Publications

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.

Abstract The fluorescence spectroscopy technique is an accurate method and has great utility in the interpretation of complex systems based on several emission bands. An interpretation of the system requires determination of the number, positions and intensities of the spectral components. In this work, the emission spectra of the synthesized ZnSe complex coated with O-phosphorylethanolamine (ZnSe-PEA), both with and without thiol DAB dendrimer generation 5 (S-DAB G(5)), were analyzed using a combination of asymmetric (log-normal) and symmetric (Gaussian) models. The method applied for the deconvolution of fluorescence spectra has proven to be very sensitive for observing the stability of the ZnSe-PEA complex after binding with S-DAB. The ZnSe-PEA emission spectrum contains two components. The positions of the emission maxima of these two components are not significantly affected by the presence of S-DAB G(5) in the complex, which revealed the presence of a stable complex at a pH of 7. By applying the spectral deconvolution method, strong evidence was obtained that suggested that the ZnSe-PEA complex is stable after complexation with S-DAB G5.

Abstract Thermochemical and thermodynamic properties of 2-, 3- and 4-iodonitrobenzene have been determined using a combination of calorimetric and effusion techniques as well as computational calculations. The standard (p degrees = 0.1 MPa) molar enthalpies of formation, in the crystalline state, Delta H-f(m degrees)(cr), at T = 298.15 K, were derived from the standard molar enthalpies of combustion, Delta H-c(m)degrees(cr), in oxygen, to yield CO2(g), N-2(g), and I-2(cr), at T = 298.15 K, measured by rotating bomb combustion calorimetry. The standard molar enthalpies of sublimation of these compounds, Delta(g)(cr) H-m(degrees), at T = 298.15 K, were determined using high temperature Calvet microcalorimetry. The Knudsen mass-loss effusion technique was used to determine the standard molar enthalpies, entropies and Gibbs free energies of sublimation, at T = 298.15 K, of the three studied compounds. The combination of some of the referred thermodynamic parameters yielded the standard (p degrees = 0.1 MPa) molar enthalpies of formation in the gaseous phase, at T = 298.15 K, of the three isomers: Delta H-f(m)degrees(2 - iodonitrobenzene, g) = (178.8 +/- 1.5) kJ . mol(-1), Delta H-f(m)degrees(3 - iodonitrobenzene, g) = (155.4 +/- 1.8) kJ . mol(-1) and Delta H-f(m)degrees(4 - iodonitrobenzene, g) = (151.8 +/- 1.6) kJ . mol(-1). The results were analyzed and interpreted in terms of enthalpic increments and molecular structure. Using the empirical scheme developed by Cox, the values of the standard molar enthalpies of formation in the gaseous phase were estimated and afterwards compared with the ones obtained experimentally, being both interpreted in terms of the molecular structure of the compounds. For comparison purposes, standard molecular calculations at the B3LYP6-311++ G(d, p) level were performed, and the gas-phase enthalpies of formation of the three compounds were estimated; the results are in good agreement with experimental data. Furthermore, the molecular structures of the three molecules were established and the structural parameters were determined at the B3LYP/6-311++ G(d, p) level of theory. The computational study was also extended to the determination of proton and electron affinities, basicities, and adiabatic ionization enthalpies.