Symmetric Versus Asymmetric “Homologous” Vinylic Cross‐Linkers in Two‐Components Networks: Formation of Pseudo‐Conetworks or Pseudo‐IPNs

Radical copolymerizations of heterologous comonomers are compositionally heterogeneous, unless the reaction is performed in continuous conditions. A bicomponent network prepared from a heterogeneous reaction like the mentioned before is therefore a complex structure where chains with different compositions are linked through the cross‐linker molecules. It is theoretically shown here that the use of cross‐linkers with different structural homologies toward the two comonomers may lead to very different topologies. Thus, a mixture of symmetric cross‐linkers, each one homologous to each comonomer, tends to form interpenetrated networks (IPNs). However, the use of a single bihomologous asymmetric cross‐linker, where each of the functionalities is homologous toward each of the comonomers, tends to form conetworks. It is shown here that the higher the differential reactivity between the groups, the higher is the tendency toward these extreme structures.

     

Synthesis of Pseudo‐Peptides Containing a Quinazolinone Skeleton via Ugi Four‐Component Reaction

A simple and efficient synthesis of quinazolinone pseudo‐peptide derivatives based on a new 3‐amino‐1,2,3,4‐tetrahydro‐4‐oxoquinazoline‐2‐carboxylic acid via Ugi four‐component reaction has been developed. This reaction was conducted under mild conditions with a broad scope of substrates.     

Probing Invisible,Excited Protein States by Non‐Uniformly Sampled Pseudo‐4D CEST Spectroscopy

Chemical exchange saturation transfer (CEST) NMR spectroscopy is a powerful tool for studies of slow timescale protein dynamics. Typical experiments are based on recording a large number of 2D data sets and quantifying peak intensities in each of the resulting planes. A weakness of the method is that peaks must be resolved in 2D spectra, limiting applications to relatively small proteins. Resolution is significantly improved in 3D spectra but recording uniformly sampled data is time‐prohibitive. Here we describe non‐uniformly sampled HNCO‐based pseudo‐4D CEST that provides excellent resolution in reasonable measurement times. Data analysis is done through fitting in the time domain, without the need of reconstructing the frequency dimensions, exploiting previously measured accurate peak positions in reference spectra. The methodology is demonstrated on several protein systems, including a nascent form of superoxide dismutase that is implicated in neurodegenerative disease.     

One‐Pot,Pseudo‐Five‐Component Synthesis of Bis[2‐(arylimino)‐1,3‐thiazolidin‐4‐ones]

Synthesis and characterization of bis[2‐(arylimino)‐1,3‐thiazolidin‐4‐ones] are described. The one‐pot, pseudo‐five‐component reaction of an aliphatic diamine, isothiocyanatobenzene, and dialkyl but‐2‐ynedioate at room temperature in anhydrous CH₂Cl₂ gives the title compound in relatively high yield. Under the same conditions, aromatic 1,2‐diamines yield 2‐(arylimino)‐N‐(enaminoaryl)‐1,3‐thiazolidin‐4‐ones in a pseudo‐four‐component reaction. Their structures were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this type of cyclization is proposed (Scheme 3).     

A Copper‐Carboxylate Layer‐Framework with Pseudo‐­Kagomé Net

A two dimensional coordination polymer with pseudo‐Kagomé net [Cu₃(btc)₂(NH₃)₈(H₂O)] was prepared from Cu(NO₃)₂ · 3H₂O and 1, 3, 5‐benzenetricarboxylic acid (btc) in ammonia aqua solution and was structurally characterized by X‐ray diffraction. The magnetic susceptibility measurements, measured from 2 to 300 K, revealed a weak anti‐ferromagnetic interaction between the Cu^II ions via the btc ligands.     

Sterically stabilized emulsion polymerization of styrene: Pseudo‐semicontinuous approach

The sterically stabilized emulsion polymerization of styrene initiated by a water‐soluble initiator at different temperatures has been investigated. The rate of polymerization (R_p) versus conversion curve shows the two non‐stationary‐rate intervals typical for the polymerization proceeding under non‐stationary‐state conditions. The shape of the R_p versus conversion curve results from two opposite effects—the increased number of particles and the decreased monomer concentration at reaction loci as the polymerization advances. At elevated temperatures the monomer emulsion equilibrates to a two‐phase or three‐phase system. The upper phase is transparent (monomer), and the lower one is blue colored, typical for microemulsion. After stirring such a multiphase system and initiation of polymerization, the initial coarse polymer emulsion was formed. The average size of monomer/polymer particles strongly decreased up to about 40% conversion and then leveled off. The initial large particles are assumed to be highly monomer‐swollen particles formed by the heteroagglomeration of unstable polymer particles and monomer droplets. The size of the “highly monomer” swollen particles continuously decreases with conversion, and they merge with the growing particles at about 40–50% conversion. The monomer droplets and/or large highly monomer‐swollen polymer particles also serve as a reservoir of monomer and emulsifier. The continuous release of nonionic (hydrophobic) emulsifier from the monomer phase increases the colloidal stability of primary particles and the number of polymer particles, that is, the particle nucleation is shifted to the higher conversion region. Variations of the square and cube of the mean droplet radius with aging time indicate that neither the coalescence nor the Ostwald ripening is the main driving force for the droplet instability. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 804–820, 2003     

An Efficient Approach to the Synthesis of Hydrazinyl Pseudo‐Peptides

New hydrazinyl pseudo‐peptides have been obtained from Ugi four‐component reaction (4CR). The 5‐hydrazinyl‐5‐oxopentanoic acids used as starting materials were prepared by the reaction of hydrazides with anhydrides. Mild reaction conditions, high atom economy, bond‐forming efficiency, and easy workup are advantages of this approach. The products have four amide bonds and high potential for H‐bonding.     

Probing Invisible,Excited Protein States by Non‐Uniformly Sampled Pseudo‐4D CEST Spectroscopy

Chemical exchange saturation transfer (CEST) NMR spectroscopy is a powerful tool for studies of slow timescale protein dynamics. Typical experiments are based on recording a large number of 2D data sets and quantifying peak intensities in each of the resulting planes. A weakness of the method is that peaks must be resolved in 2D spectra, limiting applications to relatively small proteins. Resolution is significantly improved in 3D spectra but recording uniformly sampled data is time‐prohibitive. Here we describe non‐uniformly sampled HNCO‐based pseudo‐4D CEST that provides excellent resolution in reasonable measurement times. Data analysis is done through fitting in the time domain, without the need of reconstructing the frequency dimensions, exploiting previously measured accurate peak positions in reference spectra. The methodology is demonstrated on several protein systems, including a nascent form of superoxide dismutase that is implicated in neurodegenerative disease.     

Superoxide Compounds of the Large Pseudo‐Alkali‐Metal Ions Tetramethylammonium, ‐Phosphonium,and ‐Arsonium

Compounds of the three large cations tetramethylammonium, tetramethylphosphonium, and tetramethylarsonium with the superoxide radical anion were synthesized by either metathesis or ion exchange in liquid ammonia. They were obtained from concentrated solutions as ammoniates in the form of long needle‐shaped single crystals. [N(CH₃)₄]‐(O₂)?3NH₃ crystallizes in the monoclinic crystal system, whereas the two compounds [E(CH₃)₄](O₂)?2NH₃ (E=P, As) are isostructural and belong to the orthorhombic crystal system. The cation–anion packing in all three crystal structures is related to the sodium chloride structure. All structures contain hydrogen bonds between the ammonia molecules and between ammonia and the superoxide. The solvent of crystallization was easily released from the crystals upon complete removal of the solvent from the reaction vessel, leading to polycrystalline samples. The Raman spectra of all three solvent‐free compounds show the symmetric stretching mode of the superoxide ion at about 1123 cm^?1. The desolvated [N(CH₃)₄](O₂) was investigated by powder X‐ray diffraction, and the crystal structure was solved by ab initio simulated annealing methods by using rigid‐body models of the constituent molecular ions. The superoxide ion shows rotational disorder. The magnetic susceptibility of tetramethylammonium superoxide follows the Curie–Weiss law with a high‐temperature effective magnetic moment of 1.66(3) μ_B and a paramagnetic Curie temperature of Θ=?13(6) K. Complementary electron paramagnetic resonance spectroscopy revealed that the average g factor is temperature‐dependent. It decreased from 2.15 at 10 K to 1.66 at 100 K, possibly due to the onset of rotational motion of the superoxide ion and in accordance with the lower‐than‐expected effective magnetic moment.     

Pseudo‐Fivefold Diffraction Symmetries in Tetrahedral Packing

We review the way in which atomic tetrahedra composed of metallic elements pack naturally into fused icosahedra. Orthorhombic, hexagonal, and cubic intermetallic crystals based on this packing are all shown to be united in having pseudo‐fivefold rotational diffraction symmetry. A unified geometric model involving the 600‐cell is presented: the model accounts for the observed pseudo‐fivefold symmetries among the different Bravais lattice types. The model accounts for vertex‐, edge‐, polygon‐, and cell‐centered fused‐icosahedral clusters. Vertex‐centered and edge‐centered types correspond to the well‐known pseudo‐fivefold symmetries in I_h and D_5h quasicrystalline approximants. The concept of a tetrahedrally‐packed reciprocal space cluster is introduced, the vectors between sites in this cluster corresponding to the principal diffraction peaks of fused‐icosahedrally‐packed crystals. This reciprocal‐space cluster is a direct result of the pseudosymmetry and, just as the real‐space clusters, can be rationalized by the 600‐cell. The reciprocal space cluster provides insights for the Jones model of metal stability. For tetrahedrally‐packed crystals, Jones zone faces prove to be pseudosymmetric with one another. Lower and upper electron per atom bounds calculated for this pseudosymmetry‐based Jones model are shown to accord with the observed electron counts for a variety of Group 10–12 tetrahedrally‐packed structures, among which are the four known Cu/Cd intermetallic compounds: CdCu₂, Cd₃Cu₄, Cu₅Cd₈, and Cu₃Cd₁₀. The rationale behind the Jones lower and upper bounds is reviewed. The crystal structure of Zn₁₁Au₁₅Cd₂₃, an example of a 1:1 MacKay cubic quasicrystalline approximant based solely on Groups 10–12 elements is presented. This compound crystallizes in Im$\bar 3$ (space group no. 204) with a=13.842(2) Å. The structure was solved with R₁=3.53 %, I>2σ;=5.33 %, all data with 1282/0/38 data/restraints/parameters.     

A new asymmetric Pseudo‐Voigt function for more efficient fitting of XPS lines

Asymmetric peak profiles for the application in spectroscopy can be obtained in a simple way by substituting the usually constant full width at half maximum parameter in Pseudo‐Voigt functions with an energy‐dependent expression, for instance of sigmoidal shape. While this approach has been successfully applied to vibrational spectra, we find that the resulting curves are less suitable for least‐squares fits of X‐ray photoelectron spectroscopy (XPS) data. However, if one additionally allows a variable displacement of the sigmoidal step relative to the peak, excellent fitting results can be obtained. We demonstrate the applicability of our extended approach on several inherently asymmetric XPS lines, i.e. the C 1s signal of graphite and C₂H₂/Pd(100), the 3d_5/2–3d_3/2 doublet of palladium, and the 4f_7/2–4f_5/2 doublet of platinum. Comparison of the corresponding fit results with the results obtained by the application of more elaborate, theory‐based line profiles (Doniach‐?unji? and Mahan functions) shows that the modified Pseudo‐Voigt function gives practically identical results in terms of peak shape and area, while requiring much less computational effort since no convolution procedures are required for its calculation. Thus, this function is most suitable for application in one of the following situations: (i) the peak shape of a given signal is known but cannot be calculated with ease, and (ii) the theoretical peak shape is not (yet) known, however, one wants to perform a first quantitative screening of the data at issue. Copyright © 2014 John Wiley & Sons, Ltd.     

Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor

Pseudo‐natural‐product (NP) design combines natural product fragments to provide unprecedented NP‐inspired compounds not accessible by biosynthesis, but endowed with biological relevance. Since the bioactivity of pseudo‐NPs may be unprecedented or unexpected, they are best evaluated in target agnostic cell‐based assays monitoring entire cellular programs or complex phenotypes. Here, the Cinchona alkaloid scaffold was merged with the indole ring system to synthesize indocinchona alkaloids by Pd‐catalyzed annulation. Exploration of indocinchona alkaloid bioactivities in phenotypic assays revealed a novel class of azaindole‐containing autophagy inhibitors, the azaquindoles. Subsequent characterization of the most potent compound, azaquindole‐1, in the morphological cell painting assay, guided target identification efforts. In contrast to the parent Cinchona alkaloids, azaquindoles selectively inhibit starvation‐ and rapamycin‐induced autophagy by targeting the lipid kinase VPS34.     

Peptide‐Directed DNA‐Templated Protein Labelling for The Assembly of a Pseudo‐IgM

The development of methods for conjugation of DNA to proteins is of high relevance for the integration of protein function and DNA structures. Here, we demonstrate that protein‐binding peptides can direct a DNA‐templated reaction, selectively furnishing DNA–protein conjugates with one DNA label. Quantitative conversion of oligonucleotides is achieved at low stoichiometries and the reaction can be performed in complex biological matrixes, such as cell lysates. Further, we have used a star‐like pentameric DNA nanostructure to assemble five DNA–Rituximab conjugates, made by our reported method, into a pseudo‐IgM antibody structure that was subsequently characterized by negative‐stain transmission electron microscopy (nsTEM) analysis.     

Stimuli‐Responsive Self‐Assembly of a Naphthalene Diimide by Orthogonal Hydrogen Bonding and Its Coassembly with a Pyrene Derivative by a Pseudo‐Intramolecular Charge‐Transfer Interaction

A naphthalene diimide (NDI) building block containing hydrazide (H1) and hydroxy (H2) groups self‐assembled into a reverse‐vesicular structure in methylcyclohexane by orthogonal H‐bonding and π‐stacking. At an elevated temperature (LCST=43 °C), destruction of the assembled structure owing to selective dissociation of H2–H2 H bonding led to macroscopic precipitation. Further heating resulted in homogeneous redispersion of the sample at 70 °C (UCST) and the formation of a reverse‐micellar structure. In the presence of a pyridine (H3)‐functionalized pyrene (PY) donor, a supramolecular dyad (NDI–PY) was formed by H2–H3 H‐bonding. Slow transformation into an alternate NDI–PY stack occurred by a folding process due to the charge‐transfer interaction between NDI and PY. The mixed NDI–PY assembly exhibited a morphology transition from a reverse micelle (with a NDI–PY mixed‐stack core) below the LCST to another reverse micelle (with a NDI core) above the UCST via a “denatured” intermediate.     

Synthesis of Spiropyrazolines via a Pseudo‐Six Component Reaction

A novel and eco‐friendly route for the synthesis of highly functionalized spiropyrazolines via a pseudo‐six component reaction of hydrazine hydrate, nitro ketene dithioacetal, isatin, and active methylene under mild condition at room temperature in ethanol media has been developed. The key steps in the synthetic strategy involve the formation of 1,1‐dihydrazino‐2‐nitroethylene from hydrazine hydrate with nitro ketene dithioacetal and its reaction with Knoevenagel adduct derived from the corresponding isatin and active methylene. The reaction is particularly attractive due to features such as high bond‐forming efficiency, optimum convergence, mild condition, atom economy, easy work‐up/purification, and reduced waste production without using any additive.