Crystal structure,conformation and vibrational characteristics of diethyl 4,4′-disulfanediylbis(6-methyl-2-phenylpyrimidine-5-carboxylate) – A new pharmaceutical cure

The crystal and molecular structures of diethyl 4,4′-disulfanediylbis(6-methyl-2-phenylpyrimidine-5-carboxylate) have been determined by X-ray diffraction and quantum chemical DFT analysis. The title compound crystallizes in orthorhombic Pbca (D_2h¹⁵) space group, with one molecule in the asymmetric unit. The molecular structure of the studied compound has been determined using the DFT B3LYP/6-311G(2d,2p) approach and compared to that derived from X-ray studies. The IR and Raman spectra have been measured and their wavenumbers have been compared to those calculated for the optimized geometry of the studied compound. The characteristic vibrations of the 4,4′-dithiobispyrimidine N₂C₄SSC₄N₂ skeleton have been identified and on this basis the correlation between the disulfide bridge conformation and vibrational data have been discussed.     

Anion of the formic acid dimer as a model for intermolecular proton transfer induced by a pi* excess electron

The neutral and anionic formic acid dimers have been studied at the second-order Moller-Plesset and coupled-cluster level of theory with single, double, and perturbative triple excitations with augmented, correlation-consistent basis sets of double- and triple-zeta quality. Scans of the potential-energy surface for the anion were performed at the density-functional level of theory with a hybrid B3LYP functional and a high-quality basis set. Our main finding is that the formic acid dimer is susceptible to intermolecular proton transfer upon an excess electron attachment. The unpaired electron occupies a pi(*) orbital, the molecular moiety that accommodates an excess electron "buckles," and a proton is transferred to the unit where the excess electron is localized. As a consequence of these geometrical transformations, the electron vertical detachment energy becomes substantial, 2.35 eV. The anion is barely adiabatically unstable with respect to the neutral at 0 K. However, at standard conditions and in terms of Gibbs free energy, the anion is more stable than the neutral by +37 meV. The neutral and anionic dimers display different IR characteristics. In summary, the formic acid dimer can exist in two quasidegenerate states (neutral and anionic), which can be viewed as "zero" and "one" in the binary system. These two states are switchable and distinguishable.     

Limit theorems for hybridization reactions on oligonucleotide microarrays

We derive herein the limiting laws for certain stationary distributions of birth-and-death processes related to the classical model of chemical adsorption-desorption reactions due to Langmuir. The model has been recently considered in the context of a hybridization reaction on an oligonucleotide DNA-microarray. Our results imply that the truncated-gamma- and beta-type distributions can be used as approximations to the observed distributions of the fluorescence readings of the oligo-probes on a microarray. These findings might be useful in developing new model-based, probe-specific methods of extracting target concentrations from array fluorescence readings.     

Dirichlet problem for semilinear hyperbolic equation. Multidimensional case

We discuss the solvability of the Dirichlet problem for the semilinear equation of the vibrating string xtt(t,y)−Δx(t,y)+f(t,y,x(t,y))=0 in higher dimensions with sides length being irrational numbers and superlinear nonlinearity. To this effect we derive a new dual variational method.     

Stability and free vibrations of discrete frame subjected to the generalised load by the force directed towards the positive pole

The work refers to stability and free vibrations of discrete, two-part planar frame with three degree of freedom. For the considered frame the total mechanical energy is determined on the basis of the external load of the structure, whose direction of action depends on geometry of loading and receiving head. Adequate relationships describing stability of the considered frame are obtained taking into account potential energy of the system (static criterion) or total mechanical energy (kinetic criterion). An influence of geometrical parameters of loading head and rigidity of rotational springs modelling the finite stiffness of structural constraints on the critical load is analyzed. The courses of natural vibration frequencies in relation to the external loads are determined for the assumed values regarding geometry and physical constants of the system. (© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Sensitive Simultaneous Determination of Rutin and Folic Acid with the Use of a Solid Lead Electrode by Means of Adsorptive Stripping Voltammetry

In this article a solid lead electrode (PbE) was utilized for the first time for determination of organic substances by means of adsorptive stripping voltammetry. A new procedure of simultaneous determination of rutin and folic acid was developed. Two well shaped and well separated reduction signals of rutin and folic acid were obtained with the use of PbE. The optimization of analytical procedure was presented. The calibration graphs for rutin and folic acid for an accumulation time of 120 s were linear in the ranges from 2×10^?9 to 1×10^?7 mol L^?1 and from 2×10^?9 to 5×10^?8 mol L^?1, respectively. The obtained detection limits for rutin and folic acid determination following accumulation time of 120 s were 7.9×10^?10 and 8.4×10^?10 mol L^?1. Potential interference effects were investigated. The proposed procedure was used for analysis of pharmaceutical preparations with satisfactory results showing practical applications. The analytical parameters of the proposed procedure were compared with other voltammetric procedures of mentioned substances determination.     

Fast analysis of 19 anabolic steroids in bovine tissues by high performance liquid chromatography with tandem mass spectrometry

For the detection of 19 steroid hormones in bovine muscle, a fast and sensitive liquid chromatography with electrospray ionization tandem mass spectrometry method was developed using both positive and negative ionization mode. Chromatographic separation on Poroshell 120‐EC C18 column was achieved in less than 10 min using isocratic elution of mobile phase of acetonitrile/methanol/water. The compounds were extracted from muscle tissue using ethyl acetate and quick, easy, cheap, effective, rugged, and safe technique. The purification of the obtained extract was performed by dispersive solid‐phase extraction with sorbents C18, primary secondary amine and magnesium sulphate. The method was validated in accordance with the Commission Decision 2002/657/EC. For all steroids tested good recoveries were obtained (from 51.2 to 121.4%) in the concentration range from decision limits until 5 µg/kg. The values of decision limits and the detection capabilities for individual compounds were in the range 0.10–0.48 and 0.17–0.95 µg/kg, respectively. The method was characterized by satisfactory linearity for most compounds (correlation coefficients  > 0.99) and the reproducibility was lower than 35%. The elaborated procedure has met the criteria for confirmatory methods and is currently used in the official control of hormones.     

Total synthesis of reblastatin

Enantioselective total synthesis of reblastatin is described. The synthesis highlights hydrozirconation, transmetalation, aldehyde addition sequence to install E-trisubstituted olefin and C7 stereocenter, and the first use of an intramolecular Buchwald-like amidation reaction to close the 19-membered macrolactam.     

New renin inhibitors with pseudodipeptidic units in P(1)-P(1') and P(2')-P(3') positions

A series of four new potential renin inhibitors has been synthesized. The structure of the compounds was designed in such a way as to produce agents resistant to enzymatic degradation, metabolically stable, possibly potent and with improved oral absorption. All positions of the 8-13 fragment of the human angiotensinogen were occupied by unnatural units (two unnatural amino acids in positions P(3) and P(2) and two pseudodipeptides in positions P(1)-P(1') and P(2')-P(3')). Both N- and C-terminal functions of the inhibitors were blocked with tert-Boc and ethyl ester groups. Their hydrophobicity evaluated as a log P value, calculated by a computer method, was 6.57 and 6.08 respectively. All peptides were obtained by the carbodiimide method in solution and purified by chromatography on the SiO(2) column. Their resistance to enzymatic degradation was assayed by determination of stability against chymotrypsin activity. The potency was measured in vitro by a spectrofluorimetric method (assay of Leu-Val-Tyr-Ser released from the N-acetyltetradecapeptide substrate by renin in the presence of the inhibitor). All inhibitors were stable to chymotrypsin. Their IC(50) (M/l) values were: 9.6 x 10(-4) (12), 1.6 x 10(-5) (17), 1.0 x 10(-5) (22) and 1.0 x 10(-5) (23) respectively.