Synthesis and Biological Evaluation of Glycosides and Acyclic Nucleosides Derived 2‐Oxonicotinonitriles

Synthesis and biological evaluations of a series of 2‐oxonicotinonitriles (2‐ONNs) derivatives are described. Incorporation of branching and solubilizing groups to the 2‐ONN derivative 7 was attained by coupling with several organo‐halides/alkylating agents including three glycosyl bromides under basic conditions. Coupling of 2‐ONNs occurred mainly at the ring nitrogen position and to a lesser extent at the 2‐oxo position giving the O‐alkylated products. Alkylated ONNs and free nucleosides/glycosides derived from the 2‐ONN derivative 7 were tested for their antibacterial, antifungal, and antiviral activities. N‐propargyl and N‐allyl derivatives 23 and 25 showed significant anti‐SARS‐CoV. The N‐butylacetate and O‐allyl derivatives 18 and 26 showed potent antibacterial activities against both Gram‐positive (Staphylococcus aureus, Micrococci luteus) and Gram‐negative (Pseudomonas aeruginosa, Escherichia coli) bacterial strains. The N‐glucoside derivative 8 showed significant antifungal activity.     

Characterization of Maghsail meteorite from Oman by Mössbauer spectroscopy, X-ray diffraction and petrographic microscopy

The meteorite found at Maghsail (16 55 70 N–53 46 69 E) west of Salalah Oman, has been studied by ⁵⁷Fe Mössbauer spectroscopy, X-diffractometry and petrographic microscopy. In the polished section the meteorite exhibits a porphyritic texture consisting of pyroxene and olivine phenocrysts in a fine to medium grained ground mass in addition to minor phases possibly skeletal chromite, troilite and minute amount of iron oxides. X-ray diffraction supports the existence of these compounds. The Mössbauer spectra of powdered material from the core of the rock at 298 K and 78 K exhibit a mixture of magnetic and paramagnetic components. The paramagnetic components are assigned to the silicate minerals olivine and pyroxene. On the other hand, the magnetic spectra reveal the presence of troilite and iron oxides. The petrographic analyses indicate that the iron oxides are terrestrial alteration products.     

Synthesis and reactions of thiosemicarbazides,triazoles, and <Emphasis Type="Italic">Schiff</Emphasis> bases as antihypertensive α-blocking agents

Methyl 2-(thiazol-2-ylcarbamoyl)acetate was synthesized and used as starting material. It was treated with hydrazine hydrate to afford the hydrazide, which was reacted with nitromethane and formaldehyde to give the saturated nitropyrimidine. The hydrazide was reacted with phenyl isothiocyanate to afford the thiosemicarbazide, which was cyclized with ethyl bromoacetate, sodium hydroxide, or sulfuric acid to afford N-phenylthiazolidinone, N-phenyltriazole, and thiadiazolyl derivatives. The methyl 2-(thiazol-2-ylcarbamoyl)acetate was coupled with diazonium salts of aniline, 4-chloroaniline, 4-bromoaniline, or 4-aminobenzenesulfonamide to afford the carbamoyl acetates, which were reacted with 2-aminobenzimidazole, 1,2,4,5-tetrachlorophthalic anhydride, and hydrazine hydrate to afford the corresponding thiazolylmalonamide, tetrachloroisoindolylimide, and tri-azole derivatives. Schiff bases and imides are newly synthesized candidates obtained via simple condensation of the hydrazide with aldehydes, 2,3-pyridinedicarboxylic anhydride, or 1,8-naphthalenedicarboxylic anhydride. The pharmacological screening showed that many of these compounds have good antihypertensive α-blocking activity and low toxicity. Correspondence: Abd El-Galil E. Amr, National Research Center, Applied Organic Chemistry, Dokki, Cairo, Egypt.     

Development of a capillary electrophoresis method for the enantioselective estimation of primaquine in pharmaceutical formulations

A capillary electrophoresis (CE) method has been developed that allows the separation and estimation of primaquine enantiomers using hydroxypropyl-gamma-cyclodextrin (HP-gamma -CD) as a chiral selector. The influence of chemical and instrumental parameters on the separation, such as type and concentration of CD, buffer concentration, buffer pH, applied voltage, capillary temperature, and injection time, were investigated. Good separation of the racemic mixture of primaquine was achieved using a fused-silica capillary (52.5 cm effective length x 50 microm id) and a background electrolyte composed of tris-phosphate buffer solution (50 mM, pH 2.5) containing 15 mM HP-gamma-CD as a chiral selector. The recommended applied voltage, capillary temperature, and injection time were 15 kV, 25 degrees C, and 6 s, respectively. Within-day and interday reproducibility of peak area and migration time gave relative standard deviation values ranging from 1.05-3.30%. Good recoveries (range of 96.8-104.9%) were obtained from the determination of placebos that were spiked with 0.25-1.00 mg/L primaquine. The proposed CE method was successfully applied to the assay of primaquine diphosphate in pharmaceutical formulations (tablets).     

Density functional theory studies of conformational stabilities and rotational barriers of 2- and 3-thiophenecarboxaldehydes

The molecular structures, conformational stabilities, and infrared vibrational wavenumbers of 2-thiophenecarboxaldehyde and 3-thiophenecarboxaldehyde are computed using Becke-3–Lee–Yang–Parr (B3LYP) with the 6-311++G** basis set. From the computations, cis-2-thiophenecarboxaldehyde is found to be more stable than the transfer conformer with an energy difference of 1.22 kcal/mol, while trans-3-thiophenecarboxaldehyde is found to be more stable than the cis conformer by 0.89 kcal/mol. The computed dipole moments, structural parameters, relative stabilities of the conformers and infrared vibrational wavenumbers of the two molecules coherently support the experimental data in the literature. The normal vibrational wavenumbers are characterized in terms of the potential energy distribution using the VEDA4 program. The effect of solvents on the conformational stability of the molecules in nine different solvents is investigated using the polarizable continuum model.     

Determination of quinocide as impurity in primaquine tablets by capillary zone electrophoresis

A capillary zone electrophoretic method has been developed and validated for the determination of the impurity quinocide (QC) in the antimalarial drug primaquine (PQ). Different buffer additives such as native cyclodextrins and crown ethers were evaluated. Promising results were obtained when either β‐cyclodextrin (β‐CD) or 18‐crown‐6 ether (18C6) were used. Their separation conditions such as type of buffer and its pH, buffer additive concentration, applied voltage capillary temperature and injection time were optimized. The use of 18C6 offers slight advantages over β‐CD such as faster elution times and improved resolution. Nevertheless, migration times of less than 5 min and resolution factors (R_s) in the range of 2–4 were obtained when both additives were used. The method was validated with respect to selectivity, linearity, limits of detection and quantitation, analytical precision (intra‐ and inter‐day variability) and repeatability. Concentrations of 2.12 and 2.71% (w/w) of QC were found in pharmaceutical preparations of PQ from two different manufacturers. A possible mechanism for the successful separation of the isomers is also discussed. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of the First Tellurium‐Derivatized Oligonucleotides for Structural and Functional Studies

We report here the first synthesis of Te‐nucleoside phosphoramidites and Te‐modified oligonucleotides. We protected the 2′‐tellurium functionality by alkylation and found that the Te functionality is compatible with solid‐phase synthesis and that the Te oligonucleotides are stable during deprotection and purification. In addition, the redox properties of the Te functionalities have been explored. We found that the telluride and telluoxide DNAs are interchangeable by redox reactions. At elevated temperature, the Te‐DNA can also be site‐specifically fragmented oxidatively or reductively when 2′‐TePh functionality is present, whereas elimination of the nucleobase is observed in the presence of 2′‐TeMe. Moreover, the stability of the DNA duplexes derivatized with the Te functionalities has been investigated. Our Te derivatization of nucleic acids provides a novel approach for investigating DNA damage as well as for structure and function studies of nucleic acids and their protein complexes.     

Determination of aminoglutethimide enantiomers in pharmaceutical formulations by capillary electrophoresis using methylated-β-cyclodextrin as a chiral selector and computational calculation for their respective inclusion complexes

A capillary electrophoretic method for the separation of the aminoglutethimide (AGT) enantiomers using methylated-β-cyclodextrin (M-β-CD) as chiral selector is described. Several parameters affecting the separation were studied, including the type and concentration of chiral selector, buffer pH, voltage and temperature. Good chiral separation of the racemic mixture was achieved in less than 9 min with resolution factor Rs = 2.1, using a fused-silica capillary and a background electrolyte (BGE) of tris-phosphate buffer solution (50 mmol L⁻¹, pH 3.0) containing 30 mg mL⁻¹ of M-β-CD. The separation was carried out in normal polarity mode at 25 °C, 16 kV and using hydrostatic injection. Acceptable validation criteria for selectivity, linearity, precision, and accuracy/recovery were included. The proposed method was successfully applied to the assay of AGT enantiomers in pharmaceutical formulations. The computational calculations for the inclusion complexes of the R- and S-AGT-M-β-CD rationalized the reasons for the different migration times between the AGT enantiomers.     

Lie algebraic approach of a charged particle in presence of a constant magnetic field via the quadratic invariant

In this paper we consider the problem of a charged harmonic oscillator under the influence of a constant magnetic field. The system is assumed to be isotropic and the magnetic field is applied along the z-axis. The canonical transformation is invoked to remove the interaction term and the system is reduced to a model containing the second harmonic generation. Two classes of the real and complex quadratic invariants (constants of motion) are obtained. We have employed the Lie algebraic technique to find the most general solution for the wave function for both real and complex invariants. Some discussions related to the advantage of using the quadratic invariants to solve the Cauchy problem instead of the direct use of the Hamiltonian itself are also given.