Publications

Abstract Glioblastoma (GBM), the highest grade astrocytoma, is one of the most aggressive and challenging cancers to treat. The standard treatment is usually limited due to the intrinsic resistance of GBM to chemotherapy and drug non-specific effects. Therefore, new therapeutic strategies need to be developed to target tumor cells, sparing healthy tissues. In this context, the inhibitor-of-apoptosis protein (IAP) survivin emerges as an ideal target for a gene silencing approach, since it is sharply differentially expressed in cancer tissues. In this work, two different families of cationic gemini surfactants (bis-quat conventional and serine-derived) were tested regarding their efficiency to deliver small interfering RNAs (siRNAs) in a human GBM cell line (U87), in order to select an effective siRNA anti-survivin carrier. Importantly, survivin downregulation combined with administration of the chemotherapeutic agents temozolomide or etoposide resulted in a synergistic cytotoxic effect, thus revealing to be a promising strategy to reduce the chemotherapeutic doses for GBM treatment.

Abstract This paper reports experimental vapor pressures of condensed phases of methyl p-cyano, p-formyl, p-nitro, and p-(methylamino) benzoates measured over the temperature ranges (303.9 to 393.0) K, (303.1 to 388.2) K, (319.0 to 415.8) K, and (332.9 to 392.4) K, respectively, using a static method based on capacitance diaphragm manometers. The Knudsen mass-loss effusion technique was also used to measure the vapor pressures of crystalline methyl p-(methylamino)benzoate in the temperature range (317.1 to 339.2)" K. These results enabled the calculation of the standard molar enthalpies and entropies of sublimation and of vaporization, at reference temperatures as well as the (p,T) values of the triple point of each compound. The temperatures and molar enthalpies of fusion were determined using differential scanning calorimetry and were compared with the values derived indirectly from the vapor pressure measurements. The enthalpies of the intermolecular hydrogen bonds O-H center dot center dot center dot O in the crystalline phase of the parent benzoic acids were determined.

Abstract This work reports the experimental determination of relevant thermodynamic properties and the characterization of luminescence properties of the following polycyclic aromatic hydrocarbons (PAHs): 2,6-diethylnaphthalene, 2,6-diisopropylnaphthalene and 2,6-di-tert-butylnaphthalene. The standard (p(o) = 0.1 MPa) molar enthalpies of combustion, Delta H-c(m)o, of the three compounds were determined using static bomb combustion calorimetry. The vapor pressures of the crystalline phase of 2,6-diisopropylnaphthalene and 2,6-di-tert-butylnaphthalene were measured at different temperatures using the Knudsen effusion method and the vapor pressures of both liquid and crystalline phases of 2,6-diethylnaphthalene were measured by means of a static method. The temperatures and the molar enthalpies of fusion of the three compounds were determined using differential scanning calorimetry. The gas-phase molar heat capacities and absolute entropies of the three 2,6-dialkylnaphthalenes studied were determined computationally. The thermodynamic stability of the compounds in both the crystalline and gaseous phases was evaluated by the determination of the Gibbs energies of formation and compared with the ones reported in the literature for 2,6-dimethylnaphthalene. From fluorescence spectroscopy measurements, the optical properties of the compounds studied and of naphthalene were evaluated in solution and in the solid state.

Abstract This work presents a comprehensive experimental and computational study of the thermodynamic properties of 2,7-di-tert-butylfluorene. The standard (p(o) = 0.1 MPa) molar enthalpy of formation in the crystalline phase was derived from the standard molar energy of combustion, measured by static bomb combustion calorimetry. The enthalpies and temperatures of transition between condensed phases were determined from DSC experiments. The vapour pressures of the crystalline and liquid phases were measured between (349.14 and 404.04) K, using two different experimental methods. From these results the standard molar enthalpies, entropies and Gibbs energies of sublimation and of vaporization were derived. The enthalpy of sublimation was also determined using Calvet microcalorimetry. The thermodynamic stability of 2,7-di-tert-butylfluorene in the crystalline and gaseous phases was evaluated by the determination of the standard Gibbs energies of formation, at the temperature 298.15 K, and compared with the ones reported in the literature for fluorene. A computational study at the G3(MP2)//B3LYP and G3 levels has been carried out. A conformational analysis has been performed and the enthalpy of formation of 2,7-di-tert-butylfluorene has been calculated, using atomization and isodesmic reactions. The calculated enthalpies of formation have been compared to the experimental values. (C) 2016 Elsevier Ltd.

Abstract The current work addresses a thermochemical study regarding the compounds N-methylphenothiazine and N-methylphenoxazine. The excellent agreement between the experimental and computational gas-phase enthalpy of formation values obtained for the N-methylphenothiazine reinforced the validation/ calibration of the computational methodology established, allowing the use of it for the homologous oxygen derivative. The computational studies were also extended to the attainment of gas-phase molar heat capacities at different temperatures, dipole moment, electrostatic potential energy maps mapped onto electron density isosurface, and frontier orbitals of N-methylphenothiazine and N-methylphenoxazine. The experimental techniques used were the Knudsen mass-loss effusion, Calvet microcalorimetry and combustion calorimetry aiming, respectively, the determination of the temperature-vapour pressures dependences, the enthalpy of sublimation and the massic energy of combustion of N-methylphenothiazine. These quantities were used to derive the corresponding enthalpy of formation in the gas phase, at T = 298.15 K, (271.3 +/- 4.1) kJ . mol(-1). The results obtained for the enthalpies of formation are discussed and compared with related compounds, providing an opportunity to evaluate the effects in the enthalpies of formation associated with the substitution of the hydrogen of the amino group by a methyl group.

Abstract In the present work the energetic properties of phthalide and phthalic anhydride are assessed experimental and computationally allowing to calculate the standard molar enthalpy of formation, in the gaseous phase, of each compound. These results enabled to analyze and interpret the enthalpic and structural molecular effects of one and two ketone groups in the main structure of phthalan. The high-temperature Calvet microcalorimetry and the static bomb combustion calorimetry were used to measure, respectively, the enthalpy of sublimation and the massic energy of combustion of the two compounds. These data were combined to derive the standard molar enthalpy of formation, in the gaseous phase, of phthalide and phthalic anhydride. The gas-phase enthalpies of formation of phthalide and phthalic anhydride compounds were estimated using the composite G3(MP2)//B3LYP approach together with adequate gas-phase working reactions. The computational study was also extended to phthalan and the reliability of the value obtained for the correspondent gas-phase enthalpy of formation, when compared with the experimental value reported in the literature, contributes to validate the computational methodology used. The good agreement verified between computational and experimental results for the other two phthalan derivatives studied gave us confidence to estimate the gas-phase enthalpy of formation of the 2,5-dihydrofuran that was not studied experimentally. Complementary, natural bond orbital (NBO) calculations were also performed, allowing an advance on the analysis of the structural and reactivity characteristics of this type of compounds.

Abstract The standard ( p degrees = 0.1 MPa) molar enthalpies of formation, in the crystalline phase, of 6-azauracil, 6-azathymine and 6-aza-2-thiothymine at T = 298.15 K, were derived from the standard molar energies of combustion, in oxygen, measured by combustion calorimetry. The standard molar enthalpies of sublimation, at T = 298.15 K, were measured by high temperature Calvet microcalorimetry. For 6-azauracil, the standard molar enthalpy of sublimation, at T = 298.15 K, was determined from the temperature-vapour pressure dependence, obtained by the Knudsen mass-loss effusion method. From the experimental studies, the standard molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, of the 6-azauracil, 6-azathymine and 6-aza-2-thiothymine were derived. The gas-phase enthalpies of formation were also estimated by G3 and G4 calculations which were further extended to the computation of the standard molar enthalpy of formation of 6-aza-2-thiouracil. We compare the values obtained computationally with the experimental data available and find a good agreement between them.

Abstract The standard (p(0) = 0.1 MPa) molar energies of combustion, Delta U-c(m)0, for the crystalline 5-isopropylbarbituric and 2-thiobarbituric acids were determined, at the temperature of 298.15 K, by static bomb or rotating bomb combustion calorimetry, respectively. For 5-isopropylbarbituric acid, the standard molar enthalpy of sublimation, Delta H-g(cr)m(0), at T=298.15 K, was derived by Calvet microcalorimetry. The standard molar enthalpy of sublimation, at T=298.15 K, was derived by the Clausius-Clapeyron equation, from the temperature-vapor pressure dependence, measured by the Knudsen mass-loss effusion method. These experiments allowed the determination of the standard molar enthalpy of formation, in the gaseous phase, at T=298.15 K for 5-isopropylbarbituric acid. For 2-thiobarbituric acid, the gas-phase enthalpy of formation was calculated combining the result derived for the crystalline phase with literature data for the enthalpy of sublimation, at T=298.15 K. These values were compared with estimates obtained from very accurate computational calculations using the G3 and G4 level theory composite methods.

Abstract The standard (p(o) = 0.1 MPa) molar enthalpies of formation, in the crystalline phase, of methyl 1H-indole-3-carboxylate and ethyl 1H-indole-2-carboxylate, at T = 298.15 K, were derived from measurements of the standard massic energies of combustion using a static bomb combustion calorimeter. The Knudsen effusion technique was used to measure the vapour pressures as a function of the temperature, which allowed determining the standard molar enthalpies of sublimation of these compounds. The standard (p(o) = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, were calculated by combining, for each compound, the standard molar enthalpy of formation, in the crystalline phase, and the standard molar enthalpy of sublimation, yielding -(207.6 +/- 3.6) kJ.mol (1) and -(234.4 +/- 2.4) kJ.mol (1), for methyl 1H-indole-3-carboxylate and ethyl 1H-indole-2-carboxylate, respectively. Quantum chemical studies were also conducted, in order to complement the experimental study. The gas-phase enthalpies of formation were estimated from high level ab initio molecular orbital calculations, at the G3(MP2) level, for the compounds studied experimentally, extending the study to the methyl 1H-indole-2-carboxylate and ethyl 1H-indole-3-carboxylate. The results obtained were compared with the experimental data and were also analysed in terms of structural enthalpic group contributions.

Abstract The standard (p(o) = 0.1 MPa) molar enthalpies of formation in the condensed phase, Delta H-f(m)0, of 2,4-dichloro-5-methylpyrimidine, 2,4-dichloro-6-methylpyrimidine, 4,6-dichloro-2-methylpyrimidine and 4,6-dichloro-5-methylpyrimidine were derived from the standard molar energies of combustion, Delta U-c(m)0, in oxygen, to yield CO2 (g), N-2 (g) and HCl center dot 600H(2)O (l), at T = 298.15 K, measured by rotating bomb combustion calorimetry. The standard molar enthalpies of vaporization or sublimation, Delta H-g(cr, l)m(0), for these compounds, at T = 298.15 K were determined by high temperature Calvet microcalorimetry. Combining these values, the following enthalpies of formation in the gas phase, at T = 298.15 K, were then derived: 2,4-dichloro-5-methylpyrimidine, (79.6 +/- 4.1) kJ mol(-1), 2,4-dichloro-6-methylpyrimidine, (70.5 +/- 3.0) kJ mol(-1), 4,6-dichloro-2-methylpyrimidine, (68.7 +/- 3.3) kJ mol(-1), and 4,6-dichloro-5-methylpyrimidine, (78.1 +/- 2.5) kJ mol(-1). The gas-phase enthalpies of formation were also estimated by G3 theoretical calculations, which were extended to the computation of gas-phase enthalpies of formation of the other dichloromethylpyrimidine isomers, namely, 2,5-dichloro-4-methylpyrimidine, 4,5-dichloro-2-methylpyrimidine and 4,5-dichloro-6-methylpyrimidine, whose experimental study was not performed.