Publications

Abstract A combined experimental and computational study was developed to evaluate and understand the energetics and reactivity of formyl and methoxy a-naphthalene derivatives. Static bomb combustion calorimetry and the Calvet microcalorimetry were the experimental techniques used to determine the standard (p degrees = 0.1 MPa) molar enthalpies of formation, in the liquid phase, Delta H-f(m)o (1), and of vaporization, 4fH, at T= 298.15 K, respectively, of the two liquid naphthalene derivatives. Those experimental values were used to derive the values of the experimental standard molar enthalpies of formation, in the gaseous phase, Delta H-f(m)o(g), of 1-methoxynaphthalene, (-3.0 +/- 3.1) kJ mol(-1), and of 1-formylnaphthalene, (36.3 +/- 4.1) kJ mol(-1). High-level quantum chemical calculations at the composite G3(MP2)//B3LYP level were performed to estimate the values of the AfH(g) of the two compounds studied resulting in values in very good agreement with experimental ones. Natural bond orbital (NBO) calculations were also performed to determine more about the structure and reactivity of this class of compounds.

Abstract The standard (pA degrees A = 0.1 MPa) molar enthalpy of formation at T = 298.15 K for 4,5-dicyanoimidazole, in the crystalline phase, was derived from the standard molar energy of combustion measured by static bomb combustion calorimetry. This value and the literature value of the standard molar enthalpy of sublimation of the compound allow the calculation of the corresponding gas-phase standard molar enthalpy of formation, at T = 298.15 K. Additionally, theoretical calculations for 4,5-dicyanoimidazole were performed by density functional theory with the hybrid functional B3LYP and the 6-31G(d) basis set, extending the study to the 2,4- and 2,5-dicyanoimidazole isomers. Single-point energy calculations for both molecules were determined at the B3LYP/6-311+G(2df,2p) level of theory. With the objective of assessing the quality of the results, standard ab initio molecular orbital calculations at the G3 level were also performed. Enthalpies of formation, obtained using appropriate working reactions, were calculated and compared with the experimental data.

Abstract This work reports an experimental and computational thermochemical study of two aminothiazole derivatives, namely 2-aminothiazole and 2-aminobenzothiazole. The standard (p degrees =0.1 MPa) molar energies of combustion of these compounds were measured by rotating bomb combustion calorimetry. The standard molar enthalpies of sublimation, at T = 298.15 K, were derived from the temperature dependence of the vapor pressures of these compounds, measured by the Knudsen-effusion technique and from high temperature Calvet microcalorimetry. The conjugation of these experimental results enabled the calculation of the standard molar enthalpies of formation in the gaseous state, at T = 298.15 K, for the compounds studied. The corresponding standard Gibbs free energies of formation in crystalline and gaseous phases were also derived, allowing the analysis of their stability, in these phases. We have also estimated the gas-phase enthalpies of formation from high-level molecular orbital calculations at the G3(MP2)//B3LYP level of theory, the estimates revealing very good agreement with the experimental ones. The importance of some stabilizing electronic interactions occurring in the title molecules has been studied and quantitatively evaluated through Natural Bonding Orbital (NBO) of the corresponding wave-functions and their Nucleus Independent Chemical Shifts (NICS) parameters have been calculated in order to rationalize the effect of electronic delocalization upon stability.

Abstract Condensed phase standard (p degrees = 0.1 MPa) molar enthalpies of formation for 2-coumaranone and 3-coumaranone were derived from the standard molar enthalpies of combustion, in oxygen, at T = 298.15 K, measured by mini-bomb combustion calorimetry. Standard molar enthalpies of sublimation of both isomers were determined by Calvet microcalorimetry. These results were combined to derive the standard molar enthalpies of formation of the compounds, in gas phase, at T = 298.15 K. Additionally, accurate quantum chemical calculations have been performed using DFT methods and high level composite ab initio calculations. Theoretical estimates of the enthalpies of formation of the compounds are in good agreement with the experimental values thus supporting the predictions of the same parameters for isobenzofuranone, an isomer which has not been experimentally studied. The relative stability of these isomers has been evaluated by experimental and computational results. The importance of some stabilizing electronic intramolecular interactions has been studied and quantitatively evaluated through Natural Bonding Orbital (NBO) analysis of the wave functions and the nucleus independent chemical shift (NICS) of the studied systems have been calculated in order to study and establish the effect of electronic delocalization upon the relative stability of the isomers.

Abstract The present study reports the production and characterization of PEG-coated silica nanoparticles (SiNP-PEG) containing insulin for oral administration. High (PEG 20,000) and low (PEG 6000) PEG molecular weights were used in the preparations. SiNP were produced by sol gel technology followed by PEG adsorption and characterized for in vitro release by Franz diffusion cells. In vitro permeation profile was assessed using everted rat intestine. HPLC method has been validated for the determination of insulin released and permeated. Insulin secondary structure was performed by circular dichroism (CD). Uncoated SiNP allowed slower insulin release in comparison to SiNP PEG. The coating with high molecular weight PEG did not significantly (p>0.05) alter insulin release. The slow insulin release is attributed to the affinity of insulin for silanol groups at silica surface. Drug release followed second order kinetics for uncoated and SiNP PEG at pH 2.0. On the other hand, at pH 6.8, the best fitting was first-order for SiNP PEG, except for SiNP which showed a Boltzmann behavior. Comparing the values of half-live, SiNP PEG 20,000 showed a faster diffusion followed by Si-PEG 6000 and SiNP. CD studies showed no conformational changes occurring after protein release from the nanoparticles under gastrointestinal simulated conditions.

Abstract This study aims to investigate the effects of O-3 in protein content and immunoglobulin E (IgE)-binding profiles of Acer negundo, Platanus x acerifolia and Quercus robur pollen. Pollen was exposed to O-3 in an environmental chamber, at half, equal and four times the limit value for the human health protection in Europe. Pollen total soluble protein was determined with Coomassie Protein Assay Reagent, and the antigenic and allergenic properties were investigated by SDS-PAGE and immunological techniques using patients' sera. O-3 exposure affected total soluble protein content and some protein species within the SDS-PAGE protein profiles. Most of the sera revealed increased IgE reactivity to proteins of A. negundo and Q. robur pollen exposed to the pollutant compared with the non-exposed one, while the opposite was observed in P. x acerifolia pollen. So, the modifications seem to be species dependent, but do not necessarily imply that increase allergenicity would occur in atopic individuals.

Abstract The outcome of the Suzuki-Miyaura cross-coupling for the direct competition reaction between two boronic acids was evaluated under routine synthesis conditions. The reaction selectivity was found to depend on the amount of the base used, with fewer bases favoring the reactivity of the boronic acid with lower pK(a) (stronger acid). The dependence of the reaction selectivity on base stoichiometry was found to increase with the increase in the difference in the pK(a) values of the competing boronic acids. These results confirm a relationship between acid-base chemistry and the Suzuki-Miyaura reaction catalytic cycle. Moreover, the results indicate that under these specific conditions, the most reactive organoboron species toward transmetalation is the borate anion RB(OH)(3)(-) instead of the neutral boronic acid RB(OH)(2). Hence, the main role of the base in the reaction mechanism is to increase the reactivity of the boronic acid toward the Pd-halide complex by converting it into the respective organoborate. In addition, boric acid, an important reaction byproduct, affects the selectivity in the Suzuki reaction because its gradual formation in the reaction medium disturbs the acid-base equilibrium.

Abstract Freeze-drying has widely been applied to improve the stabilization of colloidal drug carriers. In the present study, the effect of cryoprotectants on the physicochemical characteristics of silica nanoparticles (SiNP) during the freeze-drying process has been extensively investigated. SiNP were synthesized by sol–gel technology and freeze-dried in the presence of sorbitol, trehalose, and/or mannitol at different concentrations and ratios. Dynamic light scattering (DLS), atomic force microscopy (AFM), X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC) have been used for particle characterization after freeze-drying. Based on the obtained results, SiNP in the presence of mannitol showed a more crystalline behavior in comparison to nanoparticles with sorbitol or trehalose (confirmed by DSC and XRD). SiNP in the presence of trehalose showed a more crystalline structure than SiNP in the presence of sorbitol. However, trehalose was more efficient in preserving the particle size of nanoparticles during the freeze-drying process. The optimal concentration of trehalose for preserving silica nanoparticles was 10 % at a ratio of (1:1). During the freeze-drying process, trehalose is able to replace water molecules due to the strong interaction via hydrogen bounds between silanol groups present in SiNP surface and the sugar, forming a stable layer around the particle and thus preserving the particle physical properties.

Abstract The self-association equilibrium constants, K-ass, for the dimerization of some small oligothiophenes in acetone, acetonitrile and chloroform were measured by H-1 NMR spectroscopy. The gas phase interaction energies for some oligothiophene dimers were determined by computational quantum chemistry. The H-1 NMR results indicate that K-ass generally increases with the chain length (the number of thienyl rings, n) and solvent polarity; however, K-ass for thiophene (n = 1) was found to be higher than for the bithiophenes (n = 2). The linear oligothiophenes 2,2'-bithiophene and 2,2',5',2 ''-terthiophene were found to self-associate less than their corresponding nonlinear isomers 3,30-bithiophene and 3,2',5',3 ''-terthiophene in solution and in the gas phase. For a-quaterthiophene (n = 4) K-ass in solution was found to be smaller than expected. The non-linear dependence of the standard molar Gibbs energy of self-association, Delta(ass)G(m)(0), on the chain length in solution could be nicely reproduced and related to the conformational entropy change of dimerization. It was observed that the melting properties of oligothiophenes correlate well with their tendency to self-associate, with more self-association leading to increased liquid stability, and thus lower melting temperatures. These results highlight the relevance of self-association in isotropic systems for the correct molecular interpretation of phase equilibria.

Abstract An experimental and theoretical study on the phase and molecular stability of Mq(3) (M = Al, Ga, and In; q = 8-hydroxyquinoline) is presented. The results suggest that the energy difference between the meridional and facial isomers of Mq(3) shall be significantly lower than previously though and provide an explanation for the reported mer-fac solid-solid transition. The first accurate vapor pressure measurements for Alq(3), Gaq(3), and Inq(3) are presented, which are of great relevance for the manufacturing of thin films by vacuum deposition. Phase transition thermodynamics indicates higher cohesive energies of the mer-isomers and an entropic differentiation that can be associated with the different molecular symmetry of the mer- and fac-isomers.