Evaluation of the physico-chemical properties of chitosan as a potential carrier for rifampicin, using voltammetric and spectrophotometric techniques

Rifampicin is an antibiotic which, on a carbon paste electrode, shows an oxidation response of 0.492 V (vs. Ag/AgCl) at pH 7.0, due to the electroactivity of the hydroquinone group. Interaction of rifampicin with chitosan is strongly dependent on pH, species concentrations and contact time between the latter. Compared to the carbon paste electrode, electrodes modified with chitosan showed greater sensitivity, with optimum voltammetric profile obtained at pH 8.0. Spectrophotometric measurements indicate that rifampicin is strongly absorbed by chitosan at pH less than the pKa of the pharmaceutical, such behaviour being favourable for the use of chitosan as a carrier for the controlled release of rifampicin in the intestinal tract.     

Monte-Carlo simulation of stochastic differential systems — a geometrical approach

We develop some numerical schemes for d$d$-dimensional stochastic differential equations derived from Milstein approximations of diffusions which are obtained by lifting the solutions of the stochastic differential equations to higher dimensional spaces using geometrical tools, in the line of the work [A.B. Cruzeiro, P. Malliavin, A. Thalmaier, Geometrization of Monte-Carlo numerical analysis of an elliptic operator: Strong approximation, C. R. Acad. Sci. Paris, Ser. I 338 (2004) 481–486].     

Relationship between Volatile Composition and Bioactive Potential of Vegetables and Fruits of Regular Consumption—An Integrative Approach

In recent years, there has been a growing interest in studying and exploring the potential health benefits of foods, mainly from vegetables and fruits from regular intake. The presence of secondary metabolites, namely polyphenols, carotenoids and terpenes, in certain food matrices seems to contribute to their functional properties, expressed through an increased prevention in the development of certain chronic diseases, namely coronary heart diseases, neurodegenerative diseases, cancer and diabetes. However, some foods’ volatile secondary metabolites also present important bioactive properties, although this is a poorly scientifically explored field. In this context, and in order to explore the potential bioactivity of volatile metabolites in different vegetables and fruits from regular consumption, the volatile composition was established using a green extraction technique, solid phase microextraction in headspace mode (HS-SPME), combined with gas chromatography tandem mass spectrometry (GC-MS). A total of 320 volatile metabolites, comprising 51 terpenic compounds, 45 organosulfur compounds, 31 aldehydes, 37 esters, 29 ketones, 28 alcohols, 23 furanic compounds, 22 hydrocarbons, 19 benzene compounds, 13 nitrogenous compounds, 9 carboxylic acids, 7 ethers, 4 halogenated compounds and 3 naphthalene derivatives, were positively identified. Each investigated fruit and vegetable showed a specific volatile metabolomic profile. The obtained results revealed that terpenic compounds, to which are associated antimicrobial, antioxidant, and anticancer activities, are the most predominant chemical family in beetroot (61%), orange carrot (58%) and white carrot (61%), while organosulfur compounds (antiviral activity) are dominant in onion, garlic and watercress. Broccoli and spinach are essentially constituted by alcohols and aldehydes (enzyme-inhibition and antimicrobial properties), while fruits from the Solanaceae family are characterized by esters in tamarillo and aldehydes in tomato.     

Synthesis of all low-energy stereoisomers of the tris(pyrrolidinoindoline) alkaloid hodgkinsine and preliminary assessment of their antinociceptive activity

The previously unknown stereoisomers 3, 4, ent-1, and ent-4 of the tris(pyrrolidinoindoline) alkaloids hodgkinsine (1) and hodgkinsine B (2) were prepared by stereocontrolled total synthesis. In each synthesis, a catalyst-controlled intramolecular Heck reaction was the key step in appending a third cis-pyrrolidinoindoline ring to a hexacyclic chimonanthine precursor. Results of the preliminary evaluation of these hodgkinsine stereoisomers in the tail flick and capsaicin pain models are reported.     

Formation of pyridin-4(1H)-one versus 1H-azepin-4(7H)-one by treatment of 4-tert-butyldimethylsilyloxy-2-amino-1-aza-bicyclo[4.1.0]hept-3-enes with tetrabutylammonium fluoride

Cycloadducts 3 and 4 were treated with tetrabutylammonium fluoride and rapidly suffer cleavage on the three-membered ring to form either pyridin-4(1H)-one or 1H-azepin-4(7H)-one. When R¹ is an oxycarbonyl or a 2-pyridyl group and R² is a negative charge-stabilizing group (cases 3a,b and 4f) the C-C bond cleaves forming products 5. However, when R²=H (case 3c) the ring expands to seven members. When R¹ is an acyl group the pyridin-4(1H)-one formation includes an unexpected shift of the carbonyl group.     

Vesicle-micelle transition in aqueous mixtures of the cationic dioctadecyldimethylammonium and octadecyltrimethylammonium bromide surfactants

The vesicle-micelle transition in aqueous mixtures of dioctadecyldimethylammonium and octadecyltrimethylammonium bromide (DODAB and C(18)TAB) cationic surfactants, having respectively double and single chain, was investigated by differential scanning calorimetry (DSC), steady-state fluorescence, dynamic light scattering (DLS) and surface tension. The experiments performed at constant total surfactant concentration, up to 1.0 mM, reveal that these homologous surfactants mix together to form mixed vesicles and/or micelles, depending on the relative amount of the surfactants. The melting temperature T(m) of the mixed DODAB-C(18)TAB vesicles is larger than that for the neat DODAB in water owing to the incorporation of C(18)TAB in the vesicle bilayer. The surface tension decreases sigmoidally with C(18)TAB concentration and the inflection point lies around x(DODAB) approximately 0.4, indicating the onset of micelle formation owing to saturation of DODAB vesicles by C(18)TAB molecules. When x(DODAB)>0.5 C(18)TAB molecules are mainly solubilised by the vesicles, but when x(DODAB)<0.25 micelles are dominant. Fluorescence data of the Nile Red probe incorporated in the system at different surfactant molar fractions indicate the formation of micelle and vesicle structures. These structures have apparent hydrodynamic radius R(H) of about 180 and 500-800 nm, respectively, as obtained by DLS measurements.     

Synthesis and characterization of nickel nanoparticles dispersed in imidazolium ionic liquids

The diameter and size-distribution of Ni nanoparticles prepared by the decomposition of [bis(1,5-cyclooctadiene)nickel(0)] organometallic precursor dissolved in 1-alkyl-3-methylimidazolium N-bis(trifluoromethanesulfonyl) amide ionic liquids depend on the length of the alkyl side-chain of the imidazolium ring. The increase of the organization range order of the ionic liquid that increases with that of the alkyl side-chain (from n-butyl to n-hexadecyl) induces the formation of nanoparticles with a smaller diameter and size-distribution. The cubic fcc Ni nanoparticles with 4.9 +/- 0.9 to 5.9 +/- 1.4 nm in mean diameter and monomodal size-distribution thus prepared are probably composed of a small cap layer of NiO around a core of Ni metal. The contribution of the oxide layer also depends on the medium i.e. the metal oxide ratio increases in salts containing four to eight carbons on their side-chains and then decreases as the number of carbons increases. The Ni nanoparticles dispersed in the ionic liquids are active catalysts for the hydrogenation of olefins under relatively mild reaction conditions.     

A new dinuclear heme-copper complex derived from functionalized protoporphyrin IX

A new biomimetic model for the heterodinuclear heme/copper center of respiratory oxidases is described. It is derived from iron(III) protoporphyrin IX by covalent attachment of a Gly-L-His-OMe residue to one propionic acid substituent and an amino-bis(benzimidazole) residue to the other propionic acid substituent of the porphyrin ring, yielding the Fe(III) complex 1, and subsequent addition of a copper(II) or copper(I) ion, according to needs. The fully oxidized Fe(III)/Cu(II) complex, 2, binds azide more strongly than 1, and likely contains azide bound as a bridging ligand between Fe(III) and Cu(II). The two metal centers also cooperate in the reaction with hydrogen peroxide, as the peroxide adducts obtained at low temperature for 1 and 2 display different optical features. Support to this interpretation comes from the investigation of the peroxidase activity of the complexes, where the activation of hydrogen peroxide has been studied through the phenol coupling reaction of p-cresol. Here the presence of Cu(II) improves the catalytic performance of complex 2 with respect to 1 at acidic pH, where the positive charge of the Cu(II) ion is useful to promote O-O bond cleavage of the iron-bound hydroperoxide, but it depresses the activity at basic pH because it can stabilize an intramolecular hydroxo bridge between Fe(III) and Cu(II). The reactivity to dioxygen of the reduced complexes has been studied at low temperature starting from the carbonyl adducts of the Fe(II) complex, 3, and Fe(II)/Cu(I) complex, 4. Also in this case the adducts derived from the Fe(II) and Fe(II)/Cu(I) complexes, that we formulate as Fe(III)-superoxo and Fe(III)/Cu(II)-peroxo exhibit slightly different spectral properties, showing that the copper center participates in a weak interaction with the dioxygen moiety.     

Statistical mixture design optimization of extraction media and mobile phase compositions for the characterization of green tea

The influence of different solvents on the extraction medium and the RP-HPLC mobile phase composition were investigated by statistical mixture designs to optimize solvent proportions to prepare the fingerprint of a medicinal herbal extract. For modeling, the number of peaks was used as a measure of fingerprint information. The optimum compositions of solvent to extract chemical substances from green tea and for mobile phase chromatographic analysis were ethyl acetate/ ethanol/dichloromethane (20:5:75 v/v/v) and MeOH/ACN/water (7.5:57.5:35 v/v/v), respectively. This system results in 26 peaks in the chromatographic fingerprint. These results show that an incorrect choice of modifiers for mobile phase composition and solvent extraction hampers the detection of a maximum number of peaks and produces a poor chromatographic fingerprint.     

Analysis of tricyclic antidepressant drugs in plasma by means of solid-phase microextraction-liquid chromatography-mass spectrometry

Solid-phase microextraction coupled to liquid chromatography and mass spectrometry (SPME-LC-MS) was used to analyze tricyclic antidepressant drugs desipramine, imipramine, nortriptyline, amitriptyline, and clomipramine (internal standard) in plasma samples. SPME was performed by direct extraction on a PDMS/DVB (60 microm) coated fiber, employing a stirring rate of 1200 rpm for 30 min, pH 11.0, and temperature of 30 degrees C. Drug desorption was carried out by exposing the fiber to the liquid chromatography mobile phase for 20 min, using a labmade SPME-LC interface at 50 degrees C. The main variables experimentally influencing LC-MS response were evaluated and mathematically modeled. A rational optimization with fewer experiments was achieved using a factorial design approach. The constructed empirical models were adjusted with 96-98% of explained deviation allowing an adequate data set comprehension. The chromatographic separation was realized using an RP-18 column (150 mm x 2.1 mm, 5 microm particles) and ammonium acetate buffer (0.01 mol/l, pH 5.50) : acetonitrile (50 : 50 v/v) as mobile phase. Low detection levels were achieved with electrospray interface (0.1 ng/ml). The developed method showed specificity, linearity, precision, and limit of quantification adequate to assay tricyclic antidepressant drugs in plasma.