Publications

Abstract In the face of a growing human population and increased urbanization, the demand for pesticides will simply rise. Farmers must escalate yields on increasingly fewer farm acres. However, the risks of pesticides, whether real or perceived, may force changes in the way these chemicals are used. Scientists are working toward pest control plans that are environmentally sound, effective, and profitable. In this context the development of new pesticide formulations which may improve application effectiveness, safety, handling, and storage can be pointed out as a solution. As a contribution to the area, the microencapsulation of the herbicide oxadiargyl (OXA) in (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CD) was performed. The study was conducted in different aqueous media (ultrapure water and in different pH buffer solutions). In all cases an increment of the oxadiargyl solubility as a function of the HP-beta-CD concentration that has been related to the formation of an inclusion complex was verified. UV-Vis and NMR experiments allowed concluding that the stoichiometry of the OXA/HP-beta-CD complex formed is 1:1. The gathered results can be regarded as an important step for its removal from industrial effluents and/or to increase the stabilizing action, encapsulation, and adsorption in water treatment plants.

Abstract The present article involves a comparative study of the influence of oxygen or sulfur heteroatoms present in the central ring of polycyclic compounds, in order to clarify the correlation between the respective thermophysical or thermochemical properties and structural characteristics. Considering the importance of these types of compounds for their broad spectrum of application in diverse fields, from pharmacology to the development of new materials, the critical interpretation of such properties for their crucial role in the reactivity of these substances is of great interest. Knowledge on these thermodynamic data for key compounds is also relevant to the prediction and understanding of the properties and behavior of other parent compounds.

Abstract A comprehensive analysis of the thermochemical properties of levoglucosan, using static bomb combustion calorimetry, Knudsen effusion technique, and differential scanning calorimetry, is presented. The experimental results allow us to derive the enthalpy of formation, in the gaseous phase, and thereafter to do a comparison with the same parameter obtained computationally. The good agreement between the experimental,, and computational results gives confidence to our determinations, particularly when they are compared with others already reported in literature. After testing the computational methodology, the ionization energy, electron affinity, proton affinity, gas-phase basicity, gas-phase acidity, and bond dissociation enthalpies of levoglucosan were also obtained. The presence of intramolecular hydrogen bonds in the most stable conformation of levoglucosan was verified by applying Quantum Theory of Atoms in Molecules calculations. Furthermore, a joint differential scanning calorimetry and temperature dynamic Fourier transform infrared (FT-IR) spectroscopic study was used to study the crystalline phase of levoglucosan between 298.15 K and the melting

Abstract Adenosine receptors (ARs) are signaling molecules ubiquitously expressed in a wide variety of tissues in the human body. ARs mediate physiological functions by interacting with four subtypes of G-protein-coupled receptors, namely A(1), A(2A), A(2B) and A(3). The A(3) AR, probably the most studied subtype, is also ubiquitously expressed, with high levels in peripheral organs and low levels in the brain. This type of AR is involved in a variety of important pathophysiological processes, ranging from modulation of cerebral and cardiac ischemic damage to regulation of immunosuppression and inflammation. Consequently, the development of potent and selective A(3) AR ligands as promising therapeutic options for a variety of diseases has been a prime subject of medicinal chemistry research for more than two decades. Among the plethora of approaches applied quantitative structure activity relationships (QSAR) stands out for being largely employed due to their potential to increase the efficiency at initial stages of the drug discovery process. So, we provide a review of the main QSAR studies devoted to the design, discovery and development of agonist and antagonist A(3) adenosine receptor ligands. Common pitfalls of these QSAR applications and the current trends in this area are also analyzed.

Abstract Quantitative structure-activity relationship (QSAR) models have application in bioorganic chemistry mainly to the study of small sized molecules while applications to biopolymers remain not very developed. MicroRNAs (miRNAs), which are non-coding small RNAs, regulate a variety of biological processes and constitute good candidates to scale up the application of QSAR and complex network (CN). In this work, we selected microRNAs and predicted activity profile subsequently represented as a large network, which may be used to identify stem cell microRNAs with similar action. The propensity of a small RNA sequence to act as miRNA depends on its secondary structure, which one can explain in terms of folding thermodynamic and topological parameters; these can be used for fast identification of miRNAs at early stages of development of stem cells, and gain clarity inside cellular differentiation processes and diseases such as cancer. First, we calculated thermodynamic parameters and topological descriptors for 432 small RNA sequences. The model correctly recognized 203 of smiRNAs (94.0%) and 216 of non-smiRNAs (100.0%) divided into both training and validation series used to extend model validation for network construction. ROC curve analysis (area = 0.99) demonstrated that the present model significantly differentiates from a random classifier. In addition, a double ordinate cartesian plot of cross-validated residuals, standard residuals and leverages defined the domain of applicability of the model as a squared area within +/- 2 band for residuals and a leverage threshold of h = 0.0466. Last, we accounted for the methodology to combine QSAR and CN to carry out a study that would allow us to differentiate the activity of smiRNAs. The network predicted has 216 nodes (smiRNAs), 1948 edges (pairs of smiRNAs with similar activity), and low coverage density d = 8.4%. Comparative studies with real networks reveal that our network apparently has not only an ideal behavior but also resembles the known network models in different aspects. The combination of QSAR and CN is used for quickly accurate selection of new smiRNAs with potential use in bioorganic and medicinal chemistry.

Abstract Alzheimer's disease (AD) has become a health problem to societies worldwide affecting millions of people. AD normally ensues in middle and late life but its specific cause remains unknown. Besides amyloid-deposition and hyperphosphorylated tau protein, increased production of reactive species (RS) has also been described to be a hallmark in early steps of this disorder. Antioxidant therapy has received considerable attention over the last years as a promising approach to delay or slow the neurodegeneration progression in AD either by boosting the pool of endogenous antioxidants (e. g. vitamins, coenzyme Q(10) or melatonin) or by the intake of dietary antioxidants, such as phenolic compounds of flavonoid or non-flavonoid type. However, the majority of antioxidants studied so far have limited success in clinical trials, a fact that could be related to their poor distribution and with the inherent difficulties to cross the blood brain barrier and attain the target sites. Despite the evidence that different classes of antioxidants are neuroprotectants in vitro, the clinical data is not consistent. Alzheimer's disease and antioxidant therapy is still an open question: the research is far from the end but the success may not be so time-consuming if the data obtained so far are gathered and rationally analyzed either by checking new targets or by the obtention of new and effective compounds, for instance by the rational modification of the previous ones.

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.