Systematische untersuchungen über das verhalten von organozinnverbindungen gegenüber flüssigem schwefeldioxid II. Reaktionen von arylstannanen mit flüssigem SO2

The behaviour of tetraarylstannanes, R₄Sn (R = C₆H₅CH₂, C₆H₅, o-, m-, p-CH₃C₆H₄), towards SO₂ under various conditions has now been studied in detail. Compared to aliphatic tetraorganostannanes, the variability of the reaction products is much less, so that in nearly all cases only disulfinates, R₂Sn(O₂SR)₂, are formed. The aromatic tin(IV) mono-, di- and tri-sulfinates are also obtained by metathetical reaction between the corresponding organotin halides and sodium sulfinates. A unique feature of triaryltin chlorides, R₃SnCl (R = C₆H₅, o-, m-, p-CH₃C₆H₄), is their disproportionation in liquid SO₂ leading to disulfinates, R₂Sn(O₂SR)₂, and dichlorides, R₂SnCl₂. (p-CH₃C₆H₄)₂SnCl₂, under more efficient conditions, also accepts SO₂ forming (p-CH₃C₆H₄SO₂)₂SnCl₂. The structural investigations of the newly prepared compounds are carried out on the basis of their IR and ¹H NMR spectra.     

A fluorescence study of DNS-labelled chymotrypsin and related enzymes

Various dansyl (DNS)-conjugates of chymotrypsin, chymotrypsinogen and elastase have been prepared. Excitation and emission spectra, and fluorescence depolarization measurements have been obtained in a spectrophotofluorometer, and relevant fluorescent lifetimes have been derived from fluorescence decay measurements.Free DNS-OH gave a lifetime of 13 nsec in fair agreement with other estimates, but combined DNS gave significantly lower values. In particular, ?-DNS lysine in water gave a value of 4 nsec, with higher values (up to 10 nsec) at increasing glycerol concentration. Of the various protein conjugates, specifically labelled chymotrypsin gave the lowest lifetime (6 nsec); for the others, higher values were observed, the values increasing with pH of labelling. Of the protein conjugates, only in the case of specifically labelled elastase, did 'glycerol concentration cause an increase in the measured τ value from 8 to 12 nsec.Active-site labelled chymotrypsin was unusual in that its fluorescent spectrum was dependent upon excitation wavelength and its excitation spectrum upon the selected emission wavelength. The addition of further non-specifically attached DNS-groups caused a shift towards the spectra of such DNS-groups, and saturation with indole gave spectra of such a type as well as erasing wavelength dependence. It seemed that specifically attached DNS groups were probably within the “tosyl hole” but could be dislodged by indole, a competitive inhibitor.Depolarization properties were in all cases markedly dependent upon excitation wavelength. Experiments performed with varying temperature gave relaxation times which were smaller than expected for a rigid molecule with the molecular weight of chymotrypsin but, also, considerable increases were observed with increasing excitation wavelength. It seemed that the susceptibility to temperature-activated rotation of the DNS group increased with the energy of the incident radiation. At constant temperature, apart from specifically-labelled chymotrypsin, spuriously high relaxation times were observed, for which an explanation is required. Until this is provided, depolarization measurements cannot be regarded as providing a sound method of measuring relaxation times of protein molecules in solution.     

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.     

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.