high selectivity, affinity, and efficacy and are thus excellent candidates for further pharmacologic evaluation.     

GlyNet: a multi-task neural network for predicting protein–glycan interactions

Advances in diagnostics, therapeutics, vaccines, transfusion, and organ transplantation build on a fundamental understanding of glycan–protein interactions. To aid this, we developed GlyNet, a model that accurately predicts interactions (relative binding strengths) between mammalian glycans and 352 glycan-binding proteins, many at multiple concentrations. For each glycan input, our model produces 1257 outputs, each representing the relative interaction strength between the input glycan and a particular protein sample. GlyNet learns these continuous values using relative fluorescence units (RFUs) measured on 599 glycans in the Consortium for Functional Glycomics glycan arrays and extrapolates these to RFUs from additional, untested glycans. GlyNet''s output of continuous values provides more detailed results than the standard binary classification models. After incorporating a simple threshold to transform such continuous outputs the resulting GlyNet classifier outperforms those standard classifiers. GlyNet is the first multi-output regression model for predicting protein–glycan interactions and serves as an important benchmark, facilitating development of quantitative computational glycobiology.

GlyNet, a neural net model of glycan-protein binding strengths. Given a glycan it outputs binding to each of several protein samples. Reproducing glycan array data, it extrapolates the binding of untested glycans against the protein samples.     

ELECTRON-TRANSFER PROCESSES. PART 40. REACTION OF ALKYL RADICALS WITH DIPHENYLPHOSPHIDE ANION

Abstract

The anion Ph₂P^? (K⁺, 18-crown-6) reacts with t-BuHgCl in HMPA to form Ph₂PCMe₃ by a free radical chain mechanism. In Me₂SO, Ph₂P(O)CMe₃ is produced. Reaction of Ph₂P^? with PhCOCH₂HgCl yields the oxidative dimerization product isolable from HMPA but readily converted to Ph₂P(O)P(O)Ph₂ in Me₂SO.     

Single‐pulse pulsed laser polymerization–electron paramagnetic resonance investigations into the termination kinetics of n‐butyl acrylate macromonomers

The termination of model mid‐chain radicals (MCRs), which mimic radicals that occur in acrylate polymerization over a broad range of reaction conditions, has been studied by single‐pulse pulsed laser polymerization (SP‐PLP) in conjunction with electron paramagnetic resonance spectroscopy. The model radicals were generated by initiator‐fragment addition to acrylic macromonomers that were preformed prior to the kinetic experiments, thus enabling separation of termination from the propagation reaction, for these model radicals propagate sparingly, if at all, on the timescale of SP‐PLP experiments. Termination rate coefficients of the MCRs were determined in the temperature range of 0–60°C in acetonitrile and butyl propionate solution as well as in bulk macromonomer over the range of 0–100 °C. Termination rate coefficients slightly below those of the corresponding secondary radicals were deduced, demonstrating the relatively high termination activity of this species, even when undergoing MCR–MCR termination. For chain length of 10, a reduction by a factor of 6 is observed. Unusually high activation energies were found for the termination rate coefficient in these systems, with 35 kJ mol^?1 being determined for bulk macromonomer. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Characterization and Control of Residual Stress and Curvature in Anodically Bonded Devices and Substrates with Etched Features

While anodic bonding is commonly used in a variety of microelectromechanical systems (MEMS) applications, devices and substrates that incorporate this processing technique are often subjected to significant residual stress and curvature that create post-processing and reliability issues. Here, using an anisothermal anodic bonding procedure, residual stresses and the resulting wafer curvature in these structures are controlled by varying the initial bond temperatures of the silicon and Pyrex wafers independently. Residual stresses are quantified by measuring bulk wafer curvature and, locally, stress concentrations are measured using infrared photoelasticity accompanied by 3-D thermomechanical finite element analysis. Based on the good agreement between numerical predictions and experimental results, this process can be used to determine the bulk post-bond wafer curvature and to reduce the likelihood of structural failure at these sites, by changing the residual stresses from tensile in nature, which may drive initiation and growth of cracks, to compressive, which can suppress such failures.     

Synthesis and characterization of ultrafine lithium ferrite from a citrate precursor

Ultrafine particles of lithium ferrite have been prepared at the unusually low temperatures of 240 and 455°C by a citrate precursor method. The materials obtained after annealing at temperatures between 455 and 700°C consist of ordered lithium ferrite as shown by the characteristics infrared absorptions, the X-ray diffraction superstructure reflections, and the 4.2 K Mössbauer spectra. The values of magnetization obtained are somewhat low, due to the presence of small quantities of an -Fe₂O₃ phase, which can also be observed in the X-ray diffraction and the Mössbauer spectra.