Capillary electrophoretic approach to screen for enzyme inhibitors in natural extracts

This paper demonstrates development of electrophoretically mediated micro analysis (EMMA), for screening protein tyrosine phosphatase (PTP) inhibitors in natural extracts. It is demonstrated that capillary electrophoresis (CE) separation of the substrate and the product allows for using the assay in an on-column format to monitor the reaction without typically used fluorogenic substrates. Michaelis-Menten kinetics parameters calculated based on the EMMA results (Km = 1.2-1.5 microM) were in a good agreement (Km = 1.0-1.5 microM) obtained using an off-line CE functional assay (CE FA). EMMA of PTP titrated with different concentrations of ligand demonstrated the peak-shift phenomenon normally seen in affinity capillary electrophoresis. This feature of EMMA gives an indication of the binding affinity of the ligand in addition to its functional activity, providing another dimension in characterization of the protein-inhibitor interaction. It was demonstrated that simultaneous screening of the primary PTP target and a secondary, counter target (PTP-C) using the EMMA format can be used to prioritize hits based on their specificity.     

Synthesis of a new polyfluorinated vinylogue of tetrathiafulvalene through 1,3-dipolar cycloaddition of ethyl beta-bromoperfluorodithiocrotonate with dimethyl acetylenedicarboxylate

The ethyl ester of beta-bromoperfluorodithiocrotonic acid reacts with dimethyl acetylenedicarboxylate to give 1,4-difluoro-2,3-bis(trifluoromethyl)-but-2-ene-1,4-diylidene-2,2'-bis(4',5'-dicarbomethoxy-1',3'-dithiole) (4), a new type of vinylogue of tetrathiafulvalene. The thermal transformations of this compound lead, depending on the temperature, to the formation of the cyclization products: 11,14-difluoro-2,3,8,9-tetra(carbomethoxy)-12,13-bis(trifluoromethyl)-1,4,7,10-tetrathiadispiro[4.0.4.4]tetradeca-2,8,11,13-tetraene (8) or 5,8-difluoro-6,7-bis(trifluoromethyl)-2,3-bis(carboxymethyl)-1,4-benzodithiine (11).     

Hierarchical Order Parameters for Macromolecular Assembly Simulations I: Construction and Dynamical Properties of Order Parameters

Macromolecular assemblies often display a hierarchical organization of macromolecules or their sub-assemblies. To model this, we have formulated a space warping method that enables capturing overall macromolecular structure and dynamics via a set of coarse-grained order parameters (OPs). This article is the first of two describing the construction and computational implementation of an additional class of OPs that has built into them the hierarchical architecture of macromolecular assemblies. To accomplish this, first, the system is divided into subsystems, each of which is described via a representative set of OPs. Then, a global set of variables is constructed from these subsystem-centered OPs to capture overall system organization. Dynamical properties of the resulting OPs are compared to those of our previous nonhierarchical ones, and implied conceptual and computational advantages are discussed for a 100ns, 2 million atom solvated Human Papillomavirus-like particle simulation. In the second article, the hierarchical OPs are shown to enable a multiscale analysis that starts with the N-atom Liouville equation and yields rigorous Langevin equations of stochastic OP dynamics. The latter is demonstrated via a force-field based simulation algorithm that probes key structural transition pathways, simultaneously accounting for all-atom details and overall structure.     

Urease adsorption and activity on magnetite nanoparticles functionalized with monofunctional and bifunctional surface layers

The surface of magnetite nanoparticles was coated with functional polysiloxane layers using reaction of hydrolytic copolycondensation of tetraethoxysilane and 3-aminopropyltriethoxysilane (or N-[3-trimethoxysilylpropyl]ethylendiamine), and also that of tetraethoxysilane, 3-aminopropyltriethoxysilane and methyltriethoxysilane (or n-propyltriethoxysilane). It was shown that these functionalized magnetically controllable particles (about 60–150 nm in size as aggregates), as opposed to magnetite, adsorb urease well from aqueous solutions (up to 1 g/g), and that the level of residual activity of adsorbed layers is up to 84 % in the case of a bifunctional sample. It was established that the activity of immobilized urease is normally gradually reduced during storage of the samples, but in the case of ethylenediamine functional group is not decreased for 45 days. The synthesized samples are promising for use as magnetically directed biocatalysts.     

Sulfonimidamides and Imidosulfuric Diamides: Compounds from an Underexplored Part of Biologically Relevant Chemical Space

Two novel solid reagents—1-sulfonimidoyl- and 1-sulfamimidoyl-3-methylimidazolium derivatives—for the synthesis of sulfonimidamides and imidosulfuric diamides, respectively, were developed. It is shown that these reagents are very effective in substitution reactions with various N- and O-nucleophiles; therefore, they significantly extend the accessibility to the chemical space covered by organosulfur(VI) compounds with S=N bonds. In addition, previously unknown imidosulfuric diamides with free imino nitrogen groups were prepared, and their physical and chemical properties were characterized (including molecular geometry, pK_a, Log P, microsomal stability, and reactivity towards typical electrophiles). Similar to other organosulfur(VI) derivatives with S=N bonds, these compounds can be considered as promising bioisosteres of amides, ureas, or sulfonamides.     

Rational design of methacrylate monomers containing oxadiazole moieties for single‐layer organic light emitting devices

Methacrylate derived monomers functionalized with pendant oxadiazole moieties were synthesized and copolymerized with carbazole containing monomers to form polymers with electron and hole transporting fragments in the same molecule. Substituents on the oxidazole moiety were varied with the purpose of bandgap tuning and performance optimization when employed in single‐layer organic light emitting devices (OLED). Quantum mechanical calculations of the HOMO‐LUMO levels of the oxidazole derivatives were used to down‐select promising candidates for chemical synthesis and testing in single‐layer OLEDs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 1663–1673     

Hybrid silica-organic material with immobilized amino groups: surface probing and use for electrochemical determination of nitrite ions

A sol–gel based hybrid process was developed by manipulating different techniques in sol–gel process to synthesize γ-alumina and (CuO, CuO + ZnO) doped γ-alumina spherical particles. Catalysts having spherical geometry have an important advantage over powders or pellets which are impervious to fluids, when packed in a reactor. Boehmite sol was used as alumina precursor for synthesizing porous γ-alumina and doped materials. γ-alumina particles having 5 wt% CuO, 4 wt% CuO + 1 wt% ZnO, 3 wt% CuO + 2 wt% ZnO and 2 wt% CuO + 3 wt% ZnO were prepared by adding required amounts of Cu(NO₃)₂ and Zn(NO₃)₂ solutions prior to gelation of the sol. Methanol dehydration studies were carried out by employing these synthesized catalysts. Hundred percent conversion of methanol to dimethyl ether was observed with (4 wt% CuO + 1 wt% ZnO)-γ-alumina and (5 wt% CuO)-γ-alumina microspheres at 325 and 350 °C, respectively.     

Molecular Structure,Thermodynamic and Spectral Characteristics of Metal-Free and Nickel Complex of Tetrakis(1,2,5-thiadiazolo)porphyrazine

The Knudsen effusion method with mass spectrometric control of the vapor composition was used to study the possibility of a congruent transition to the gas phase and to estimate the enthalpy of sublimation of metal-free tetrakis(1,2,5-thiadiazolo)porphyrazine and its nickel complex (H₂TTDPz and NiTTDPz, respectively). The geometrical and electronic structure of H₂TTDPz and NiTTDPz in ground and low-lying excited electronic states were determined by DFT calculations. The electronic structure of NiTTDPz was studied by the complete active space (CASSCF) method, following accounting dynamic correlation by multiconfigurational quasi-degenerate second-order perturbation theory (MCQDPT2). A geometrical structure of D_2h and D_4h symmetry was obtained for H₂TTDPz and NiTTDPz, respectively. According to data obtained by the MCQDPT2 method, the nickel complex possesses the ground state ¹A_1g, and the wave function of the ground state has the form of a single determinant. Electronic absorption and vibrational (IR and resonance Raman) spectra of H₂TTDPz and NiTTDPz were studied experimentally and simulated theoretically.