Chemoenzymatic Synthesis of Stannylated Metomidate as a Precursor for Electrophilic Radiohalogenations – Regioselective Alkylation of Methyl 1<Emphasis Type="Italic">H</Emphasis>-Imidazole-5-carboxylate [1]

Summary. Metomidate (ee 99%) substituted with iodine in the phenyl ring was prepared from (S)-1-(4-iodophenyl)ethanol (ee >98%) obtained by lipase-catalysed resolution and methyl 1H-imidazole- 5-carboxylate. The two fragments were joined highly regioselectively (alkylation only at N-1 of substituted imidazole) with inversion of configuration using the Mitsunobu reaction. Finally, p-iodometomidate was transformed into the p-trimethylstannyl derivative.     

Stepwise optimization approach for improving LC‐MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design

In this article, a step‐by‐step optimization procedure for improving analyte response with implementation of experimental design is described. Zwitterionic antiepileptics, namely vigabatrin, pregabalin and gabapentin, were chosen as model compounds to undergo chloroformate‐mediated derivatization followed by liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) analysis. Application of a planned stepwise optimization procedure allowed responses of analytes, expressed as areas and signal‐to‐noise ratios, to be improved, enabling achievement of lower limit of detection values. Results from the current study demonstrate that optimization of parameters such as scan time, geometry of ion source, sheath and auxiliary gas pressure, capillary temperature, collision pressure and mobile phase composition can have a positive impact on sensitivity of LC‐MS/MS methods. Optimization of LC and MS parameters led to a total increment of 53.9%, 83.3% and 95.7% in areas of derivatized vigabatrin, pregabalin and gabapentin, respectively, while for signal‐to‐noise values, an improvement of 140.0%, 93.6% and 124.0% was achieved, compared to autotune settings. After defining the final optimal conditions, a time‐segmented method was validated for the determination of mentioned drugs in plasma. The method proved to be accurate and precise with excellent linearity for the tested concentration range (40.0 ng ml^?1–10.0 × 10³ ng ml^?1). Copyright © 2013 John Wiley & Sons, Ltd.     

Computational Studies on Selected Macrolides Active against Escherichia coli Combined with the NMR Study of Tylosin A in Deuterated Chloroform

Although many antibiotics are active against Gram-positive bacteria, fewer also show activity against Gram-negative bacteria. Here, we present a combination of in silico (electron ion-interaction potential, molecular docking, ADMET), NMR, and microbiological investigations of selected macrolides (14-membered, 15-membered, and 16-membered), aiming to discover the pattern of design for macrolides active against Gram-negative bacteria. Although the conformational studies of 14-membered and 15-membered macrolides are abundant in the literature, 16-membered macrolides, and their most prominent representative tylosin A, have received relatively little research attention. We therefore report the complete ¹H and ¹³C NMR assignment of tylosin A in deuterated chloroform, as well as its 3D solution structure determined through molecular modelling (conformational search) and 2D ROESY NMR. Additionally, due to the degradation of tylosin A in deuterated chloroform, other species were also detected in 1D and 2D NMR spectra. We additionally studied the anti-bacterial activity of tylosin A and B against selected Gram-positive and Gram-negative bacteria.     

Kinetic studies on the reactions of [Pd(dach)(X-Y)] complexes with some DNA constituents

The kinetics of complex-formation reactions of six Pd(dach) complexes, dach = 1,2-trans-R,R-diaminocyclohexane, viz. [Pd(dach)Cl2], [Pd(dach)(H2O)2]2+, and four complexes with different chelating leaving groups X-Y, viz. [Pd(dach)(O,O-cyclobutane-1,1-dicarboxylate)], [Pd(dach)(N,O-glycine)](+), [Pd(dach)(N,S-methionine)]+ and [Pd(dach)(O,O-oxalate)], were studied. The effect of the leaving group on the lability of the resulting Pd(ii) complexes was studied for the nucleophiles inosine, inosine-5'-monophosphate and guanosine-5'-monophosphate under pseudo-first-order conditions as a function of nucleophile concentration, temperature and pressure using stopped-flow techniques. Two consecutive reaction steps, which both depend on the nucleophile concentration, were observed. The rate constants for all reactions indicate a direct substitution of the X-Y chelate by the selected nucleophiles, thereby showing that the nature of the chelate, viz. O-O (cbdca), (ox), N-O (gly) or S-N (l-met), plays an important role in the kinetic and mechanistic behavior of the Pd(ii) complexes. The mechanism of the substitution reactions is associative in nature as supported by the large and negative values of DeltaS(double dagger) and DeltaV(double dagger).     

Lead(IV) oxide-graphite composite electrodes: application to sensing of ammonia, nitrite and phenols

Carbon powder modified with lead(IV) oxide was synthesised by a wet impregnation procedure from concentrated lead(II) nitrate solution. The impregnated powder was subsequently thermally treated at 823 K. Electrochemical and spectroscopic characterisation of the modified powder showed that lead(IV) oxide has been formed during the procedure. A novel composite lead(IV) oxide modified carbon powder epoxy electrode was developed for electrocatalytic sensing of gaseous, inorganic and organic analytes. The behaviour and analytical advantages of the composite electrode are evaluated with respect to determination of ammonia, nitrite ions and several different phenols. It has been demonstrated that the composite electrode can be used to analyze these analytes in standard aqueous solutions with competitively low limits of detection.     

Metal ion-molecule kinetics at combustion temperatures: The reaction of Ca with O2

The high-temperature photochemistry (HTP) technique, previously used for reactions of neutral species, has been adapted to the study of atomic metal ion-molecule reactions. Ca⁺ ions were generated by 193 nm multi-photon photolysis of calcium acetyl acetonate and its pyrolysis fragments. The relative ion concentrations were monitored by laser-induced fluorescence at 393.4 nm. Ar was used as the bath gas. The data for the Ca⁺ + O₂ + M → CaO₂⁺ + M association reaction (1) are fitted by k₁(907-1425 K) = 3.5 × 10⁻³² exp(+3161 K/T) cm⁶ molecule⁻² s⁻¹. Combining with an approximate k₁(296 K) value in the literature leads to k₁(296-1425 K) = 5.8 × 10⁻²² (T/K)^−2.9 exp(−601 K/T) cm⁶ molecule⁻² s⁻¹. Over much of the observed temperature range reaction (1) has much smaller rate coefficients than the corresponding neutral Ca association reaction. Reaction (1) is shown to behave very similarly to the O₂ association reaction with neutral K atoms, with which Ca⁺ is iso-electronic. This suggests that the initial step is ion-pair complex formation of the superoxide Ca²⁺(O₂)⁻, which is also consistent with results from density functional calculations. The k₁ values are rationalized via Troe’s unimolecular formalism, which leads to good accord with the experiments.     

Second harmonic wave generation from Joule heating in layered organic conductors

The amplitude of a second harmonic wave (SHW) generated from Joule heating as a heat source in organic conductor β-(BEDT-TTF)₂IBr₂ is analyzed as a function of the magnetic field strength and its orientation with respect to the plane of the layers. Angular oscillations of the SHW amplitude are correlated with the angular changes of in-plane conductivity that arise from the periodic dependence of charge carriers velocity on the field orientation. It was found that the nonlinear effect of wave generation leads to a shift between the position of the peaks of the wave amplitude and in-plane conductivity. This allows an important information on the parameter values of organic conductors as well as wave velocity to be obtained. Magnetic field dependence shows that the wave is not strongly attenuated with increasing field and might give insights on the interactions between the electromagnetic, temperature and acoustic oscillations. We found that these observations are completely different compared to those of linear acoustic wave generation. It has been shown that the necessary conditions for observing the nonlinear acoustic wave generation are fulfilled in a wide range of fields and angles that allow the acoustic properties of organic conductors to be studied in detail.     

A simulation of neutron interaction from Am–Be source with the CR-39 detector

Presented in this paper is a simulation of the interaction of neutrons emitted from a cylindrical Am–Be source with a CR-39 detector. A Fortran90 program, called Neutron.f90, has been written to determine the specifications of secondary particles (alpha particle or proton) and the kinematics of the interactions. A Monte Carlo method was used to simulate which interactions occurred with the constituents of the CR-39 detector, H, C and O atoms. Due to the detector composition, elastic and nonelastic scattering of neutrons is possible. In this paper, nonelastic scattering includes: inelastic scattering; the emission of an alpha particle (n,α) reaction and the emission of a proton (n,p) reaction. Cross sections of other reactions are very small and negligible in comparison with the above mentioned. The energy deposited per unit mass per one neutron was calculated. In addition the contribution to the energy deposited by the alpha particles and protons were determined separately. The program Neutron.f90 computes the coordinates of points in which interactions occur i.e. where secondary particles appear. The energy and angular distributions of protons are also represented in this paper. Another Fortran90 program, called Track_Visibility.f90, was written to calculate the number of visible proton tracks and to calculate the energy deposited per one neutron per one visible track.     

On k-circulant matrices (with geometric sequence)

Let k be a nonzero complex number. In this paper we show how the inverse of a nonsingular k-circulant matrix can be obtained. The method is used to determine the inverse of a nonsingular k-circulant matrix with geometric sequence. If k = 1, then we get the result presented in the paper A.C.F. Bueno, Right Circulant Matrices With Geometric Progression, Int. J. Appl. Math. Res. 1(4) (2012), 593– 603. Also, we derive the Moore-Penrose inverse of a singular k-circulant matrix with geometric sequence. At the end of the paper, we illustrate the obtained results by examples.