Influence of Steric Effect on the Pseudo-Multicomponent Synthesis of N-Aroylmethyl-4-Arylimidazoles

A pseudo-three-component synthesis of N-aroylmethylimidazoles 3 with three new C–N bonds formed regioselectively under microwave conditions was developed. Products were obtained by reacting two equivalents of aroylmethyl bromide (ArCOCH₂Br, 1) with the appropriate amidine salt (RCN₂H₃.HX, 2) and with K₂CO₃ as a base in acetonitrile. The bicomponent reaction also occurred, giving the expected 4(5)-aryl-1H-imidazoles 4. Notably, the ratio of products 3 and 4 is governed by steric factors of the amidine 2 (i.e., R = H, CH₃, Ph). Therefore, a computational study was carried out to understand the reaction course regarding product ratio (3/4), regioselectivity, and the steric effects of the amidine substituent group.     

Studies directed toward the fabrication of a synthetic cation-conducting channel based on lariat ethers: The feeble forces concept for self-assembly

The work described here derives from our observation that while Nature certainly utilizes covalent interactions and other forces of great strength in the construction of biomolecules, many feeble forces are involved as well. We have used feeble forces in model studies directed eventually to the synthesis of a self-assembling, cation-conducting channel. Specifically, we have prepared three models for portions of such a cation-conducting channel. The first is based on the steroidal lariat ethers that clearly self-assemble. This process involvesinter alia entropy as a feeble force of cumulative importance. Second, we have prepared threetris(macrocyclic) systems that are simplified versions of the proposed channel-former. Third, we have demonstrated the strength of carefully-conceived hydrogen bonding interactions by constructing a molecular box based on the interaction between adenine and thymine.     

Anomalous structural dynamics of minimally frustrated residues in cardiac troponin C triggers hypertrophic cardiomyopathy

Cardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca²⁺-regulation of myocardial contraction. Here, we report the molecular basis of a human mutation in cTnC''s αD-helix (TNNC1-p.C84Y) that impacts conformational dynamics of the D/E central-linker and sampling of discrete states in the N-domain, favoring the “primed” state associated with Ca²⁺ binding. We demonstrate cTnC''s αD-helix normally functions as a central hub that controls minimally frustrated interactions, maintaining evolutionarily conserved rigidity of the N-domain. αD-helix perturbation remotely alters conformational dynamics of the N-domain, compromising its structural rigidity. Transgenic mice carrying this cTnC mutation exhibit altered dynamics of sarcomere function and hypertrophic cardiomyopathy. Together, our data suggest that disruption of evolutionary conserved molecular frustration networks by a myofilament protein mutation may ultimately compromise contractile performance and trigger hypertrophic cardiomyopathy.

Cardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca²⁺-regulation of myocardial contraction.     

Interplay of orbital symmetry and nonstatistical dynamics in the thermal rearrangements of bicyclo[n.1.0]polyenes.

CASSCF and CASPT2 calculations have been carried out on some of the thermal rearrangements of bicyclo[2.1.0]pentene (BCP), bicyclo[4.1.0]hepta-2,4-diene (BCH), bicyclo[6.1.0]nona-2,4,6-triene (BCN), and 9,9-dicyanobicyclo[6.1.0]nona-2,4,6-triene (DCBCN). In addition, experiments have been conducted to determine the stereoselectivity and temperature dependence of the nondegenerate rearrangement of 9,9-dicyanobicyclo[6.1.0]nona-2,4,6-triene-exo-15N. The calculations and experiments allow a consistent picture to be drawn for these reactions. The principal conclusions are as follows. (1) The ring-walk rearrangements of BCP, BCN, and DCBCN are pericyclic reactions occurring with a strong preference for inversion of configuration at the migrating carbon. However, the ring-walk rearrangement of BCH is a nonpericyclic reaction. (2) The rearrangement of DCBCN to 9,9-dicyanobicyclo[4.2.1]nona-2,4,7-triene occurs with a preferred stereochemistry corresponding to a 1,3 migration with retention. However, this reaction is not a pericyclic process; the stereoselectivity is probably of dynamic origin. (3) Cyano substituents can significantly reduce the activation energy for a reaction occurring via a singlet biradical, but they do not necessarily cause the intermediate to sit in a deeper local minimum on the potential energy surface.     

1H and 13C NMR spectral assignment of androstane derivatives

(1)H and (13)C NMR spectroscopic data for 5alpha-androstanes and halo-5alpha-androstanes with different substituents at positions C-3, C-9, C-11 and C-17 were examined and assigned by a combination of 1D and 2D NMR experiments. The substituent effects on the (13)C chemical shifts were compared with those of epi-androsterone, used as a reference compound. The coupling constants (n)J((19)F,(13)C) were measured for compounds 6, 8, 11 and 14.     

The McMaster University Nuclear Reactor (MNR) research facilities

The McMaster University Nuclear Reactor (MNR) is a unique Canadian facility in a university environment welcoming researchers from across Canada and abroad. The irradiation and analytical facilities available cover a broad spectrum of nuclear analytical techniques from standard INAA to fully automated counting systems for prompt gamma activation analysis and delayed neutron counting. In addition, neutron beams provide for a wide spectrum of applied and basic nuclear research applications. This paper describes the state-of-the-art facilities available at McMaster.     

Fabrication of Low-cost Screen-printed Electrode in Paper Using Conductive Inks of Graphite and Silver/Silver Chloride

The fabrication of the Screen-Printed Electrode (SPE) was performed using the graphite ink to print the working (WE) and counter electrodes (CE), and silver/silver chloride path as reference electrode (RE). All the electrodes are printed in a paper substrate using screen-printing technique. The resulting SPE is characterized using scanning electron microscopy, showing all the ink layer, and subsequently optimized. The paper sample presented the cellulose fibers entanglement, extremely rough, with highly porous network. Then the graphite ink was deposited and the surface became flat, thinner and very smooth. When the silver ink was painted on top of the graphite ink, the spherical silver particles, ranged from 2–3.5 μm in size, were observed. And finally, the silver ink was covered with a AgCl layer and the particle size becomes larger with an irregular sphere-like phase. The images showed that the layers appear to be homogeneously distributed with good coverage. Then fabrication process was optimized concerning type of paper, the sanding process, the hydrophobic barrier, the electrode design and size. In summary, the optimized values included using the previously sanded matte paper with a mineral spirit layer. The design and size of the electrode were also tested to achieve the best electrochemical performance (design 3 with 3.5 cm). The final SPE was a miniaturized and flexible paper-based electrochemical electrode. In order to evaluate the electrical properties, the ohmic resistance of each ink was tested using a multimeter and the obtained values were 2.18 kΩ for the graphite ink, 2.27 Ω for the silver ink and 38.33 kΩ for the silver/silver chloride ink. That can indicate the good conductivity of each ink used in the fabrication of the electrode and the correct deposition of Ag/AgCl. Finally, the electrode was used to measure the electrochemical response of K₄[Fe(CN)₆] in different concentrations. Then a calibration curve was obtained from the voltammograms and a linearity was observed between the current and concentration in the range of 0.50–2.00 mM. That indicates that the SPE has potential to be used as a voltammetric electrode.     

Fluorescence based fiber optic and planar waveguide biosensors. A review

The application of optical biosensors, specifically those that use optical fibers and planar waveguides, has escalated throughout the years in many fields, including environmental analysis, food safety and clinical diagnosis. Fluorescence is, without doubt, the most popular transducer signal used in these devices because of its higher selectivity and sensitivity, but most of all due to its wide versatility. This paper focuses on the working principles and configurations of fluorescence-based fiber optic and planar waveguide biosensors and will review biological recognition elements, sensing schemes, as well as some major and recent applications, published in the last ten years. The main goal is to provide the reader a general overview of a field that requires the joint collaboration of researchers of many different areas, including chemistry, physics, biology, engineering, and material science.     

Assessment of Different Regeneration and Washing Solutions in an Affinity Chromatography Procedure to Purify Plantibodies

Purification efficiency is a great challenge in plantibody production. Several regeneration?+?washing solutions of ProSep^?-vA Ultra matrix used in plantibody HB-01 purification were assessed in this study to increase matrix stability without affecting purity and to reduce costs. In conclusion, PHB-01 purity was always higher than 90%. Citric acid (100?mM); pH 3.0/0.1% Triton X-100?+?150?mM PBS; pH 8.0 and 250?mM phosphoric acid; pH 1.5?+?150?mM PBS; pH 8.0/0.1% Triton X-100 allowed increasing purification cycles up to 60 and antibody yield 1.4 and 1.3 fold, respectively, together with a significant reduction in plantibody purification cost.     

Self-supported bacterial cellulose polyaniline conducting membrane as electromagnetic interference shielding material: effect of the oxidizing agent

Conducting bacterial cellulose (BC) membranes coated with a high proportion of polyaniline (PAni) were prepared through in situ oxidative polymerization of aniline on the surface of the BC in the presence of acetic acid as the protonating agent. The effect of two different oxidizing agents, ammonium persulfate (APS) or iron(III) chloride (FeCl₃), on the mechanical performance, electrical conductivity, crystallinity, morphology and ability to absorb the electromagnetic radiation was investigated. BC/PAni membranes prepared with FeCl₃ displayed higher conductivity and better mechanical performance than those observed for pure BC or the BC/PAni membranes prepared with APS. Experiments related to the electromagnetic absorbing properties revealed that BC/PAni membranes prepared with FeCl₃ also present improved absorbing properties in the frequency range of 8–12 GHz. The morphology of the membranes, observed by field emission gun-scanning electron microscopy, is strongly affected by the oxidizing agent. Whereas the BC/PAni membranes prepared with APS present PAni nanoparticles attached on the fiber surface as agglomerates in the form of flakes, those prepared with FeCl₃ display a uniform and smooth coating of PAni on the BC fibers as hierarchical mode.