Non-equilibrium cooling of Poncirus trifoliata (L.) embryonic axes at various water contents

The present study investigated the rate of temperature change within axes of Poncirus trifoliata during cooling and warming by various methods. Cooling rates ranged between 0.17 and 170 degree (C per second, and warming rates of 1.25 and 600 degree C per second were measured when axes were warmed at room temperature or in water at 40 degree C, respectively. Partial drying increased the cooling rate within axes in direct contact with the cryogen, but did not affect the cooling or warming rates within axes enclosed in a double layer of lightweight aluminium foil. The procedures described illustrate the orders of magnitude that separate extremes of the range of cooling or warming rates attained using methods commonly employed in cryopreservation studies. Quantifying these rates allows the relationship between cooling rate, water content and survival of hydrated embryonic axes to be explored.     

Universal covers for Hausdorff limits of noncompact spaces

We prove that if is the Gromov-Hausdorff limit of a sequence of complete manifolds, , with a uniform lower bound on Ricci curvature, then has a universal cover.

     

Development of small molecules that mimic the binding of ω-conotoxins at the N-type voltage-gated calcium channel

Cone snails (Conidae) are marine predators with some extraordinary features. Their venom contains a hundred or more peptides that target numerous ion channels and receptors in mammals, including several that are involved in disease. omega-Conotoxins from fish hunting snails are 24-27 residue peptides with a rigid 4-loop cysteine framework that target the N-type voltage-gated calcium channel (VGCC). Two omega-conotoxins, MVIIA and CVID are currently in clinical development for chronic pain management (Ziconotide or Prialt, and AM336, respectively). In an attempt to develop small molecule equivalents of CVID, we defined the Calpha-Cbeta vectors of the residues believed to be important for binding to the N-type VGCC. Using these vectors, we undertook a virtual screening of virtual libraries approach to identify compounds that matched the pharmacophore. Cyclic pentapeptides containing residues of loop 2 of CVID, with one or more being a D-amino acid were designed and synthesised and were found to be active at the N-type VGCC (IC50 approximately 20 microM). Agreeing with the specificity profile of CVID, molecules were inactive at the P/Q-type VGCC.     

Bidentate NHC-based chiral ligands for efficient Cu-catalyzed enantioselective allylic alkylations: structure and activity of an air-stable chiral Cu complex

Cu-catalyzed addition of alkylzinc reagents to a range of allylic phosphates is promoted efficiently and with high enantioselectivity to afford tertiary as well as quaternary carbon centers (up to 98% ee). Reactions proceed to completion with 0.5-5 mol % catalyst loading and are best promoted by commercially available CuCl2.2H2O. The X-ray structure of the chiral NHC-Ag(I) complex used in the study as well as that of a catalytically active NHC-Cu(II) complex are also reported; both complexes are air-stable and are formed in >/=95% isolated yield. The isolated Cu complex, which can be handled in air, is catalytically active. The present report provides the first precedent for efficient Cu-catalyzed allylic alkylations with chiral NHC ligands.     

Identification of non-idealities in gel electrophoresis

The molecular weight separation, which is the second dimension of two-dimensional gel electrophoresis, is studied quantitatively with the goal of improving positional predictability and reproducibility. Mathematical modeling of carrier electrolyte dynamics is used to track the progress of a stacking front as a function of coulombs passed. In all test cases, the front moves more slowly than predicted and shows both curvature and tilt. These systematic deviations from the model are found to be influenced by a variety of factors, including both design and operating features. These factors are largely explained, and suggestions are made for improvements.     

X-ray structures of new substituted 2-(pyrazol-1-yl)-2′-nitroacetanilides with pharmacological activity

The X-ray structures of four pharmacologically active lidocaine analogs, containing substituted pyrazole moieties as the basic residue and an o-nitrophenyl moiety as the hydrophobic residue, have been determined. They are 2-(pyrazol-1-yl)-2-nitroacetanilide (1), 2-(3,5-dimethyl-pyrazol-1-yl)-2-nitroacetanilide (2), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-2-nitroacetanilide (3), and 2-(3,5-dimethyl-4-nitro-pyrazol-1-yl)-2-nitroacetanilide (4). Crystal data are 1: space group Pn with a = 4.6944(1), b = 22.3890(3), c = 15.7481(2) Å, = 96.810(1)°, Z = 6; 2: P with a = 4.7277(2), b = 11.6878(5), c = 12.0355(6) Å, = 87.689(2), = 85.048(2), = 85.975(2)°, Z = 2; 3: I2/a with a = 24.108(5), b = 4.7321(9), c = 25.337(5) Å, = 96.09(3)°, Z = 8; 4: P2₁ with a = 5.7788(2), b = 8.9844(3), c = 14.0304(5) Å, = 101.611(1)°, Z = 2. Molecules of compound 1 adopt a unique, folded conformation stabilized by intramolecular hydrogen bonds and the crystal structure lacks significant intermolecular interactions. In contrast, molecules of 2–4 adopt common, extended conformations and their crystal structures are based on linear arrays of hydrogen bonded (N—H...O=C) molecules. Compound 3 displayed the highest local anesthetic activity while 2 was the most active in tests for anti-arrhythmic effects.     

Formation of a Highly Reactive Cobalt Nanocluster Crystal within a Highly Negatively Charged Porous Coordination Cage

Earth‐abundant first‐row transition‐metal nanoclusters (NCs) have been extensively investigated as catalysts. However, their catalytic activity is relatively low compared with noble metal NCs. Enhanced catalytic activity of cobalt NCs can be achieved by encapsulating Co NCs in soluble porous coordination cages (PCCs). Two cages, PCC‐2a and 2b, possess almost identical cavity in shape and size, while PCC‐2a has five times more net charges than PCC‐2b. Co²⁺ cations were accumulated in PCC‐2a and reduced to ultra‐small Co NCs in situ, while for PCC‐2b, only bulky Co particles were formed. As a result, Co NCs@PCC‐2a accomplished the highest catalytic activity in the hydrolysis of ammonium borane among all the first‐row transition‐metals NCs. Based on these results, it is envisioned that confining in the charged porous coordination cage could be a novel route for the synthesis of ultra‐small NCs with extraordinary properties.     

A Vastly Increased Chemical Variety of RNA Modifications Containing a Thioacetal Structure

Recently discovered new chemical entities in RNA modifications have involved surprising functional groups that enlarge the chemical space of RNA. Using LC‐MS, we found over 100 signals of RNA constituents that contained a ribose moiety in tRNAs from E. coli. Feeding experiments with variegated stable isotope labeled compounds identified 37 compounds that are new structures of RNA modifications. One structure was elucidated by deuterium exchange and high‐resolution mass spectrometry. The structure of msms²i⁶A (2‐methylthiomethylenethio‐N6‐isopentenyl‐adenosine) was confirmed by methione‐D3 feeding experiments and by synthesis of the nucleobase. The msms²i⁶A contains a thioacetal, shown in vitro to be biosynthetically derived from ms²i⁶A by the radical‐SAM enzyme MiaB. This enzyme performs thiomethylation, forming ms²i⁶A from i⁶A in a first turnover. The new thioacetal is formed by a second turnover. Along with the pool of 36 new modifications, this work describes a new layer of RNA modification chemistry.     

Asymmetric Synthesis of (R)‐1‐Alkyl‐Substituted Tetrahydro‐ß‐carbolines Catalyzed by Strictosidine Synthases

Stereoselective methods for the synthesis of tetrahydro‐ß‐carbolines are of significant interest due to the broad spectrum of biological activity of the target molecules. In the plant kingdom, strictosidine synthases catalyze the C?C coupling through a Pictet–Spengler reaction of tryptamine and secologanin to exclusively form the (S)‐configured tetrahydro‐ß‐carboline (S)‐strictosidine. Investigating the biocatalytic Pictet–Spengler reaction of tryptamine with small‐molecular‐weight aliphatic aldehydes revealed that the strictosidine synthases give unexpectedly access to the (R)‐configured product. Developing an efficient expression method for the enzyme allowed the preparative transformation of various aldehydes, giving the products with up to >98 % ee. With this tool in hand, a chemoenzymatic two‐step synthesis of (R)‐harmicine was achieved, giving (R)‐harmicine in 67 % overall yield in optically pure form.     

Untersuchungen über die lösungsspektrochemische Silicatanalyse von Eisenerzen

An investigation on the spectral solution analysis of silicate in iron ores revealed that the decomposition by fusion at 900° C with NaOH/Na₂O₂ in a nickel crucible is the most suitable one. This method is applicable up to 20% of SiO₂ in iron ores. The decomposition and the dissolution of the melt requires strict adherence to the conditions described. The standard deviation is about 0.3%, about 70% of the total scattering being caused by the decomposition process.