Publications

Abstract A new electrically calibrated calorimetric system to measure heat capacities of solids has been designed and tested by determining the heat capacity of sapphire and benzoic acid in the temperature range 298-393 K. Comparison of the obtained results with recommended adiabatic calorimetry data showed that the maximum and average absolute deviations were 3.3% and 1.6%, respectively. The technique provides a convenient alternative to routine heat capacity determinations by DSC, since the experiments are faster and, in general, the results have better accuracy. In addition, the sample cells can be kept under argon or nitrogen atmosphere thus enabling the study of air sensitive compounds. © 2006 IOP Publishing Ltd.

Abstract The oxidative behaviour of fluoxetine was studied at a glassy carbon electrode in various buffer systems and at different pH using cyclic, differential pulse and square wave voltammetry. A new square wave voltammetric method suitable for the quality control of fluoxetine in commercial formulations has been developed using a borate pH 9 buffer solution as supporting electrolyte. Under optimized conditions, a linear response was obtained in the range 10 to 16 mu M with a detection limit of 1.0 mu M. Validation parameters such as sensitivity, precision and accuracy were evaluated. The proposed method was successfully applied to the determination of fluoxetine in pharmaceutical formulations. The results were statistically compared with those obtained by the reference high-performance liquid chromatographic method. No significant differences were found between the methods.

Abstract The standard (p(o) = 0.1 MPa) molar enthalpies of formation of the crystalline complexes of dibenzoylmethane (HDBM), thenoyltrifluoroacetone (HTTFA), monothiodibenzoylmethane (HDBMS), and monothiothenoyltrifluoroacetone (HTTFAS) of copper(II) were determined, at T = 298.15 K, by high precision solution-reaction calorimetry. The standard molar enthalpies of sublimation of the copper(II) beta-diketonate complexes were 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 copper(II)-ligand, (D-m)(Cu-L), were derived. [GRAPHICS]

Abstract A new Knudsen effusion apparatus, enabling the simultaneous operation of nine effusion cells at three different temperatures, is fully described. The performance of the new apparatus was checked by measuring the vapour pressures, between 0.1 Pa and 1 Pa, over ca. 20 K temperature intervals of benzoic acid, phenanthrene, anthracene, benzanthrone, and 1,3,5-triphenylbenzene. The derived standard molar enthalpies of sublimation are in excellent agreement with the mean of the literature values available for these five compounds and with the recommended values for four of them.

Abstract Nelfinavir (Viracept, Pfizer), and Amprenavir (Ageneraze(R), GlaxoSmithKline) are potent bioavailable inhibitors of the enzyme Protease (PR) of the Human Immunodeficiency Virus-1 (HIV-1), which have been developed by consistent structure-based drug design projects, and have been approved worldwide for the treatment of HIV infected patients. They act as competitive inhibitors, and tightly bind the active site of PR with high shape and electrostatic potential complementarily. However, the virus has shown the ability of fixating mutations which decrease the affinity of the antiretrovirals for the binding pocket of PR, although at the cost of decreasing (but to a minor extent) the affinity for the substrate. The consequent appearance of drug resistance compromised the long term efficacy of the drug. In this work we have extended such structure based drug design effort with computational methodologies, by performing very small substitutions in the inhibitors, directed at interacting with the most conserved amino acids. It is not possible to mutate the latter, at the cost of making the enzyme catalytically inactive. We show with a set of examples that significant increases in affinity can still be achieved without changing the overall structure, molecular mass and hydrophobicity of the inhibitors, thus preserving their very favourable ADME properties.

Abstract The standard (p degrees = 0.1 MPa) molar enthalpies of formation of crystalline 2,3,5-trimethylpyrazine-1,4-dioxide and 2,3,5,6-tetramethylpyrazine-1,4-dioxide were measured, at T = 298.15 K, by static bomb calorimetry and the standard molar enthalpies of sublimation, at T = 298.15 K, were obtained from Calvet microcalorimetric measurements. These values were used to derive the respective standard molar enthalpies of formation in gaseous phase. The mean N-O bond dissociation enthalpy has been calculated for both compounds. (c) 2006 Published by Elsevier B.V.

Abstract DFT calculations have been performed to investigate the effect of several different substituents on the N-O bond dissociation enthalpies of 2-substituted-quinoxaline-1,4-dioxides. Further, the influence of electron and proton affinities and also of N-O bond dissociation enthalpies on the antitumor activity of selected compounds is analyzed. In agreement with experimental data, the calculations suggest that Tirapazamine is more active than Quindoxin due to a much easier reduction and protonation of the former species accompanied by a weaker N-OH bond.

Abstract Computer simulations can be very useful in teaching chemical equilibrium like salt solubility. As a computer generated animation, Computer Simulations of Salt Solubility compares pair of compounds chosen like NaCL and CaCo3. The computer program simulates in a qualitative manner, the "before" and "after" states for the dissolution of equal amounts of NaCl and CaCO3 in identical amounts of water. Total entropy increases in the case of NaCl due to the increase of configurational disorder of salt ions. However, in the case of CaCO3, an identical effect is offset by the decrease of mobility of the water molecules associated with the dipositive calcium ion. Ion salvation is less relevant both in the case of the monocharged ions Na+ and Cl- and in the case of large ion CO3 2-. Same procedure can be done for MgCO3 and MgSO4 simulation.

Abstract Computer simulations of salt solubility used a Java applet and Web browser to present an animated illustration of differences in the solubility of salts. The simulation provides an animated, visual interpretation of the different solubilities of related salts based on simple entropy changes associated with dissolution: configurational disorder and thermal disorder. Pairs of compounds chosen for the animation are NaCl/CaCO3 and MgCO3/MgSO4. In the former case, both dissolution are almost athermic, hence the major differences are in configurational disorder and solvation effects. In the latter pair, the major difference lies in thermal disorder, as the dissolution of magnesium sulfate is quite exothermic. Changes in total entropy and in its components are represented qualitatively in bar graphs.