N-shaped organic semiconductors are synthesized via four steps from a readily available starting material. Such semiconductors exhibit preferable ionization potential for p-type operation, thermally stable crystalline phase over 200 °C, and high carrier mobility up to 16 cm(2) V(-1) s(-1) (12.1 cm(2) V(-1) s(-1) on average) with small threshold voltages in solution-crystallized field-effect transistors.

V-shaped organic semiconductors have been designed and synthesized via a large-scale applicable synthetic route. Solution-crystallized films based on such molecules have demonstrated high-performance transistor properties with maximum mobilities of up to 9.5 cm(2) V(-1) s(-1) as well as pronounced thermal durability of up to 150 °C inherent in the V-shaped cores.

The botulinum neurotoxins (BoNTs) are the most potent toxins known in nature, causing the lethal disease known as botulism in humans and animals. The BoNTs act by inhibiting neurotransmitter release from cholinergic synapses. Clostridium botulinum strains produce large BoNTs toxin complexes, which include auxiliary non-toxic proteins that appear not only to protect BoNTs from the hostile environment of the digestive tract but also to assist BoNT translocation across the intestinal mucosal layer. In this study, we visualize for the first time a series of botulinum serotype D toxin complexes using negative stain transmission electron microscopy (TEM). The complexes consist of the 150-kDa BoNT, 130-kDa nontoxic non-hemagglutinin (NTNHA), and three kinds of hemagglutinin (HA) subcomponents: 70-kDa HA-70, 33-kDa HA-33, and 17-kDa HA-17. These components assemble sequentially to form the complex. A novel TEM image of the mature L-TC revealed an ellipsoidal-shaped structure with "three arms" attached. The "body" section was comprised of a single BoNT, a single NTNHA and three HA-70 molecules. The arm section consisted of a complex of HA-33 and HA-17 molecules. We determined the x-ray crystal structure of the complex formed by two HA-33 plus one HA-17. On the basis of the TEM image and biochemical results, we propose a novel 14-mer subunit model for the botulinum toxin complex. This unique model suggests how non-toxic components make up a "delivery vehicle" for BoNT.Different strains of Clostridium botulinum produce seven distinct serotypes of neurotoxins (BoNTs), 2 classified A through G. BoNT has attracted much interest in recent years due to extensive research on its biochemistry, determination of its crystal structure, and investigations into the pharmacology and applications of BoNTs as therapeutic agents for the treatment of human disease (1-3). After ingestion of BoNT, the BoNT is absorbed from intestinal epithelial cells into the bloodstream, after which it consequently reaches the neuromuscular junctions. BoNT enters nerve cells via receptor-mediated endocytosis, where it cleaves specific sites on target proteins, inhibiting release of neurotransmitters from peripheral cholinergic synapses through its zinc protease activity (4 -6). This process causes muscular paralysis in humans and animals, leading to the disease botulism.Toxins with serotypes A-D and G are encoded by two gene clusters in close proximity to each other; cluster 1 contains the bont and ntnha genes, and cluster 2 contains three genes : ha-70, ha-33, and ha-17 (7, 8). Therefore, botulinum TC consists of five components: BoNT, non-toxic non-hemagglutinin (NTNHA) and three hemagglutinin subcomponents (HA-70, HA-33, and HA-17). All serotypes of BoNT associate non-covalently with auxiliary non-toxic proteins, thereby forming large toxin complexes (TCs). Serotype A-D strains produce the M-TC (BoNT⅐NTNHA complex) and L-TC (BoNT⅐NTNHA⅐HAs complex) in the culture medium, while serotype E and F strains produce only M-TC. The major biological function of t...

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We show through hen egg-white lysozyme nucleation experiments under light produced by a 300 W continuous Xe lamp that nucleation is enhanced. The irradiation of supersaturated protein solutions in NaCl at pH 4.5, β ) 9, from 10 to 60 s increased the number of lysozyme crystals in the droplet. The most effective irradiation time is from 10 to 30 s, and in this range, enzyme activity is not affected. The resulting crystal lattice parameters are identical to that normally obtained. We propose the following mechanism: intermediates produced by one photon absorption produce lysozyme radicals, which enhance nucleation. These results suggest a new method for controlling nucleation and growth that could be used in structural genomics and the pharmaceutical industry, for instance.

Motion correlated over 5-8 Å (liquid-like movement) has been shown by the non-Bragg technique of x-ray diffuse scattering to be important in insulin and lysozyme crystals (1, 2). State of the art molecular dynamics methods cannot model such correlations (3), perhaps because of inadequate sampling of conformational substates (4). Multiple substates of nearly equal energy are also proposed for myoglobin based on spectroscopic evidence (5-7), but spectroscopy is not well suited to elucidate the nature of these substates. Neither is NMR, unless extremely tight distance restraints are used (8).Diffraction from a crystal is averaged over many unit cells and over the time spent on data collection. It is generally believed that this averaging precludes extracting dynamic information, such as occurrence of multiple substate correlations from an x-ray structure. However, nonrandom correlations will contribute to Bragg reflections. Given diffraction data beyond 1.4 Å (9), the correlations can be modeled as substate disorder and provide insight into protein dynamics. If one could physically separate the substates and study each separately, one could prove such correlations exist and derive the rules for the correlation.Crambin presents an excellent system for such an experiment. Crambin from the natural source contains two sequence isomers in a 3:2 ratio (10, 11), the so-called mixed form of crambin. The major isomer has Pro and Leu at positions 22 and 25, respectively (the PL form); 1 the minor isomer has Ser and Ile at the same positions (the SI form). In the mixed form crystal structure, side chain electron densities for heterogeneous residues are superimposed (Pro and Ser at residue 22 and Leu and Ile at residue 25). The Tyr-29 side chain from a 2 1 -screw axis-related molecule has close contacts with the Pro or Ser residue and adopts two conformations. A proposed correlation of the Tyr-29 conformation with the identity of the amino acid at residue 22 (12) has been supported by the PL form structure (13). Now the second or SI form of crambin has been purified by fast protein liquid chromatography and crystallized. It establishes the side chain correlations definitively and establishes associated solvent interactions.In this paper, first the proposed mixed form protein networks are extended to water disorder using stereochemical "rules," such as van der Waals' contacts and hydrogen bonding. Second, these postulated networks are compared with the crystal structures of the physically separated pure forms of crambin: the PL form structure and the newly determined SI form structure. These results establish that the x-ray structure of the mixed form of crambin can elucidate substate spatial correlations between side chains and solvent, as proven by the pure form structures.Alternative conformations at disordered residues and water molecules are designated by attaching A and B to the residue number. Such disordered conformations are often correlated with neighboring residue disorder through space and may represent conformation...

Two birds, one stone! The first kinetic resolution of allyl fluorides was achieved by the development of an organocatalyzed enantioselective allylic trifluoromethylation. Two kinds of chiral fluorinated compounds, which incorporate C*F and C*CF3 units, respectively, can thus be accessed by a single transformation.