Trifluoromethanesulfonyl azide: an efficient reagent for the preparation of α-cyano-α-diazo carbonyls and an α-sulfonyl-α-diazo carbonyl

The reaction scope of trifluoromethanesulfonyl azide in diazo transfer reactions was extended to include the preparation of α-cyano-α-diazo-carbonyls, phenyl sulfonyl diazoacetophenone and diethyl diazomalonate in high yields. The effect of the bases used in the diazo transfer reactions were found to have a dramatic influence on the success of the reaction with pyridine being the base of choice.     

Ruthenium-catalyzed [2+2] cycloadditions between C1-substituted 7-oxanorbornadienes and alkynes

Ruthenium-catalyzed [2+2] cycloadditions between C1-substituted 7-oxanorbornadienes and alkynes were investigated. Most of the cycloadditions occurred smoothly at 65 °C, giving the cyclobutene cycloadducts in moderate to good yields. The C1 substituent showed strong effect on the regioselectivity (up to 110:1) of the cycloadditions.     

Vacuum ultraviolet spark emission spectra of fluorine and some polyatomic fluorides in noble gases

Spark emission spectra in the vacuum ultraviolet are reported for several polyatomic fluorides in He + Ar mixtures, and for pure fluorine. These results are discussed in terms of the potential of a given fluorine compound for ArF formation. The 158 nm emission in fluorine is tentatively assigned to the ³Π_g → ³Π_u.     

The HLB dependency for detergent solubilization of hormonally sensitive adenylate cyclase.

The HLB dependency for the solubilization of membrane proteins and adenylate cyclase activity from a plasma membrane-enriched fraction from rat liver has been determined. The HLB (hydrophilic/lipophilic/balance) number of a detergent is an empirical measure of its relative hydrophobicity. Detergent HLB numbers vary systematically with the length of the ethylene oxide chain for a homologous series of detergents such as the Triton X series. These detergents have a constant hydrophobic moiety, octylphenyl, and a variable polar portion, polyethoxyethanol. Basal-NaF-epinephrine-, and glucagon-stimulated adenylate cyclase activities were solubilized in the HLB range of 16.8-17.4. Solubilization was most effective in 0.01 M Tris buffers at pH 7.5 containing 1-5 mM mercaptoethanol, 1 mM MgCl2, and 0.1% Triton X-305. The detergent to membrane protein ratio used in these studies was 3:1. Criteria for solubilization included lack of sedimentation at 100,000 X g, the absence of particulate material in the supernatant when examined by electron microscopy, and inclusion of hormonally sensitive adenylate cyclase activity in Sephadex G-200 gels. The apparent molecular weight of the solubilized enzyme was approximately 200,000 in the presence of Triton X-305. The solubilized enzyme was stimulated 5-fold by NaF, 7-fold by glucagon, and 20-fold by epinephrine compared to the particulate enzyme used in this study which was stimulated 10-fold, 3.4-fold, and 4-fold by NaF, epinephrine, and glucagon, respectively. The solubilized enzyme is stable for several weeks when stored at -60 degrees C.     

Identification of novel macrocyclic peptidase substrates via on-bead enzymatic cyclization

Peptidase-catalyzed formation of macrocyclic lactams on solid phase identifies ring systems that are favorably bound in the enzyme active site. We evaluated several cyclic peptide motifs linked by ester bonds between the P2 and P1' or the P1 and P2' side chains. The depsipeptide represented by structure 5 was readily generated by a variety of peptidases from precursor omega-amino acids or omega-amino esters. This strategy for identifying ring systems for potential macrocyclic transition state analogues was demonstrated with the serine peptidases trypsin and chymotrypsin, with the aspartic peptidase pepsin, and with the zinc peptidase thermolysin.     

An in situ atomic force microscopy study of uric acid crystal growth

Kidney stones are heterogeneous polycrystalline aggregates that can consist of several different building blocks. A significant number of human stones contain uric acid crystals as a crystalline component, though the molecular-level growth of this important biomaterial has not been previously well-characterized. In the present study, in situ atomic force microscopy (AFM) is used to investigate the real-time growth on the (100) surface of uric acid (UA) single crystals as a function of fundamental solution parameters. Layer-by-layer growth on UA (100) was found to be initiated at screw dislocation sites and to proceed via highly anisotropic rates which depend on the crystallographic direction. The smallest b-steps exhibited minimum heights corresponding to two molecular layers, while fast-moving c-steps more commonly showed monolayer heights. Growth kinetics measured under a range of flow rates, supersaturation levels, and pH values reveal linear trends in the growth kinetics, with faster growth attained in solutions with higher supersaturation and/or pH. The calculated kinetic parameters for UA growth derived from these experiments are in good agreement with the values reported for other crystal systems.     

Microfabrication of three-dimensional bioelectronic architectures

The functionality and structural diversity of biological macromolecules has motivated efforts to exploit proteins and DNA as templates for synthesis of electronic architectures. Although such materials offer promise for numerous applications in the fabrication of cellular interfaces, biosensors, and nanoelectronics, identification of techniques for positioning and ordering bioelectronic components into useful patterns capable of sophisticated function has presented a major challenge. Here, we describe the fabrication of electronic materials using biomolecular scaffolds that can be constructed with precisely defined topographies. In this approach, a tightly focused pulsed laser beam capable of promoting protein photo-cross-linking in specified femtoliter volume elements is scanned within a protein solution, creating biomolecular matrices that either remain in integral contact with a support surface or extend as free-standing structures through solution, tethered at their ends. Once fabricated, specific protein scaffolds can be selectively metallized via targeted deposition and growth of metal nanoparticles, yielding high-conductivity bioelectronic materials. This aqueous fabrication strategy opens new opportunities for creating electronic materials in chemically sensitive environments and may offer a general approach for creating microscopically defined inorganic landscapes.     

Comparison of the electrophilic and free-radical addition of halogens with hexafluoro-1,3-butadiene and 1,3-butadiene

Ionic and photochemical reaction of chlorine (Cl₂), bromine (Br₂) and iodine monochloride (ICl) to hexafluoro-1,3-butadiene (1) and 1,3-butadiene (2) were carried out under conditions that would provide product distributions under controlled ionic or free-radical conditions. Product distributions for ionic reaction of Cl₂ and Br₂ with 1 are similar and suggest a weakly-bridged halonium ion species. Theoretical calculations support weakly-bridged chloronium and bromonium ions for both dienes 1 and 2. There are more of the 1,4-dihalo-2-butene products from ionic halogenation of 1 than 2 which correlates with the greater charge density on carbon-4 of halonium ions from 1. Ionic and free-radical reactions of ICl with 1 give 8 and 2% of 3-chloro-4-iodohexafluoro-1-butene and 4-chloro-3-iodohexafluoro-1-butene, respectively. The minor cis-1,4-dihalo-2-butene products from 1 and 2 are reported when formed.     

Transferable atom equivalent multicentered multipole expansion method

The transferability of atomic and functional group properties is an implicit concept in chemistry. The work presented here describes the use of Transferable Atom Equivalents (TAE) to represent molecular electrostatic potential fields through the use of integrated atomic multipole moments that are associated with each TAE atom type used in the reconstruction. TAE molecular surface distributions of electrostatic potentials are compared with analytical ab initio and empirical (Gasteiger) partial charge reference models for several conformations of test peptides. Surface electrostatic potential distributions computed using TAE multipole representations were found to converge at the octopole level, with incremental improvement observed when hexadecapoles were included. Molecular electrostatic potential fields that were produced using the TAE method were observed to be responsive to conformational changes and to compare well with ab initio reference distributions. Generation of TAE atom types and their associated multipoles does not involve fitting to sample electrostatic potential fields, but rather utilizes integrated AIM atomic electron density distributions within representative chemical environments. The RECON program was used for TAE reconstruction. RECON is capable of processing 5,000 drug-sized molecules or 25 proteins per minute per 1.7 GHz P4 Linux processor.     

Field gradient electrophoresis

The class of equilibrium gradient methods utilizes the opposition of two forces, at least one of which changes in magnitude with position, to separate and concentrate analytes. The drawback of many methods of this type is that the production of two opposing forces requires in comparison to standard methods, such as capillary electrophoresis, a relatively complex apparatus. In addition, for techniques such as electric field gradient focusing, hydrodynamic flow leads to Taylor dispersion, which limits the attainable concentration factor. We propose a new method, gradient field electrophoresis, which achieves analyte separation and focusing with only one spatially varying force, an electric field gradient. A model for the method is developed and used to analyze peak capacity. Experimental results for a protein (R-phycoerythrin) are given and compared to the model.