The solid-phase Nicholas reaction: scope and limitations

Two libraries of alpha-substituted alkynes has been prepared on solid phase using a sequential Sonogashira/Nicholas reaction approach. The scope of nucleophiles in the Nicholas reaction on solid phase has been investigated, including carbon, oxygen, nitrogen, sulfur, fluoride, and hydride nucleophiles. The conditions for the reaction sequence have been optimized in terms of Lewis acid, catalyst for the Sonogashira step, temperature, reaction time, and decomplexation method, enabling the five-step sequence to be performed in 1 day.     

Synthesis, characterization, and stability of Fe-MCM-41 for production of carbon nanotubes by acetylene pyrolysis

Fe-substituted MCM-41 molecular sieves with ca. 1, 2, and 3 wt % Fe were synthesized hydrothermally using different sources of colloidal silica (HiSil and Cab-O-Sil) and characterized by ICP, XRD, N2 physisorption, UV-vis, EPR, TPR, and X-ray absorption. Catalysts synthesized from Cab-O-Sil showed higher structural order and stability than those from HiSil. The local environment of Fe in the mesoporous material as studied by UV-vis reveals the dominance of framework Fe in all the as-synthesized Fe-MCM-41 samples. Dislodgement of some Fe species to extraframework location occurs upon calcination, and this effect is more severe for Fe-MCM-41 (2 wt %) and Fe-MCM-41 (3 wt %), as confirmed by EPR and X-ray absorption. These materials have been used as catalytic templates for the production of carbon nanotubes (CNTs) by acetylene pyrolysis at atmospheric pressure. A relationship between the Fe loading in MCM-41 and the carbon species produced during this reaction has been established. Using our optimized conditions for this system, Fe-MCM-41 with ca. 2 wt % Fe showed the best results with particularly high selectivity for single-wall carbon nanotube (SWNT) production. This catalyst was selective for carbon nanotubes with a low amount of amorphous carbon for a narrow range of temperatures from 1073 to 1123 K. To account for the different selectivity of these catalysts for CNTs production, the local environment and chemical state of Fe in the used catalyst was further probed by X-band EPR.     

Heat shock protein 27 interacts with vimentin and prevents insolubilization of vimentin subunits induced by cadmium

Vimentin is an intermediate filament that regulates cell attachment and subcellular organization. In this study, vimentin filaments were morphologically altered, and its soluble subunits were rapidly reduced via cadmium chloride treatment. Cadmium chloride stimulated three major mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and led apoptotic pathway via caspase-9 and caspase-3 activations. In order to determine whether MAPKs were involved in this cadmium-induced soluble vimentin disappearance, we applied MAPK-specific inhibitors (PD98059, SP600125, SB203580). These inhibitors did not abolish the cadmium-induced soluble vimentin disappearance. Caspase and proteosome degradation pathway were also not involved in soluble vimentin disappearance. When we observed vimentin levels in soluble and insoluble fractions, soluble vimentin subunits shifted to an insoluble fraction. As we discovered that heat-shock protein 27 (HSP27) was colocalized and physically associated with vimentin in unstressed cells, the roles of HSP27 with regard to vimentin were assessed. HSP27-overexpressing cells prevented morphological alterations of the vimentin filaments, as well as reductions of soluble vimentin, in the cadmium-treated cells. Moreover, HSP27 antisense oligonucleotide augmented these cadmium-induced changes in vimentin. These findings indicate that HSP27 prevents disruption of the vimentin intermediate filament networks and soluble vimentin disappearance, by virtue of its physical interaction with vimentin in cadmium-treated SK-N-SH cells.     

Mechanism of hierarchical porosity development in MFI zeolites by desilication: the role of aluminium as a pore-directing agent

The role of the concentration and the nature of aluminium in the creation of hierarchical porosity in both commercial and synthesized MFI zeolites have been investigated through controlled mesoporosity development by desilication in alkaline medium. Framework aluminium controls the process of framework silicon extraction and makes desilication selective towards intracrystalline mesopore formation. An optimal molar Si/Al ratio in the range 25-50 has been identified; this leads to an optimal mesoporosity centred around 10 nm and mesopore surface areas of up to 235 m(2) g(-1) while preserving the intrinsic crystalline and acidic properties. At lower framework Si/Al ratios the relatively high Al content inhibits Si extraction and hardly any mesopores are created, while in highly siliceous ZSM-5 unselective extraction of framework Si induces formation of large pores. The existence of framework Al sites in different T positions that are more or less susceptible to the alkaline treatment, and the occurrence of re-alumination, are tentative explanations for the remarkable behaviour of Al in the desilication process. The presence of substantial extra framework Al, obtained by steam treatment, inhibits Si extraction and related mesopore formation; this is attributed to re-alumination of the extraframework Al species during the alkaline treatment. Removal of extraframework Al species by mild oxalic acid treatment restores susceptibility to desilication, which is accompanied by formation of larger mesopores due to the enhanced Si/Al ratio in the acid-treated zeolite.     

The effect of (natural) polyols on the initial colour of heavy metal- and zinc-free poly(vinyl chloride)

The propensity of (natural) polyols dispersed in heavy metal- and zinc-free PVC sheets to improve the initial colour, e.g. the colour during the first minutes of exposure to high processing temperatures (short-term stability), has been investigated. It is shown using W(Lab) values that the initial colour improves upon addition of polyols containing primary hydroxyl groups. The polyols act as HCl scavengers, presumably via an acid-catalysed S_N2 substitution of the primary hydroxyl groups by chloride ions. In contrast, polyols with only secondary or tertiary hydroxyl groups accelerate the thermal degradation of PVC. Notwithstanding, the efficacy of the (natural) polyols containing primary hydroxyl groups will be reduced if the polyol is susceptible to competitive acid-catalysed intramolecular cyclodehydration reactions under the processing conditions. This is substantiated by a comparison of the behaviour of mannitol and 3,4-di-O-methyl-d-mannitol. The methylated derivative, which is less prone to undergo intramolecular cyclodehydration, improves the initial colour of heavy metal- and zinc-free PVC sheets more significantly than mannitol itself.     

Spectroscopy and quantum chemical modeling reveal a predominant contribution of excitonic interactions to the bathochromic shift in alpha-crustacyanin, the blue carotenoprotein in the carapace of the lobster Homarus gammarus

To resolve the molecular basis of the coloration mechanism of alpha-crustacyanin, we used (13)C-labeled astaxanthins as chromophores for solid-state (13)C NMR and resonance Raman spectroscopy of [6,6',7,7']-(13)C(4) alpha-crustacyanin and [8,8',9,9',10,10',11,11',20,20']-(13)C(10) alpha-crustacyanin. We complement the experimental data with time-dependent density functional theory calculations on several models based on the structural information available for beta-crustacyanin. The data rule out major changes and strong polarization effects in the ground-state electron density of astaxanthin upon binding to the protein. Conformational changes in the chromophore and hydrogen-bond interactions between the astaxanthin and the protein can account only for about one-third of the total bathochromic shift in alpha-crustacyanin. The exciton coupling due to the proximity of two astaxanthin chromophores is found to be large, suggesting that aggregation effects in the protein represent the primary source of the color change.     

Factors affecting gas-phase deuterium scrambling in peptide ions and their implications for protein structure determination

In this report, we evaluate the validity of using hydrogen/deuterium exchange in combination with collision-induced dissociation mass spectrometry (CID MS) for the detailed structural and conformational investigation of peptides and proteins. This methodology, in which partly deuterated peptide ions are subjected to collision-induced dissociation in the vacuum of a mass spectrometer, has emerged as a useful tool in structural biology. It may potentially provide quantitatively the extent of deuterium incorporation per individual amino acid in peptides and proteins, thus providing detailed structural information related to protein structure and folding. We report that this general methodology has limitations caused by the fact that the incorporated deuterium atoms migrate prior or during the CID MS analysis. Our data are focused on a variety of transmembrane peptides, incorporated in a lipid bilayer, in which the near-terminal amino acids that anchor at the lipid-water interface are systematically varied. Our findings suggest that, under the experimental conditions we use, the extent of intramolecular hydrogen scrambling is strongly influenced by experimental factors, such as the exact amino acid sequence of the peptide, the nature of the charge carrier, and therefore most likely by the gas-phase structure of the peptide ion. Moreover, the observed scrambling seems to be independent of the nature of the peptide fragment ions (i.e., protonated B and Y' ' ions, and sodiated A and Y' ions). Our results strongly suggest that scrambling may be reduced by using alkali metal cationization instead of protonation in the ionization process.     

Site-selective labeling strategies for screening by NMR

NMR based screening has become an important tool in the pharmaceutical industry. Methods that provide information on the location of small molecule binding sites on the surface of a drug target (e. g. SAR-by-NMR and related techniques) are of particular interest. In order to extend the applicability of such techniques to drug targets of higher molecular weight, selective labeling strategies may be employed. Dual-amino acid selective labeling and site directed non-native amino acid replacement (SNAAR) allow for the selective detection of NMR resonances of a specific amino acid residue. This results in significantly reduced spectral complexity, which not only enables application to higher molecular weight systems, but also eliminates the need for sequential resonance assignment in order to identify the binding site. Regio-selective (or segmental) labeling of an entire protein domain of a multi domain protein may also be achieved. Labeling only a selected part of a multi domain protein (e. g. a catalytic or ligand binding domain) is an attractive way to simplify the spectral interpretation without disturbing the system under study.     

Cyclometallated Pd(II) azido complexes containing 6-phenyl-2,2'-bipyridyl or 2-phenylpyridyl derivatives: synthesis and reactivity toward organic isocyanides and isothiocyanates

Cyclometallated palladium(II) azido complexes containing C,N,N- or C,N-donor ligands, [Pd(N(3))L](HL = 6-phenyl-2,2'-bipyridine or 2-phenylpyridyl derivatives), showed different reactivities toward organic isocyanides and isothiocyanates. In particular, aryl isocyanides (CN-Ar) underwent insertion into the orthometallated Pd-C bond on the phenyl moiety of the supporting ligand (L) in [Pd(N(3))L] or [Pd(N(3))(PR(3))L] to selectively give carbodiimido [[Pd(N=C=N-Ar)L]], imidoyl [[Pd(N(3))(-C=N-Ar)(PR(3))L]], or imidoyl carbodiimido complexes [[Pd(N=C=N-Ar)(-C=N-Ar)L] or [Pd(N=C=N-Ar)(-C=N-Ar)(PR(3))L]], depending on reaction conditions. Interestingly, reactions of [Pd(N(3))(PR(3))L] with organic isothiocyanates gave unusual dinuclear complexes [(micro-SCN(4)-R)PdL](2), exhibiting the concurrent S- and N-coordinating thio-tetrazole bridge.     

Solvent effects on charge transport through solid deposits of [Os(4,4'-diphenyl-2,2'-dipyridyl)2Cl2

Mechanically attached, solid-state films of [Os(4,4'-diphenyl-2,2'-dipyridyl)2Cl2] have been formed on gold macro- and microelectrodes and their voltammetric properties investigated. The voltammetric response of these films associated with the Os(2+/3+) redox reaction is reminiscent of that observed for an ideal reversible, solution phase redox couple only when the contacting electrolyte contains of the order of 40% v/v of acetonitrile (ACN). The origin of this effect appears to involve preferential solvation of the redox centres by acetonitrile which facilitates the incorporation of charge compensating counterions. Scanning electron microscopy reveals that voltammetric cycling in 40:60 ACN-H2O containing 1.0 M LiClO4 as the electrolyte induces the formation of microcrystals. Voltammetry conducted under semi-infinite linear diffusion conditions has been used to determine the apparent diffusion coefficient, Dapp, for homogeneous charge transport through the deposit. The dynamics of charge transport decrease with increasing film thickness but appear to increase with increasing electrolyte concentration. These observations suggest that ion transport rather than the rate of electron self-exchange limit the overall rate of charge transport through these solids. When in contact with 40:60 ACN-H2O containing 1.0 M LiClO4 as electrolyte, Dapp values for oxidation and reduction are identical at 1.7 +/- 0.4 x 10(-12) cm2 s(-1). In the same electrolyte, the standard heterogeneous electron transfer rate constant, k(o), determined by fitting the full voltammogram using the Butler-Volmer formalism, is 8.3 +/- 0.5 x 10(-7) cm s(-1). The importance of these results for the rational design of solid state redox active materials for battery, display and sensor applications is considered.