Publications

Abstract The vapour pressures of the three crystalline isomers of aminobenzamide were measured using the Knudsen mass-loss effusion technique. From the temperature dependence of the vapour pressures, the standard (p degrees = 0.1 MPa) molar enthalpies, Gibbs energies and entropies of sublimation, at T = 298.15 K, were derived. The standard molar enthalpies of formation of the three isomeric aminobenzamides in the crystalline phase, at T = 298.15 K, were determined from static bomb calorimetric experiments. These values were combined with the results of standard molar enthalpies of sublimation to derive the standard molar enthalpy of formation in gaseous phase, at T = 298.15 K, of ortho-aminobenzamide, -(113.1 +/- 1.5) kJ.mol(-1), meta-aminobenzamide, -(98.9 +/- 1.6) kJ.mol(-1), and para-aminobenzamide, -(100.3 +/- 1.6) kJ.mol(-1). The temperature and molar enthalpy of fusion of the studied compounds were measured using differential scanning calorimetry. Additionally, very high-level quantum-chemical calculations at the composite G3 level have been conducted in an attempt to accurately describing the energetic of all isomers. The experimentally observed enthalpies of formation have been fully corroborated by the very accurate calculations.

Abstract The structural changes caused by the substitution of the aromatic moiety in (2S)-2-benzyl-3-dehydroquinic acids and its epimers in C2 by electron-withdrawing or electron-donating groups in type II dehydroquinase enzyme from M. tuberculosis and H. pylori has been investigated by structural and computational studies. Both compounds are reversible competitive inhibitors of this enzyme, which is essential in these pathogenic bacteria. The crystal structures of M. tuberculosis and H. pylori in complex with (2S)-2-(4-methoxy) benzyl- and (2S)-2-perfluorobenzyl-3-dehydroquinic acids have been solved at 2.0, 2.3, 2.0, and 1.9 Å, respectively. The crystal structure of M. tuberculosis in complex with (2R)-2-(benzothiophen-5-yl)methyl-3-dehydroquinic acid is also reported at 1.55 Å. These crystal structures reveal key differences in the conformation of the flexible loop of the two enzymes, a difference that depends on the presence of electron-withdrawing or electron-donating groups in the aromatic moiety of the inhibitors. This loop closes over the active site after substrate binding, and its flexibility is essential for the function of the enzyme. These differences have also been investigated by molecular dynamics simulations in an effort to understand the significant inhibition potency differences observed between some of these compounds and also to obtain more information about the possible movements of the loop. These computational studies have also allowed us to identify key structural factors of the H. pylori loop that could explain its reduced flexibility in comparison to the M. tuberculosis loop, specifically by the formation of a key salt bridge between the side chains of residues Asp18 and Arg20. © 2012 American Chemical Society.

Abstract Herein we report comparative binding energy (COMBINE) analyses to derive quantitative structure-activity relationship (QSAR) models that help rationalize the determinants of binding affinity for inhibitors of typeII dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway. Independent COMBINE models were derived for Helicobacter pylori and Mycobacterium tuberculosis DHQ2, which is an essential enzyme in both these pathogenic bacteria that has no counterpart in human cells. These studies quantify the importance of the hydrogen bonding interactions between the ligands and the water molecule involved in the DHQ2 reaction mechanism. They also highlight important differences in the ligand interactions with the interface pocket close to the active site that could provide guides for future inhibitor design. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Abstract For the first time, a volatility study of the 1-ethylpyridinium bis(trifluoromethylsulfonyl) imide ([C-2-Py][ NTf2], CAS: 712354-97-7), 1-propylpyridinium bis(trifluoromethylsulfonyl) imide ([C3Py][NTf2]) and 1-butylpyridinium bis(trifluoromethylsulfonyl) imide ([C4Py][NTf2], CAS: 187863-42-9) ionic liquids, is presented. The vapor pressures as a function of temperature, for this ionic liquids were measured and the thermodynamic properties of vaporization were derived. The analysis and rationalization of the obtained results for the alkylpyridinium based ionic liquids was done based on the comparison with the [C(N-1)C(1)im][NTf2] (N = 3-5). The volatility of pyridinium is five times lower than the imidazolium based ionic liquids and that is driven by their higher enthalpy of vaporization.

Abstract The self-aggregation behavior of the double-chained ionic liquid (IL) 1,3-didecyl-2-methylimidazolium chloride ([C(10)C(10)mim]Cl) in aqueous solution has been investigated with a number of different experimental techniques Two cmc values (cmc(1) and cmc(2)) are obtained from conductivity measurements. The fraction of neutralized charge on the micellar surface suggests that cmc(1) corresponds to the formation of spherical micelles and cmc(2) to the transition from spherical to cylindrical micelles. Data obtained from fluorescence spectroscopy (using pyrene and Nile red as chemical probes), fluorescence anisotropy (using rhodamine B as probe), and chemical shift H-1 NMR (in D2O) provide a picture that is also consistent with a sphere-to-cylinder transition. This structural change is further confirmed by diffusion-ordered NMR spectroscopy (DOSY), from the self-diffusion coefficients for surfactant unimer and aggregates. Furthermore, a third evolution from cylindrical micelles to bilayer aggregates is proposed from the analysis of diffusion coefficients at high surfactant concentration ([IL] > 0.2 M). Phase scanning experiments performed with polarized light microscopy clearly demonstrate the presence of a lamellar liquid crystalline phase at very high IL concentration, thus confirming the coexistence of bilayer structures with elongated micelles, found at lower concentration. Additionally, [C(10)C(10)mim]Cl micelles are proposed as novel reaction media, as evidenced by the solvolysis reaction of 4-methoxybenzenesulfonyl chloride (MBSC).

Abstract A brief review of the experimental methods used to evaluate vapour pressures and sublimation enthalpies is presented. The methods discussed have been used for determining the results of several substituted benzenes that were collected in a database, with the main purpose of developing new estimation methods of these thermodynamic properties. A critical evaluation of the two most used calorimetric techniques for determining enthalpies of sublimation is also addressed.

Abstract In this work is investigated why the entrance of a nitrogen atom in the ring of cis-2-hydroxypyridine and 2-pyridinone, resulting in cis-4-hydroxypyrimidine and 4(3H)-pyrimidinone, respectively, shifts the tautomeric equilibrium from the hydroxyl form, in the pyridine derivative, to the ketonic form, in the pyrimidine derivative. The conclusions obtained for these model systems allow us to understand how to control the gaseous-phase keto enol tautomeric equilibrium in nitrogen heterocyclic rings and justify the tautomeric preference in pyrimidine nucleobases. The experimental and computational energetics of tautomeric equilibrium were interpreted in terms of the aromaticity, intramolecular hydrogen bonds, and electronic delocalization, evaluated using nucleus independent chemical shifts, quantum theory of atoms in molecules, natural bond orbital analysis, and the thermodynamic changes of appropriate reactions.

Abstract Over the last decade ionic liquids appeared as potential entrainers for extractive distillation processes. However experimental vapor-liquid equilibrium data for ionic liquid containing systems is still scarce since most conventional equilibrium cells are not adequate for these systems. To overcome that limitation a new isobaric microebulliometer, operating at pressures ranging from 0.05 to 0.1 MPa and requiring a sample volume lower than 8 mL was developed and validated in this work. The new apparatus was used to determine isobaric VLE data at pressures of 0.05, 0.07 and 0.1 MPa for eight binary mixtures of 1-ethyl-3-methylimidazolium chloride ([C(2)mim][Cl]), 1-butyl-3-methylimidazolium chloride ([C(4)mim][Cl]), 1-hexyl-3-methylimidazolium chloride ([C(6)mim][Cl]), and choline chloride ([N-111(2OH)[Cl]) with water and ethanol. The experimental data here measured were correlated with the NRTL model.

Abstract The enthalpy of hydrogenation of uracil was derived from the experimental enthalpies of formation, in the gaseous phase, of uracil and 5,6-dihydrouracil, in order to analyze its aromaticity. The enthalpy of formation of 5,6-dihydrouracil was obtained from combustion calorimetry, Knudsen effusion technique and Calvet microcalorimetry results. High-level computational methods were tested for the enthalpy of hydrogenation of uracil, but only with G3 was possible to obtain results in agreement with the experimental ones. It was found that uracil possesses 30.0% of aromatic character in the gaseous phase. Using both implicit, explicit, and hybrid solvation methods, it was possible to obtain a reference value for the enthalpy of hydrogenation of uracil in the aqueous solution and the effect of polarity and hydrogen bonds on the aromaticity of uracil was analyzed. The value of the hydrogenation enthalpy of uracil in aqueous solution was compared with the experimental value in the crystal phase, also dominated by polarity and hydrogen bonds, derived from combustion calorimetry results. The supramolecular effects on the crystal lattice were explored by the computational simulation of pi-pi staking dimers and hydrogen bonded dimers.

Abstract Today, emerging and increasing resistance to antibiotics has become a threat to public health worldwide. Antimicrobial peptides own unique action mechanisms making peptide antibiotics an attractive therapeutic option against resistant bacteria. However, their high haemolytic activity lacks the selectivity required for a human antibiotic. Therefore, additional efforts are needed to develop new antimicrobial peptides that possess greater selectivity for bacterial cells over erythrocytes. In this article, we introduce a chemoinformatics approach to simultaneously deal with these two conflicting properties consisting on a multi-criteria virtual screening strategy based on the use of a desirability-based multi-criteria classifier combined with similarity and chemometrics concepts. Here we propose a new quantitative feature encoding information related to the desirability, the degree of credibility ascribed to this desirability and the similarity of a candidate to a highly desirable query, which can be used as ranking criterion in a virtual screening campaign, the Desirability-Credibility-Similarity (DCS) Score. The enrichment ability of a multi-criteria virtual screening strategy based on the use of the DCS Score it is also assessed and compared to other virtual screening options. The results obtained evidenced that the use of the DCS score seems to be an efficient virtual screening strategy rendering promising overall and initial enrichment performance. Specifically, by using the DCS score it was possible to rank a selective antibacterial peptidomimetic earlier than a biologically inactive or non selective antibacterial peptidomimetic with a probability of ca. 0.9.