Synthesis of p-amino-N,N′-dihydroxybenzamidine using a TBDMS protecting group protocol

A synthetic route to p-amino-N,N′-dihydroxybenzamidine is established using a TBDMS protecting group strategy starting with p-nitrobenzhydroxamic acid chloride, which is transformed to O,O′-bis(tert-butyldimethylsilyl)-N,N′-dihydroxybenzamidine. Reduction with sodium dithionite occurs without degradation of the dihydroxyamidine functional group. Deprotection with ammonium fluoride is fast and efficient. This is important because no other possibility to synthesize this derivative has been found up to now. Furthermore, TBDMS protecting group strategy is proved to be adaptable to other substituted N,N′-dihydroxybenzamidines.     

Pharmacophore modeling as an efficient tool in the discovery of novel noncompetitive AMPA receptor antagonists

A three-dimensional pharmacophore model for the binding of noncompetitive AMPA receptor antagonists was developed in order to map common structural features of highly active compounds. This hypothesis, which consists of two hydrophobic regions, one hydrogen bond acceptor and one aromatic region, was successfully used as framework for the design of a new class of allosteric modulators containing a tetrahydroisoquinoline skeleton and for in silico screening. The promising biological results suggested that the identified molecules might be useful "lead compounds" for future drug development.     

Micellar chromatographic determination of partition coefficients and associated thermodynamic data for pharmaceutical compounds

Micelle/water partition coefficients were obtained for procaine hydrochloride using micellar liquid chromatography (MLC) to illustrate the potential application of this technique to compounds of pharmaceutical interest. Experiments were conducted over a temperature range which led to calculation of a Gibbs free energy, enthalpy and entropy of transfer for procaine hydrochloride. Successful application of this technique was confirmed using a second compound over a range of temperatures, namely caffeine. Overall, this work confirms that MLC can be used to determine precise and accurate partition coefficients that possibly more closely mimic biological membranes than traditional in vitro systems, namely octanol/water.     

Multimethod analysis of Iranian Ilkhanate ceramics from the Takht-e Soleyman palace

The present work describes an analytical study performed on several pieces of Iranian Ilkhanate glazed ceramics from the Takht-e Soleyman palace (Iran, thirteenth century). Several advanced instrumental techniques, including pyrolysis–gas chromatography–mass spectrometry, Fourier transform IR spectroscopy, light microscopy, X-ray diffraction, scanning electron microscopy–X-ray microanalysis and voltammetry of microparticles, were used. The results obtained led to identification of the chemical and mineralogical composition of the pastes and glazes and the colouring agents. Corrosion processes associated with the extreme burial conditions in which the pieces remained for centuries were characterized in some areas of the glazes. A drying oil was identified as the main component of the organic material that was used as the adhesive for the decorative gold sheets applied on the glazes. This finding is in good agreement with traditional recipes. Interestingly, this drying oil exhibits an unusual composition as the gold sheet preserved it from external ageing agents (light, atmosphere, etc.).     

Sensitive determination of fluoroquinolone residues in waters by capillary electrophoresis with laser-induced fluorescence detection

A sensitive capillary electrophoresis –laser-induced fluorescence method has been developed for the determination of six fluoroquinolones of human (ofloxacin, lomefloxacin, and norfloxacin) and veterinary use (danofloxacin, enrofloxacin, and sarafloxacin) in different kinds of water. Fluorescence detection was achieved using a He-Cd laser, with a wavelength of 325 nm. Separation was performed in a fused-silica capillary, and conditions were optimized to obtain the most adequate separation and with the best sensitivity. The separation was carried out in a 70-cm-long capillary (75 μm internal diameter, effective length 55 cm) by using a 125 mM phosphoric acid separation buffer at pH 2.8, with 36% of methanol. The water sample pretreatment involved the separation and preconcentration of the analytes by solid phase extraction. Two reverse-phase cartridges have been evaluated, namely Oasis hydrophilic–liphophilic balance and Strata-X; the latter provided the best recoveries for the selected analytes. The method shows very low detection limits (0.3–1.9 ng/L) with acceptable recoveries and precisions and has been successfully applied to the analysis of well and tap water samples.     

A thin chip microsprayer system coupled to Fourier transform ion cyclotron resonance mass spectrometry for glycopeptide screening

A thin polymer microchip was coupled with a Fourier transform ion cyclotron resonance (FTICR) 9.4 T mass spectrometer and the method was optimized in negative ion mode for glycopeptide screening. The interface between the polymer microchip and FTICR mass spectrometer consists of an in-laboratory conceived and designed mounting system that exhibits robust and controllable alignment of the chip toward the inlet of the mass spectrometer. The particular attribute of the polymer chip coupled to the FTICR mass spectrometer, to achieve an increase in ionization efficiency and sensitivity under the premise of high mass accuracy of detection, is highlighted by the large number of major and minor glycopeptide structures detected and identified in highly heterogeneous mixtures obtained from urine matrices. Glycoforms expressing various saccharide chain lengths ranging from tri- to dodecasaccharide, bearing up to three sialic acid moieties, could be detected and assigned based on the accuracy of the mass measurement (average mass deviation below 6 ppm) of their molecular ions. -Thin chipESI-FTICRMS is a potent novel system for glycomic screening of complex mixtures, as demonstrated for identification of singly sialylated O-glycosylated amino acids and peptides from urine matrices, and could be considered for general applicability in the glycoanalytical field.     

A study of the OH- -induced beta-elimination reactions of 2-(4-chloroethyl)pyridine, 2-(2-chloroethyl)pyridine, 1-methyl-2-(4-chloroethyl)pyridinium iodide and 1-methyl-2-(2-chloroethyl)pyridinium iodide in acetonitrile/water

Second-order rate constants have been determined for the title reactions in OH(-)/H(2)O and in OH(-)/ (CH(3)CN/H(2)O) [30/70, 60/40, and 85/15 (v/v) mixtures]. A relatively small increase in reactivity is observed for the four substrates upon increasing the percentage of CH(3)CN in the solvent mixture. The methyl activating factors (/) are also slightly affected by the solvent composition. On the other hand, the high acceleration of the reaction by methylation of the pyridine ring amounts to 10(4)-10(6) according to an E1cb mechanism.     

Improved resolution power of electrophoretic fractionation of DNA using a voltage gradient "up and down" application

The improved resolution power of electrophoretic fractionation of DNA in a wide range of molecular masses is demonstrated using an "up and down" application of voltage gradient gel electrophoresis (VGGE). This application also allows separation of different DNA fragments which are poorly fractionated in conventional electrophoresis.     

Syntheses and chemistry of hypervalent cyclo-R4Sb4, cyclo-(RSbE)n[R = 2-(Me2NCH2)C6H4, E = O, S] and precursors

The cyclostibane R(4)Sb(4)(1)(R = 2-(Me(2)NCH(2))C(6)H(4)) was synthesized by reduction of RSbCl(2) with Mg in THF or with Na in liquid NH(3). The reaction of 1 with [W(CO)(5)(THF)] gives the stibinidene complex RSb[W(CO)(5)](2)(2). RSbCl(2) and (RSbCl)(2)E [E = O (6), E = S (8)] react with KOH or Na(2)S in toluene/water to give the heterocycles (RSbE)(n)[E = O, n= 3 (3); E = S, n= 2 (4)]. The chalcogeno-bridged compounds of the type (RSbCl)(2)E [E = O (6), E = S (8)] were synthesized by reaction of RSbCl(2) with KOH or Na(2)S in toluene/water, but also by reaction of RSbCl(2) with the heterocycles (RSbE)(n). The compounds (RSbI)(2)O (7) and (RSbBr)(2)S (9) were prepared via halogen-exchange reactions between (RSbCl)(2)E and NaI (E = O) or KBr (E = S) or by reactions between RSbI(2) and KOH or RSbBr(2) and Na(2)S. The reaction of cyclo-(RSbS)(2) with W(CO)(5)(THF) in THF results in trapping of the cis isomer in cyclo-(RSbS)(2)[W(CO)(5)](5). The solution behaviour of the compounds was investigated by (1)H and (13)C NMR spectroscopy. The molecular structures of compounds 1-7 and 9 were determined by single-crystal X-ray diffraction.