Publications

Abstract The oxidative behavior of viloxazine was studied at a glassy carbon electrode in different buffer systems using cyclic, differential pulse and square-wave voltammetry. The oxidation process was shown to be diffusion-controlled and irreversible over the studied pH. The voltammetric study of the model compounds, 2-ethoxyanisole and morpholine, associated with quantum mechanical (DFT) calculations, allowed to elucidate the oxidation mechanism of viloxazine. An analytical method was developed for the quantification of viloxazine using an acetate pH 5 buffer solution as a supporting electrolyte. A linear response was obtained in the range 7 to 45 mu M, with a detection limit of 0.8 mu M. Validation parameters such as sensitivity, precision and accuracy were evaluated. The proposed method was successfully applied to the determination of viloxazine in pharmaceutical formulations and in human serum. The results were statistically compared with those obtained through an established high-performance liquid chromatography technique, no significant differences having been found between the two methods.

Abstract The energetics and partition of two hybrid peptides of cecropin A and melittin (CA(1-8)M(1-18) and CA(1-7)M(2-9)) with liposomes of different composition were studied by time-resolved fluorescence spectroscopy, isothermal titration calorimetry, and surface plasmon resonance. The study was carried out with large unilamellar vesicles of three different lipid compositions: 1,2-dimyristoil-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG), and a 3:1 binary mixture of DMPC/DMPG in a wide range of peptide/lipid ratios. The results are compatible with a model involving a strong electrostatic surface interaction between the peptides and the negatively charged liposomes, giving rise to aggregation and precipitation. A correlation is observed in the calorimetric experiments between the observed events and charge neutralization for negatively charged and mixed membranes. In the case of zwitterionic membranes, a very interesting case study was obtained with the smaller peptide, CA(1-7)M(2-9). The calorimetric results obtained for this peptide in a large range of peptide/lipid ratios can be interpreted on the basis of an initial and progressive surface coverage until a threshold concentration, where the orientation changes from parallel to perpendicular to the membrane, followed by pore formation and eventually membrane disruption. The importance of negatively charged lipids on the discrimination between bacterial and eukaryotic membranes is emphasized.

Abstract This work is focussed on the thermodynamics of phase transition for some naphthalene derivatives: 1-phenyinaphthalene, 2-phenylnaphthalene, 2-(biphen-3-yl)naphthalene, and 2-(biphen-4-yl)naphthalene. The Knudsen mass-loss effusion technique was used to measure the vapour pressures of the following compounds: 2-phenylnaphthalene (cr), between T = (333.11 and 353.19) K: 2-(biphen-4-yl)naphthatene (cr), between T = (405.17 and 437.19) K; 2-(biphen-3-yl)naphthalene (1), between T = (381.08 and 413.17) K. From the temperature dependence of the vapour pressure, the standard, (p degrees = 10(5) Pa), molar enthalpies, entropies, and Gibbs free energies of sublimation for 2-phenylnaphthalene and 2-(biphen-4-yl)naphthalene were derived as well as the standard molar enthalpy, entropy, and Gibbs free energy of vaporization for 2-(biphen-3-yl)naphthalene at 298.15 K. The temperatures and the standard molar enthalpies of fusion were measured by differential scanning calorimetry and the standard molar entropies of fusion were derived. For 1-phenyl naphthalene the standard molar enthalpy of vaporization at 298.15 K was measured directly using the Calvet microcalorimetry drop method. The 1-phenyinaphthalene is liquid at room temperature, showing a remarkably low melting point when compared to the 2-phenylnaphthalene isomer and naphthalene. A regular decrease of volatility with the increase of a phenyl group in para position at the 2-naphthalene derivatives was observed. In 2-(biphen3-yl)naphthalene, the meta substitution of the phenyl group results in a significantly higher volatility than in the respective para isomer.

Abstract Methamphetamine (METH) is a powerful psychostimulant whose noxious effects depend largely on the pattern of abuse. METH-induced glutamate release may overactivate N-methyl-d-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (NMDAR and AMPAR, respectively) causing excitotoxicity. In the brain, these receptors are also known for their essential role in mediating memory consolidation. Therefore, we assessed glial fibrillary acidic protein (GFAP) expression as a marker for astrogliosis and neurodegeneration by using Fluoro Jade C (F-J C) staining. Moreover, we investigated the effect of two METH regimens on NMDAR NR1 and NR2A and on AMPAR GluR2 subunit expression in the rat striatum and frontal cortex 24 h after drug treatment. Adult Sprague-Dawley rats were injected subcutaneously (s.c.) on six consecutive days with saline (control and acute groups) or with an increasing dose of METH (10, 15, 15, 20, 20, 25 mg/kg/day; ED group). On the seventh day, both METH groups were given a "bolus" of 30 mg/kg METH, whereas controls received saline. We evaluated the expression levels of GFAP by both Western blot and immunohistochemical assays and concluded that there was no difference from control levels. In addition, neither drug regimen resulted in neurodegeneration within 24 h of last METH administration. In the frontal cortex of the acute group, NR1 expression level was decreased, and both NR2A and GluR2 were increased. Also, in the striatum of the acute group, the expression level of GluR2 was significantly increased, and both GluR2 and NR2A levels were augmented in the striatum of the ED group. Taken together, these results suggest a protective mechanism by decreasing permeability and/or functionality of AMPAR and NMDAR to counteract METH-induced glutamate overflow in the brain. Moreover, these results may explain, in part, the mnemonic deficits and psychotic behavior associated with METH abuse.

Abstract Lycotoxin I and Lycotoxin II are natural anti-microbial peptides, that were identified in the venom of the Wolf Spider Lycosa carolinensis. These peptides were found to be potent growth inhibitors for bacteria (Escherichia coli) and yeast (Candida glabrata) at micromolar concentrations. Recently, shortened analogues of Lycol and LycoII have been reported to have decreased haemolytic effects. A shorter Lyco-I analogue studied, Lycol 1-15 (H-IWLTALKFLGKHAAK-NH2), was active only above 10 pm, but was also the least haemolytic. On the basis of these findings, we became interested in obtaining a deeper insight into the membrane activity of LycoI 1-15, as this peptide may represent the first major step for the future development of selective, i.e. non-haemolytic, Lycotoxin-based antibiotics. The interaction of this peptide with liposomes of different composition was studied by microcalorimetry [differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC)l and CD. The results obtained from the calorimetric and spectroscopic techniques were jointly discussed in an attempt to further understand the interaction of this peptide with model membranes. Copyright (c) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Abstract A thermophysical and thermochemical study has been carried out for crystalline imidazolidin-2-one and N,N'-trimethyleneurea [tetrahydropyrimidin-2(1H)-one]. The thermophysical study was made by differential scanning calorimetry, d.s.c., in the temperature intervals between T = 268 K and their respective melting temperatures. Several solid-solid transitions have been detected in imidazolidin-2-one. The standard (p degrees = 0.1 M Pa) molar enthalpies of formation, at T = 298.15 K, for crystalline imidazolidin-2-one and N,N'-trimethyleneurea [tetrahydropyrimidin-2(l H)-one], were deter-mined using static-bomb combustion calorimetry. The standard molar enthalpies of sublimation, at T = 298.15 K, for the two compounds were derived from the variation of their vapour pressures, measured by the Knudsen effusion method, with the temperature. These two thermochemical parameters yielded the standard molar enthalpies of formation of the two cyclic urea compounds studied in the gaseous phase at T = 298.15 K. These values are discussed in terms of molecular structural contributions and interpreted on the bases of the "benzo-condensed effect" and of the ring strain of imidazolidin-2-one.

Abstract A novel procedure for solid-phase microextraction fiber preparation is presented, which combines the use of a rigid titanium alloy wire as a substrate with a blend of PDMS sol-gel mixture/silica particles, as a way of increasing both the mechanical robustness and the extracting capability of the sol-gel fibers. The similar to 30 mu m average thick fibers displayed an improvement in the extraction capacity as compared to the previous sol-gel PDMS fibers, due to a greater load of stable covalently bonded sol-gel PDMS. The observed extraction capacity was comparable to that of 100 mu m non-bonded PDMS fiber, having in this case the advantages of the superior robustness and stability conferred, respectively, by the unbreakable substrate and the sol-gel intrinsic characteristics. Repeatability (n = 3) ranged 1-8% while fiber production reproducibility (n = 3) ranged 15-25%. The presence of the silica particles was found to have no direct influence on the kinetics and mechanism of the extraction process, thus being possible to consider the new procedure as a refinement of the previous ones. The applicability potential of the devised fiber was illustrated with the analysis of gasoline under the context of arson samples.

Abstract The interaction between polyelectrolytes based on dextran with pendant N-alkyl-N,N-dimethyl-N-(2-hydroxypropyl) ammonium chloride groups, where n = 2, 4, 8, 12, or 16, and sodium alkyl sulfates, SC(n)S, with n = 8, 10, 12, 14, and 16, has been studied by conductometry and fluorescence techniques. Comparison of cumulative specific conductivities of the mixtures of polymer - surfactant over a large surfactant concentration range, with those of pure surfactant and NaCl, has clearly shown that the surfactants start to bind to polymer at very low concentrations (10(-6) M), forming mixed aggregates. The steady-state emission fluorescence measured in the presence of pyrene, 1,3,6-diphenylhexatriene (DPH), and 1-pyrenylbutyric acid sodium salt demonstrated the existence of a critical surfactant concentration (CAC(S)) at which the previously formed mixed aggregates are interconnected due to self-association of surfactant molecules included in different mixed polymer/surfactant aggregates. Above CAC(S), the mixed aggregates change dramatically their properties (hydrophobicity, size, DPH solubilization) which depend on both polymer and surfactant hydrophobicities and concentrations. The characterization of the new formed aggregates at different surfactant concentration ranges is derived mainly from their ability to solubilize hydrophobic compounds. The variety of fluorescence techniques used, combined with conductometric measurements and previous calorimetric information allowed us to provide here a comprehensive study and new interpretation of the solution behavior of these polymer-surfactant systems.