Publications

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.

Abstract Densities, viscosities and refractive index, as a function of temperature, and isobaric thermal expansion coefficient, were determined for 1-alkyl-3-methylimidazolium hexafluorophosphate, [C(N - 1)C(1)im]PF6] (where N = 5 to 10) series of ionic liquids. The density presents a regular decrease along the ionic liquid series, with no detectable alkyl chain length dependence of the thermal expansion coefficient. Both the refractive index and viscosity show a trend shift along the series around the [C(6)C(1)im][PF6] that could be associated to the impact of the change in the nanostructuration of the ionic liquids. The experimental results are compared with the analogous [C(N - 1)C(1)im][NTf2] series and the effect of the anion is analyzed. The sphericity of the [PF6](-) anion is reflected in the lower pre-exponential VTF parameter, A(eta), and the higher viscosity of the [C(N - 1)C(1)im][PF6]. when compared with the [C(N - 1)C(1)im][NTf2] series, is ruled by the higher energy barriers, which are related with stronger electrostatic interaction due to the low charge dispersion of the [PF6](-),anion.

Abstract The standard (p degrees = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at the reference temperature of 298.15 K, of 2-amino-4-methylpyrimidine ((98.1 +/- 1.6) kJ . mol(-1)), 2-amino-4,6-dimethylpyrimidine ((55.9 +/- 1.8) kJ . mol(-1)) and 4-amino-2,6-dimethylpyrimidine ((60.1 +/- 1.8) kJ . mol(-1)) were calculated from the enthalpies of formation, in the crystalline phase, and enthalpies of sublimation, derived, respectively, from static bomb combustion calorimetry and Knudsen effusion technique results. In order to quantify the resonance effects arising from the substitution on the pyrimidine ring, hypothetical isodesmic reactions were used to analyze the experimental gaseous-phase enthalpies of formation. The aromaticity of benzene, pyridine, pyrimidine and the substituted pyrimidines was investigated in terms of magnetic (NICS), geometric (HOMA), electronic (Shannon aromaticity, QTAIMs ring critical point properties and HOMO-LUMO gap), reactive (hardness), vibrational (Kekule mode) and spectroscopic (UV-Vis) properties.

Abstract Testing impulsive behavior in rodents is challenging and labor-intensive. We developed a new behavioral paradigm-the Variable Delay-to-Signal (VDS) test-that provides rapid and simultaneous assessment of response and decision impulsivity in rodents. Presentation of a light at variable delays signals the permission for action (nose poke) contingent with a reward. 2 blocks of 25 trials at 3 s delay flank a block of 70 trials in which light is presented with randomly selected 6 or 12 s delays. Exposure to such large delays boosts the rate of premature responses when the delay drops to 3 s in the final block, an effect that is blunted by an acute methamphetamine challenge and that correlates with the delay-discounting (DD) paradigm (choice impulsivity). Finally, as expected, treatment with the NMDA antagonist MK-801 caused a generalized response increase in all VDS blocks. The pharmacological validation, particularly with methamphetamine which has a well established dual effect on response and decision impulsivity, and the correlations between the impulsive behavior in the DD and VDS paradigms, suggests that the later is able to provide, in a single session, a multi-dimensional assessment of impulsive behavior.

Abstract Objectives With the aim of finding new adenosine receptor (AR) ligands based on the chalcone scaffold, we report the synthesis of a new series of coumarinchalcone hybrids and the pharmacological characterization of their actions at four subtypes of AR. Methods The synthesized compounds 510 were characterized in radioligand binding (A1, A2A and A3) and adenylyl cyclase activity assays (A2B) to determine the affinity of the compounds for the four human AR (hAR) subtypes. Key findings Coumarinchalcone hybrids were found to be ligands with a novel structure, not reported thus far, that showed varying affinity and selectivity for AR subtypes. Conclusions The coumarinchalcone hybrids in which ring B of the chalcone scaffold was a thiophene (compounds 5 and 9) were found to be the most potent compounds of the series. Compound 9, in which ring A of the chalcone moiety was the phenyl ring of the coumarin, showed similar activity against hA1, hA2A and hA3 ARs, while compound 5, in which ring A of the chalcone was substituted by the benzopyrone ring of the coumarin moiety, showed similar activity only at the hA3 AR and, therefore, was deemed to be selective (Ki (dissociation constant)=5160nm).