Publications

Abstract Numerical parameters of the molecular networks, also referred as Topological Indices or Connectivity Indices (CIs), have been used in Bioorganic and Medicinal Chemistry to find Quantitative Structure-Activity, Property or Toxicity Relationship (QSAR, QSPR and QSTR) models. QSPR models generally use CIs as inputs to predict the biological activity of compounds. However, the literature does not evidence a great effort to find QSAR-like models for other biologically and chemically relevant systems. For instance, blood proteome constitutes a protein-rich information reservoir, since the serum proteome Mass Spectra (MS) represents a potential information source for the early detection of Biomarkers for diseases and/or drug-induced toxicities. The concept of mass spectrum network (MS network) for a single protein is already well-known. However, there are no reported results on the use of CIs for a MS network of a whole proteome to explore MS patterns. In this work, we introduced for the first time a novel network representation and the CIs for the MS of blood proteome samples. The new network bases on Randic's Spiral network have been previously introduced for protein sequences. The new MS CIs, called here Spiral Markov Connectivity (SMCk) of the MS Spiral graph can be calculated with the software MARCH-INSIDE, combining network and Markov model theory. The SMCk values could be used to seek QSAR-like models, called in this work Quantitative Proteome-Property Relationships (QPPRs). We calculate the SMCk values for 62 blood samples and fit a QPPR model by discriminating proteome MS, typical of individuals susceptible to suffer drug-induced cardiotoxicity from control samples. The accuracy, sensitivity, and specificity values of the QPPR model were between 73.08% and 87.5% in training and validation series. This work points to QPPR models as a powerful tool for MS detection of biomarkers in proteomics.

Abstract The standard (p(o)=0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T=298.15 K, for 2,5-dimethylpyrazine (2,5-DMePz) and for the two dimethylpyrazine-N,N'-dioxide derivatives, 2,3-dimethylpyrazine-1,4-dioxide (2,3-DMePzDO) and 2,5-dimethyl-pyrazine-1,4-dioxide (2,5-DMcPzDO), were derived from the measurements of standard massic energies of combustion, using a static bomb calorimeter, and from the standard molar enthalpies of vaporization or sublimation, measured by Calvet microcalorimetry. The mean values for the molar dissociation enthalpy of the nitrogen-oxygen bonds, < DHmo >(N-O), were derived for both N,N'-dioxide compounds. These values are discussed in terms of the molecular structure of the two N,N'-dioxide derivatives and compared with < DHmo >(N-O) values previously obtained for other N-oxide derivatives.

Abstract Ionic liquids (ILs) have recently garnered increased attention because of their potential environmental benefits as "green" replacements over conventional volatile organic solvents. While ILs cannot significantly volatilize and contribute to air pollution, even the most hydrophobic ones present some miscibility with water posing environmental risks to the aquatic ecosystems. Thus, the knowledge of ILs toxicity and their water solubility must be assessed before an accurate judgment of their environmental benefits and prior to their industrial applications. In this work, the mutual solubilities for [C(2)-C(8)mim][Tf(2)N] (n-alkyl-3-methylimidazolium bis-(trifluoromethylsulfonyl)imide) and water between 288.15 and 318.15 K at atmospheric pressure were measured. Although these are among the most hydrophobic ionic liquids known, the solubility of water in these compounds is surprisingly large, ranging from 0.17 to 0.36 in mole fraction, while the solubility of these ILs in water is much lower ranging from 3.2 x 10(-5) to 1.1 X 10(-3) in mole fraction, in the temperature and pressure conditions studied. From the experimental data, the molar thermodynamic functions of solution and solvation such as Gibbs energy, enthalpy, and entropy at infinite dilution were estimated, showing that the solubility of these ILs in water is entropically driven. The predictive capability of COSMO-RS, a model based on unimolecular quantum chemistry calculations, was evaluated for the description of the binary systems investigated providing an acceptable agreement between the model predictions and the experimental data both with the temperature dependence and with the ILs structural variations.

Abstract Thermophysical and thermochemical studies have been carried out for crystalline parabanic acid. The thermophysical study was made by differential scanning calorimetry, DSC, over the temperature interval between T = (263 and 473) K. Two phase transitions were found: at T = (392.3 +/- 1.6) K with the enthalpy of transition of (2.1 +/- 0.4) kJ . mol(-1) and at T = (509.8 +/- 1.5) K, when the compound was scanned to its fusion temperature. The standard (p degrees = 0.1 MPa) molar enthalpy of formation, at T = 298.15 K, for crystalline parabanic acid was determined using static-bomb combustion calorimetry as -(590.2 +/- 1.0) kJ . mol(-1). The standard molar enthalpy of sublimation, at T = 298.15 K, was 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 enthalpy of formation in the gaseous phase, at T = 298.15 K, as -(470.8 +/- 1.2) kJ . mol(-1).

Abstract A series of newly hydrophobically modified polymers (dexC(16)) with different degrees of substitution (DSC16) have been synthesized. They can self-assemble to form micelle-like aggregates through association of the hydrophobic alkyl chains in aqueous solution. The self-aggregation processes, i.e. the critical micelle concentrations (cmc's) of the polymers were characterized by steady-state fluorescence. Further, the interaction between these dexC(16) polymers and ionic surfactants (SOS, SDS and DTAC) was investigated by isothermal titration calorimetry (ITC). For the studied mixed systems some important parameters can be derived from calorimetric titration curves, such as interaction enthalpies, critical concentrations and enthalpies of aggregation. The critical concentrations and the aggregation behaviour for the dexC(16)/SDS system were confirmed by fluorescence measurements. The effects of hydrophobic side group concentrations on the interaction were evaluated in detail. Importantly, we show that the aggregation behaviour of the mixed systems depends on the molar ratio of surfactant to hydrophobic side group (R=n(s)/n(side) (group)).

Abstract The standard (p degrees = 0.1 MPa) molar enthalpies of formation of crystalline bis(dibenzoylmethanate)zinc(II), Zn(DBM)(2), diaquobis(thenoyltrifluoroacetonate)zinc(II), Zn(TTFA)(2)(H(2)O)(2), bis(monothiodibenzoylmethanate)zinc(II), Zn(HDBMS)(2), and bis(monothio-thenoyltrifluoroacetonate)zinc(II), Zn(HTTFAS)(2), were determined, at T = 298.15 K, by high precision solution-reaction calorimetry. The standard molar enthalpy of dehydration of the diaquobis(thenoyltrifluoroacetonate)zinc(II), Zn(TTFA)(2)(H(2)O)(2), complex was measured by high-temperature Calvet microcalorimetry. From the standard molar enthalpies of formation of the complexes in the gaseous state, the mean molar dissociation enthalpies zinc(II)-ligand, (D(m))Zn-L), were derived. [GRAPHICS]

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.