Surprising Stability Research Articles

Controlling Regioselectivity in the Enantioselective N-Alkylation of Indole Analogues Catalyzed by Dinuclear Zinc-ProPhenol.

The enantioselective N-alkylation of indole and its derivatives with aldimines is efficiently catalyzed by a zinc-ProPhenol dinuclear complex under mild conditions to afford N-alkylated indole derivatives in good yield (up to 86 %) and excellent enantiomeric ratio (up to 99.5:0.5 e.r.). This method tolerates a wide array of indoles, as well as pyrrole and carbazole, to afford the corresponding N-alkylation products. The reaction can be run on a gram scale with reduced catalyst loading without impacting the efficiency. The chiral aminals were further elaborated into various chiral polyheterocyclic derivatives. The surprising stability of the chiral N-alkylation products will open new windows for asymmetric catalysis and medicinal chemistry.

Controlling Regioselectivity in the Enantioselective N‐Alkylation of Indole Analogues Catalyzed by Dinuclear Zinc‐ProPhenol

AbstractThe enantioselective N‐alkylation of indole and its derivatives with aldimines is efficiently catalyzed by a zinc‐ProPhenol dinuclear complex under mild conditions to afford N‐alkylated indole derivatives in good yield (up to 86 %) and excellent enantiomeric ratio (up to 99.5:0.5 e.r.). This method tolerates a wide array of indoles, as well as pyrrole and carbazole, to afford the corresponding N‐alkylation products. The reaction can be run on a gram scale with reduced catalyst loading without impacting the efficiency. The chiral aminals were further elaborated into various chiral polyheterocyclic derivatives. The surprising stability of the chiral N‐alkylation products will open new windows for asymmetric catalysis and medicinal chemistry.

Mammalian Systems Biotechnology Reveals Global Cellular Adaptations in a Recombinant CHO Cell Line

Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At thegenomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected. Subsequent integration of transcriptomic data with a genome-scale metabolic model showed a substantial increase in energy metabolism in the antibody producer. Metabolomics, lipidomics, and glycomics analyses revealed an elevation in long-chain lipidspecies, potentially associated with protein transport and secretion requirements, and a surprising stability of N-glycosylation profiles between both cell lines. Overall, the proposed knowledge-based systems biotechnology framework can further accelerate mammalian cell-line engineering in a targeted manner.

Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid thioesters.

Biotin is an essential vitamin in plants and mammals, functioning as the carbon dioxide carrier within central lipid metabolism. Bacterial pimeloyl-CoA synthetase (BioW) acts as a highly specific substrate-selection gate, ensuring the integrity of the carbon chain in biotin synthesis. BioW catalyzes the condensation of pimelic acid (C7 dicarboxylic acid) with CoASH in an ATP-dependent manner to form pimeloyl-CoA, the first dedicated biotin building block. Multiple structures of Bacillus subtilis BioW together capture all three substrates, as well as the intermediate pimeloyl-adenylate and product pyrophosphate (PPi), indicating that the enzyme uses an internal ruler to select the correct dicarboxylic acid substrate. Both the catalytic mechanism and the surprising stability of the adenylate intermediate were rationalized through site-directed mutagenesis. Building on this understanding, BioW was engineered to synthesize high-value heptanoyl (C7) and octanoyl (C8) monocarboxylic acid-CoA and C8 dicarboxylic-CoA products, highlighting the enzyme's synthetic potential.

Phosphenium Hydride Reduction of [(cod)MX2] (M = Pd, Pt; X = Cl, Br): Snapshots on the Way to Phosphenium Metal(0) Halides and Synthesis of Metal Nanoparticles

The outcome of the reduction of [(cod)PtX2] (X = Cl, Br; cod = 1,5-cyclooctadiene) with N-heterocyclic phosphenium hydrides RNHP-H depends strongly on the steric demand of the N-aryl group R and the nature of X. Reaction of [(cod)PtCl2] with DippNHP-H featuring bulky N-Dipp groups produced an unprecedented monomeric phosphenium metal(0) halide [(DippNHP)(DippNHP-H)PtCl] stabilized by a single phosphine ligand. The phosphenium unit exhibits a pyramidal coordination geometry at the phosphorus atom and may according to DFT calculations be classified as a Z-type ligand. In contrast, reaction of [(cod)PtBr2] with the sterically less protected MesNHP-H afforded a mixture of donor-ligand free oligonuclear complexes [{(MesNHP)PtBr}n] (n = 2, 3), which are structural analogues of known palladium complexes with μ2-bridging phosphenium units. All reductions studied proceed via spectroscopically detectable intermediates, several of which could be unambiguously identified by means of multinuclear (1H, 31P, 195Pt) NMR spectroscopy and computational studies. The experimental findings reveal that the phosphenium hydrides in these multistep processes adopt a dual function as ligands and hydride transfer reagents. The preference for the observed intricate pathways over seemingly simpler ligand exchange processes is presumably due to kinetic reasons. The attempt to exchange the bulky phosphine ligand in [(DippNHP)(DippNHP-H)PtCl] by Me3P resulted in an unexpected isomerization to a platinum(0) chlorophosphine complex via a formal chloride migration from platinum to phosphorus, which accentuates the electrophilic nature of the phosphenium ligand. Phosphenium metal(0) halides of platinum further show a surprising thermal stability, whereas the palladium complexes easily disintegrate upon gentle heating in dimethyl sulfoxide to yield metal nanoparticles, which were characterized by TEM and XRD studies.

Folding in Pieces

Circulating inhibitory serpins regulate important physiological processes including inflammation. Misfolding and polymerization of serpins in the endoplasmic reticulum (ER) can lead to both loss-of-function and gain-of-function diseases. The topology of the two-domain, non-sequential serpin fold is complicated with both the αβ and mainly β domains containing regions from near the N- and the C-termini. Despite these complications recent molecular dynamics simulations of serpin folding suggest that significant amounts of local secondary structure forms and rearranges for long-range contact formation resulting in the folded, active serpin. This folding pathway requires a balance between local structural stability and the flexibility/dynamics needed for long-range contact formation. To help test this proposed mechanism, we expressed and characterized N- to C-terminal fragments of the canonical, 394 residue serpin α1-antitrypsin (Alpha1). Even the shortest, 150 residue long, fragment showed cooperative unfolding and surprising stability with a denaturation midpoint of 1.9 M guanidinium hydrochloride. Nonetheless, the far-UV circular dichroism (CD) spectra differ from the spectra predicted for the full-length, native protein. Similarly, fluorescence emission of the longest fragment, 1-323, exhibited the hyper-fluorescent signature of the unfolding/folding intermediate observed during equilibrium denaturation or refolding of full-length Alpha1. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) was used to better define the structure of the fragments. After 10 seconds of deuteration, significant protection is observed in parts of the N-terminal region of the αβ domain, and for longer fragments in some of the β strands that form the core of the β domain. These results suggest that surprisingly stable local structures can be formed by fragments of the serpin Alpha1 and are consistent with models for serpin folding derived from molecular dynamics simulations. The results also suggest that significant amounts of serpin structure might form co-translationally.

The formation of CdS quantum dots and Au nanoparticles

Abstract We report on microsecond-resolved in-situ SAXS experiments of the early nucleation and growth behavior of both cadmium sulfide (CdS) quantum dots in aqueous solution including the temperature dependence and of gold (Au) nanoparticles. A novel free-jet setup was developped to access reaction times as early as 20 μs. As the signal in particular in the beginning of the reaction is weak the containment-free nature of this sample environment prooved crucial. The SAXS data reveal a two-step pathway with a surprising stability of a structurally relaxed cluster with a diameter of about 2 nm. While these develop rapidly by ionic assembly, a further slower growth is attributed to cluster attachment. WAXS diffraction confirms, that the particles at this early stage are not yet crystalline. This growth mode is confirmed for a temperature range from 25°C to 45°C. An energy barrier for the diffusion of primary clusters in water of 0.60 eV was experimentally observed in agreement with molecular simulations. To access reaction times beyond 100 ms, a stopped-drop setup -again contaiment- free is introduced. SAXS experiments on the growth of Au nanoparticles on an extended time scale provide a much slower growth with one population only. Further, the influence of ionizing X-ray radiation on the Au particle fromation and growth is discussed.

Triethynylmethanol Derivatives: Stable Acetylenic Building Blocks for Surface Chemistry.

The synthesis of non-conjugated, carbon-rich building blocks is described, based on a basic scaffold of triethynylmethanol (TEtM). The substitution of the ethynyl groups can be easily varied (including R3 Si, H, Br), and this allows structural tuning for stabilization, synthetic derivatization, and adsorption on Ag(111) or Au(111). X-ray crystallography helps to explain the surprising stability of the selected derivatives in the solid state, and an unusual form of hydrogen bonding is identified from these analyses. Preliminary efforts to achieve surface-based reactions on Ag(111) and Au(111) are outlined experimentally and computationally.

PTV gap as a new measure of partisanship: a panel-data, multi-measure validation showing surprising partisanship stability

ABSTRACTComparative studies of partisanship lack a comparable transatlantic measure. In the U.S. the traditional ANES measure is used, while in European multi-party systems a party-closeness measure is mostly used. A recent contribution proposed PTV (propensity-to-vote) gap as a potential solution to this issue, showing that the gap in PTV scores between the best- and the second best-placed party has desirable properties in the American case. In this article we test the same measure on the multi-party case of Italy, using panel data from the CISE 2012–2013 Electoral Panel.The case is particularly relevant, given the turbulence experienced by the Italian party system at the time, with the emergence of important new parties. This makes this period a crucial test for performing a validation of party identification measures. Comparing the new measure with the traditional party-closeness measure, we show that: a) both measures are more stable than vote choice, in line with party identification theory, and contrary to previous research on other European multi-party systems; b) the two measures are virtually equivalent in terms of over-time stability. As a second comparative validation, we investigate the mutual effects relating partisanship and vote over time. Results show superiority for the PTV-gap measure, which has similar predictive power on vote choice, but in turn is predicted by it to a statistically inferior extent. As a result, we conclude that our validation of the PTV-gap measure– already successfully tested in the U.S. context – qualifies it as a productive tool for comparative research on partisanship.

Structural investigation of cyclo-dioxo maleimide cross-linkers for acid and serum stability.

The biochemical characteristics of hetero-bifunctional cross-linkers used in bioconjugates are of essential importance to the desired features of the final adduct (i.e. antibody-drug conjugates). These include stability in biological media, chemical and biological reactivities, cleavability under defined conditions, and solubility. In our previous work, we introduced a new amino-to-thiol linker, maleimidomethyl dioxane (MD), as an alternative to classical maleimide conjugation, with increased hydrophilicity and serum stability due to succinimidyl ring-opening. In this work, we investigate the generality of linkers containing a dioxo-ring with regard to their ability to self-hydrolyze and their surprising stability at a low pH. We synthesized four FRET probes which allowed us to address the stability of the dioxo-ring and to study the maleimide ring-opening and the thiol-exchange processes by means of detecting and measuring the generation of fluorescence. It was found that the ring expansion (from a 5- to a 6-membered ring) improved the stability of the probes in aqueous media, and the increase of the chain length between the dioxo-ring and the succinimide ring (from methylene to ethylene) decreased the rate of succinimidyl ring-opening.

Joint experimental and theoretical studies of the surprising stability of the aryl pentazole upon noncovalent binding to β-cyclodextrin.

Herein, binding of the β-cyclodextrin (β-CD) host to the unstable aryl pentazole guest has been confirmed experimentally and theoretically. After the confinement of aryl pentazole, electron density reorganization was studied by M06-2X dispersion-corrected DFT and further reflected in the characteristic shift in the NMR spectra. Among the host-guest complexes, the inclusion complex is favored with the phenyl ring expectedly encapsulated within the cavity through noncovalent interactions such as hydrogen bonding, C-Hπ, and the special Csp2-HH-Csp3 bonding discovered by the NBO, QTAIM, and NCI-RDG theories. The host-guest binding renders the enhancement of the nitrogen-ring aromatic character; this has been analyzed by employing nucleus-independent chemical shift (NICS)-based profiles. The non-covalent interaction largely enhances the thermal stability of the guest through a change of the decomposition reaction path whether the guest is encapsulated or not by the host. By comparison of the structures of B1-B4, the enhancement could be assigned to the ion-type transition structure stabilized by the C-H bonds of the host.

3'-Pyrene-modified unlocked nucleic acids: synthesis, fluorescence properties and a surprising stabilization effect on duplexes and triplexes.

Efficient synthesis of a new 3'-O-amino-UNA monomer was developed as a scaffold for further functionalization and incorporation into oligonucleotides (ONs). Pyrene-functionalized 3'-O-amino-UNA was incorporated one, two or three times into 21-mer DNA and 2'-O-Me-RNA ONs. Duplex melting temperatures, circular dichroism (CD) spectra, steady-state fluorescence emission spectra, UV/Vis absorption spectra and triplex melting temperatures were measured for the modified duplexes. The presence of the pyrene-modified UNA monomer lead to a surprising and unprecedented thermal stabilization of especially DNA:DNA duplexes when compared to the corresponding unmodified DNA:DNA duplexes. Improved mismatch discrimination was also seen for some of the modified duplexes. CD spectra revealed no major differences between modified and unmodified duplexes. Molecular modeling showed that the pyrene moieties were located in the minor groove of DNA:DNA duplexes as confirmed by CD and UV/Vis absorption studies. Upon multiple incorporations of the monomer in single-stranded ONs, steady-state fluorescence emission studies revealed the formation of a pyrene excimer which in most cases was quenched upon duplex hybridization, and fluorescence-based detection of mismatched hybridization was observed for some modified strand constitutions. Incorporation of the monomer in a triplex-forming oligonucleotide (TFO) strand lead to an increase of triplex melting temperature both at pH 6.0 and pH 7.0 for parallel triplexes - again an effect that has not been reported earlier for UNA-containing ONs. Steady-state fluorescence emission studies revealed significant differences in fluorescence for single-stranded ONs and triplexes.

Synthesis of chitin nanofibers, MWCNTs and MnO2 nanoflakes 3D porous network flexible gel-film for high supercapacitive performance electrodes

As the porous structure and conductivity result in improvement of electrochemical properties, the chitin nanofibers (ChNFs), multi-walled carbon nanotubes (MWCNTs) and MnO2 (manganese dioxide) nanoflakes 3D porous network core-shell structure gel-film was fabricated for flexible free-standing supercapacitor electrodes. The electrodes were characterized by various techniques and the results demonstrate that the as-synthesized ChNFs/MWCNTs/MnO2 gel-film electrodes exhibits excellent supercapacitive behaviours. The ChNFs/MWCNTs/MnO2 gel-film electrode shows a high capacitance of 295.2mF/cm2 at 0.1mA/cm2 in 1M Na2SO4 aqueous electrolyte because of its 3D porous structure. Furthermore, the electrodes also showed surprising cycling stability for 5000cycles with retention rate up to 157.14% at 1mA/cm2. The data presents great promise in the application of high-performance flexible supercapacitors with the low cost, light-weight and excellent cycling ability.

Interference features in scanning gate conductance maps of quantum point contacts with disorder

We consider quantum point contacts (QPCs) defined within disordered two-dimensional electron gases as studied by scanning gate microscopy. We evaluate the conductance maps in the Landauer approach and wave function picture of electron transport for samples with both low and high electron mobility at finite temperatures. We discuss the spatial distribution of the impurities in the context of the branched electron flow. We reproduce the surprising temperature stability of the experimental interference fringes far from the QPC. Next, we discuss -- previously undescribed -- funnel-shaped features that accompany splitting of the branches visible in previous experiments. Finally, we study elliptical interference fringes formed by an interplay of scattering by the point-like impurities and by the scanning probe. We discuss the details of the elliptical features as functions of the tip voltage and the temperature, showing that the first interference fringe is very robust against the thermal widening of the Fermi level. We present a simple analytical model that allows for extraction of the impurity positions and the electron gas depletion radius induced by the negatively charged tip of the atomic force microscope, and apply this model on experimental scanning gate images showing such elliptical fringes.

Neutral zero-valent s-block complexes with strong multiple bonding.

The metals of the s block of the periodic table are well known to be exceptional electron donors, and the vast majority of their molecular complexes therefore contain these metals in their fully oxidized form. Low-valent main-group compounds have recently become desirable synthetic targets owing to their interesting reactivities, sometimes on a par with those of transition-metal complexes. In this work, we used stabilizing cyclic (alkyl)(amino)carbene ligands to isolate and characterize the first neutral compounds that contain a zero-valent s-block metal, beryllium. These brightly coloured complexes display very short beryllium-carbon bond lengths and linear beryllium coordination geometries, indicative of strong multiple Be-C bonding. Structural, spectroscopic and theoretical results show that the complexes adopt a closed-shell singlet configuration with a Be(0) metal centre. The surprising stability of the molecule can be ascribed to an unusually strong three-centre two-electron π bond across the C-Be-C unit.

ChemInform Abstract: Thiohydroximic Acids: Versatile Reagents for Organic Synthesis

AbstractReview: [47 refs.

Crystal Field Splitting is Limiting the Stability and Strength of Ultra-incompressible Orthorhombic Transition Metal Tetraborides.

The lattice stability and mechanical strengths of the supposedly superhard transition metal tetraborides (TmB4, Tm = Cr, Mn and Fe) evoked recently much attention from the scientific community due to the potential applications of these materials, as well as because of general scientific interests. In the present study, we show that the surprising stabilization of these compounds from a high symmetry to a low symmetry structure is accomplished by an in-plane rotation of the boron network, which maximizes the in-plane hybridization by crystal field splitting between d orbitals of Tm and p orbitals of B. Studies of mechanical and electronic properties of TmB4 suggest that these tetraborides cannot be intrinsically superhard. The mechanical instability is facilitated by a unique in-plane or out-of-plane weakening of the three-dimensional covalent bond network of boron along different shear deformation paths. These results shed a novel view on the origin of the stability and strength of orthorhombic TmB4, highlighting the importance of combinational analysis of a variety of parameters related to plastic deformation of the crystalline materials when attempting to design new ultra-incompressible, and potentially strong and hard solids.

An Efficient, Regioselective Pathway to Cationic and Zwitterionic N-Heterocyclic Cellulose Ionomers.

Cationic derivatives of cellulose and other polysaccharides are attractive targets for biomedical applications due to their propensity for electrostatically binding with anionic biomolecules, such as nucleic acids and certain proteins. To date, however, relatively few practical synthetic methods have been described for their preparation. Herein, we report a useful and efficient strategy for cationic cellulose ester salt preparation by the reaction of 6-bromo-6-deoxycellulose acetate with pyridine or 1-methylimidazole. Dimethyl sulfoxide solvent favored this displacement reaction to produce cationic cellulose acetate derivatives, resulting in high degrees of substitution (DS) exclusively at the C-6 position. These cationic cellulose derivatives bearing substantial, permanent positive charge exhibit surprising thermal stability, dissolve readily in water, and bind strongly with a hydrophilic and anionic surface, supporting their potential for a variety of applications such as permeation enhancement, mucoadhesion, and gene or drug delivery. Expanding upon this chemistry, we reacted a 6-imidazolyl-6-deoxycellulose derivative with 1,3-propane sultone to demonstrate the potential for further elaboration to regioselectively substituted zwitterionic cellulose derivatives.

Surprising stability of neutral interstitial hydrogen in diamond and cubic BN

In virtually all semiconductors and insulators, hydrogen interstitials () act as negative-U centers, implying that hydrogen is never stable in the neutral charge state. Using hybrid density functional calculations, we find a different behavior for in diamond and cubic BN. In diamond, is a very strong positive-U center, and the charge state is stable over a Fermi-level range of more than 2 eV. In cubic BN, a III–V compound similar to diamond, we also find positive-U behavior, though over a much smaller Fermi-level range. These results highlight the unique behavior of in these covalent wide-band-gap semiconductors.

Ultraflexible, large-area, physiological temperature sensors for multipoint measurements

We report a fabrication method for flexible and printable thermal sensors based on composites of semicrystalline acrylate polymers and graphite with a high sensitivity of 20 mK and a high-speed response time of less than 100 ms. These devices exhibit large resistance changes near body temperature under physiological conditions with high repeatability (1,800 times). Device performance is largely unaffected by bending to radii below 700 µm, which allows for conformal application to the surface of living tissue. The sensing temperature can be tuned between 25 °C and 50 °C, which covers all relevant physiological temperatures. Furthermore, we demonstrate flexible active-matrix thermal sensors which can resolve spatial temperature gradients over a large area. With this flexible ultrasensitive temperature sensor we succeeded in the in vivo measurement of cyclic temperatures changes of 0.1 °C in a rat lung during breathing, without interference from constant tissue motion. This result conclusively shows that the lung of a warm-blooded animal maintains surprising temperature stability despite the large difference between core temperature and inhaled air temperature.