Conjugation of nucleosides and oligonucleotides by [3+2] cycloaddition

A procedure is presented for copper(I)-catalyzed [3+2] cycloaddition of nucleosides and nucleotides in near-quantitative yield. Azido-alkyne cycloaddition was applied for the preparation of a range of adenosine dimers and derivatives with versatile functionality, as well as for the smooth condensation of two oligonucleotide strands. The described technology may find valuable application in the synthesis of oligonucleotide dimers and conjugates.     

Potentiometric DNA Sensor Based on Electropolymerized Phenothiazines for Protein Detection

Novel method of potentiometric detection of DNA‐protein interactions has been proposed. For this purpose, polymeric phenothiazine dyes, methylene blue (MB) and methylene green (MG), were electrochemically deposited onto the glassy carbon electrode and covered with double stranded DNA (dsDNA) as a target for antibodies (DNA‐sensor) or DNA aptamer specific to human α‐thrombin (aptasensor). The biosensors were consecutively incubated at pH 7.5 and 3.0 and the difference in potentials, ΔE, was used as a measure of protein concentration. The potentiometric DNA‐sensors were tested in standard serum of autoimmune disease patients (systemic lupus erythemathosus (SLE) and autoimmune thyroidites). It was shown, that the ΔE value of DNA‐sensor depends on the dilution of serum in the range from 1 : 1 to 1 : 100. Nonthermostated serum exhibited bell‐shape dependence of ΔE on serum dilution due to interfering effect of serine proteins at maximum dilution between 1 : 20 and 1 : 50. For SLE serum thermostated at 56 °C the ΔE linearly decreased as a function of serum dilution and reached saturation at dilution 1 : 20. Similarly the changes in the potential of aptasensor allowed us to determine the α‐thrombin in the range from 1 nM to 1 μM. The Faradic impedance spectra measured at presence of redox probe [Fe(CN)₆]^4?/3? revealed changes in the resistance and capacitance attributed to the shielding effect of anti‐DNA antibodies and an increase in the electron transfer. The developed potentiometric biosensors can be used for preliminary diagnostics of autoimmune diseases and thrombin detection with sensitivity comparable to traditional methods. The developed assay is, however simpler and cheaper in comparison with commonly used methods.     

Molecular structure and dynamics in the low temperature (orthorhombic) phase of NH3BH3

Variable temperature 2H NMR experiments on the orthorhombic phase of selectively deuterated NH3BH3 spanning the static to fast exchange limits of the borane and amine motions are reported. New values of the electric field gradient (EFG) tensor parameters have been obtained from the static 2H spectra of V(zz) = 1.652 (+/-0.082) x 10(21) V/m(2) and eta = 0.00 +/- 0.05 for the borane hydrogens and V(zz) = 2.883 (+/-0.144) x 10(21) V/m(2) and eta = 0.00 +/- 0.05 for the amine hydrogens. The molecular symmetry inferred from the observation of equal EFG tensors for the three borane hydrogens and likewise for the three amine hydrogens is in sharp contrast with the C(s) symmetry derived from diffraction studies. The origin of the apparent discrepancy has been investigated using molecular dynamics methods in combination with electronic structure calculations of NMR parameters, bond lengths, and bond angles. The computation of parameters from a statistical ensemble rather than from a single set of atomic Cartesian coordinates gives values that are in close quantitative agreement with the 2H NMR electric field gradient tensor measurements and are more consistent with the molecular symmetry revealed by the NMR spectra.     

Cerium(IV)-containing oxomolybdenum cluster with a unique Ce6Mo9O38 core structure

Interaction of [Ce(L(OEt))(2)(NO(3))(2)] (L(OEt)(-) = [Co(eta(5)-C(5)H(5)){P(O)(OEt)(2)}(3)](-)) with (NH(4))(6)[Mo(7)O(24)] in water affords the cerium(iv)-containing oxomolybdenum cluster [H(4)(CeL(OEt))(6)Mo(9)O(38)], which exhibits a unique Ce(6)Mo(9)O(38) core structure.     

[2+2+1+1] Cycloaddition for de novo Synthesis of Densely Functionalized Phenols

A unique benzannulation strategy for regioselective de novo synthesis of densely functionalized phenols is described. Through metal-mediated formal [2+2+1+1] cycloaddition of two different alkynes and two molecules of CO, a series of densely functionalized phenols were obtained. The benzannulation strategy allows efficient regioselective installation up to five different substituents on a phenol ring. The resulting phenols have a substitution pattern different from those obtained from Dötz and Danheiser benzannulations.     

Eigen kinetics in surface complexation of aqueous metal ions

The mechanism of chemisorption of aqueous metal ions at surfaces has long been a topical issue in such fields as soil chemistry and bioenvironmental science. Here it is quantitatively demonstrated for the first time that release of water from the inner hydration shell is the rate-limiting step in inner-sphere surface complexation. The reactive intermediate is an outer-sphere complex between metal ion and surface site, with an electrostatically controlled stability defined by Boltzmann statistics. Using tabulated dehydration rate constants for metal ions, the resulting scheme allows for prediction of rates of sorption of aqueous metal ions at any type of complexing surface.     

Steady-state diffusion regime in solid-phase microextraction kinetics

The temporal evolution of diffusion-controlled analyte accumulation in solid-phase microextraction (SPME) is critically discussed in terms of the various aspects of steady-state diffusion in the two phases under conditions of fast exchange of the analyte at the solid phase film/water interface. For partition coefficients (K_sw) much larger than unity and a sufficiently thin polymer film, the concentration gradient of the analyte in the polymer phase is largely insignificant. The growth of the accumulated amount of analyte is then adequately described by the well-known exponential expression for steady-state diffusion under non-depletive conditions, provided the initial transient stage is properly taken into account. In case of fiber-type solid phases, the cylindrical nature of the diffusion complicates the nature of the transient stage as well as the magnitude of the steady-state flux.     

Dielectric investigation of the liquid crystal compound with the directSmA*–SmCA* phase transition

New compound showing a direct SmA*–SmC_A* phase transition was synthesised. As far as authors know there are a few pure compounds showing para- and antiferroelectric phases without SmC* between them. Direct current (DC) field applied into a planar-oriented cell induces ferroelectric SmC* phase in an investigated compound. Typical for SmC*, Goldstone mode starts to be detectable. DC field also shifts down the temperature of a SmC_A* phase creation. Moreover, modes in the appearing antiferroelectic phase are enhanced by DC field. This paper shows and discusses relations between modes detected in SmA*, SmC_A* and SmC* (SmC* phase – nucleated by DC field) phases. Parameters of observed modes are calculated using the Cole–Cole relaxation model and a calculation procedure useful especially for high frequency relaxations (higher than 200 kHz).     

A Set of Activity‐Based Probes to Visualize Human (Immuno)proteasome Activities

Proteasomes are therapeutic targets for various cancers and autoimmune diseases. Constitutively expressed proteasomes have three active sites, β1c, β2c, and β5c. Lymphoid tissues also express the immunoproteasome subunits β1i, β2i, and β5i. Rapid and simultaneous measurement of the activity of these catalytic subunits would assist in the discovery of new inhibitors, improve analysis of proteasome inhibitors in clinical trials, and simplify analysis of subunit expression. In this work, we present a cocktail of activity‐based probes that enables simultaneous gel‐based detection of all six catalytic human proteasome subunits. We used this cocktail to develop specific inhibitors for β1c, β2c, β5c, and β2i, to compare the active‐site specificity of clinical proteasome inhibitors, and to demonstrate that many hematologic malignancies predominantly express immunoproteasomes. Furthermore, we show that selective and complete inhibition of β5i and β1i is cytotoxic to primary cells from acute lymphocytic leukemia (ALL) patients.     

Solid Separation from a Mixed Suspension through Electric‐Field‐Enhanced Crystallization

When applied to a pure component suspension in an apolar solvent, a strong inhomogeneous electric field induces particle movement, and the particles are collected at the surface of one of the two electrodes. This new phenomenon was used to separately isolate two organic crystalline compounds, phenazine and caffeine, from their suspension in 1,4‐dioxane. First, crystals of both compounds were collected at different electrodes under the influence of an electric field. Subsequent cooling crystallization enabled the immobilization and growth of the particles on the electrodes, which were separately collected after the experiment with purities greater than 91 %. This method can be further developed into a technique for crystal separation and recovery in complex multicomponent suspensions of industrial processes.