Effects of ligands on ion-pairing behavior of benzylic lithium compounds

The $\text{1}\text{1}$ adduct of t-butyllithium and α-methylstyrene (II) has been generated in cyclopentane in the presence of a variety of ether and t-amine ligands as well as unsolvated, giving stable solutions in every case. NMR spectra of the solvated species are the same for all ligands but differ from that of the unsolvated compound. The results are consistent with a salt which contains a conjugated t-benzylic anion and exists as a loose ion-pair in the presence of ligands and as a tight ion-pair in cyclopentane alone. In contrast, benzyllithium behaves like a tight ion-pair in the presence of all ligands tried. Steric hindrance to tight ion-pairing at C_α of II is concluded to be responsible for the results observed.A covalently-bonded dilithium compound, 4,4-dimethyl-2-lithio-2-(p-lithiophenyl)pentane has been generated.     

The Broad Aryl Acid Specificity of the Amide Bond Synthetase McbA Suggests Potential for the Biocatalytic Synthesis of Amides

Amide bond formation is one of the most important reactions in pharmaceutical synthetic chemistry. The development of sustainable methods for amide bond formation, including those that are catalyzed by enzymes, is therefore of significant interest. The ATP‐dependent amide bond synthetase (ABS) enzyme McbA, from Marinactinospora thermotolerans, catalyzes the formation of amides as part of the biosynthetic pathway towards the marinacarboline secondary metabolites. The reaction proceeds via an adenylate intermediate, with both adenylation and amidation steps catalyzed within one active site. In this study, McbA was applied to the synthesis of pharmaceutical‐type amides from a range of aryl carboxylic acids with partner amines provided at 1–5 molar equivalents. The structure of McbA revealed the structural determinants of aryl acid substrate tolerance and differences in conformation associated with the two half reactions catalyzed. The catalytic performance of McbA, coupled with the structure, suggest that this and other ABS enzymes may be engineered for applications in the sustainable synthesis of pharmaceutically relevant (chiral) amides.     

Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA

Trehalose is a nonreducing disaccharide that plays a major role in many organisms, most notably in survival and stress responses. In Mycobacterium tuberculosis, it plays a central role as the carbohydrate core of numerous immunogenic glycolipids including "cord factor" (trehalose 6,6'-dimycolate). The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA. The configurations of two anomeric positions are set simultaneously, resulting in the formation of a double glycoside. The three-dimensional structure of the Escherichia coli OtsA, in complex with both UDP and glucose-6-phosphate, reveals the active site at the interface of two beta/alpha/beta domains. The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism.     

Convective heat transfer and MHD effects on Casson nanofluid flow over a shrinking sheet

Current study examines the magnetohydrodynamic (MHD) boundary layer flow of a Casson nanofluid over an exponentially permeable shrinking sheet with convective boundary condition. Moreover, we have considered the suction/injection effects on the wall. By applying the appropriate transformations, system of non-linear partial differential equation along with the boundary conditions are transformed to couple non-linear ordinary differential equations. The resulting systems of non-linear ordinary differential equations are solved numerically using Runge-Kutta method. Numerical results for velocity, temperature and nanoparticle volume concentration are presented through graphs for various values of dimensionless parameters. Effects of parameters for heat transfer at wall and nanoparticle volume concentration are also presented through graphs and tables. At the end, fluid flow behavior is examined through stream lines. Concluding remarks are provided for the whole analysis.     

Subspaces of L p that embed into L p (µ) with µ finite

Enflo and Rosenthal [4] proved that ? _p (?₁), 1 < p < 2, does not (isomorphically) embed into L _p (µ) with µ a finite measure. We prove that if X is a subspace of an L _p space, 1 < p < 2, and ? _p (?₁) does not embed into X, then X embeds into L _p (µ) for some finite measure µ.     

Thermal degradation of poly(acrylic acid) containing metal nitrates and the formation of YBa2Cu3O7−x

The use of polymers containing metal salts as ceramic high‐temperature superconductor (HTSC) precursors may provide a relatively simple and rapid method for producing materials that can take advantage of advanced polymer processing and then be pyrolyzed to HTSCs. The mechanisms of thermal degradation in these precursors, which have not been characterized, can be used to optimize the pyrolysis conditions for HTSC production. This article describes the degradation of a precursor based on poly(acrylic acid) (PAAc) containing yttrium, barium, and copper nitrates in the proportions needed for the formation of the HTSC YBa₂Cu₃O_7?x (YBCO). This article also describes the effects of the pyrolysis process on the resulting materials. The degradation of the precursor is a complex, multistage process. The presence of the metal ions and HNO₃ reduces the thermal stability of PAAc and increases the degradation rate. The results indicate that the initial stages of the pyrolysis should be conducted in argon or nitrogen to inhibit BaCO₃ formation and that the final stages should be conducted in air/oxygen to enhance oxidation. Optimization of the pyrolysis conditions produces a YBCO film with minimal contamination. © 2005 Wiley Periodicals, Inc. J PolymSci Part B: Polym Phys 43: 1168–1176, 2005     

Combined Inhibitor Free‐Energy Landscape and Structural Analysis Reports on the Mannosidase Conformational Coordinate

Mannosidases catalyze the hydrolysis of a diverse range of polysaccharides and glycoconjugates, and the various sequence‐based mannosidase families have evolved ingenious strategies to overcome the stereoelectronic challenges of mannoside chemistry. Using a combination of computational chemistry, inhibitor design and synthesis, and X‐ray crystallography of inhibitor/enzyme complexes, it is demonstrated that mannoimidazole‐type inhibitors are energetically poised to report faithfully on mannosidase transition‐state conformation, and provide direct evidence for the conformational itinerary used by diverse mannosidases, including β‐mannanases from families GH26 and GH113. Isofagomine‐type inhibitors are poor mimics of transition‐state conformation, owing to the high energy barriers that must be crossed to attain mechanistically relevant conformations, however, these sugar‐shaped heterocycles allow the acquisition of ternary complexes that span the active site, thus providing valuable insight into active‐site residues involved in substrate recognition.     

Discovery of Selective Small‐Molecule Activators of a Bacterial Glycoside Hydrolase

Fragment‐based approaches are used routinely to discover enzyme inhibitors as cellular tools and potential therapeutic agents. There have been few reports, however, of the discovery of small‐molecule enzyme activators. Herein, we describe the discovery and characterization of small‐molecule activators of a glycoside hydrolase (a bacterial O‐GlcNAc hydrolase). A ligand‐observed NMR screen of a library of commercially available fragments identified an enzyme activator which yielded an approximate 90 % increase in k_cat/K_M values (k_cat=catalytic rate constant; K_M=Michaelis constant). This compound binds to the enzyme in close proximity to the catalytic center. Evolution of the initial hits led to improved compounds that behave as nonessential activators effecting both K_M and V_max values (V_max=maximum rate of reaction). The compounds appear to stabilize an active “closed” form of the enzyme. Such activators could offer an orthogonal alternative to enzyme inhibitors for perturbation of enzyme activity in vivo, and could also be used for glycoside hydrolase activation in many industrial processes.