Angiotensin II (AngII) is an octapeptide hormone, which plays a very important role in the blood pressure control mechanism. The excess production of this hormone is one of the main causes of hypertension illness. The antagonists for AngII Atl receptor constitute some of the most effective antihypertension drugs. In this work, both tested typel AngII antagonists as well as new modeled antagonists (obtained by substitution of nonspecific amino acids by noncode residues (Sarcosine (Sar) and several C-alpha,C-alpha-dialkylglycines)) were simulated in dimethyl sulfoxide (DMSO) using molecular dynamics (MD). A number of common structural characteristics were identified on the active (and potentially active) simulated analogs, which seem to be correlated with their antagonistic activity. Two of the designed analogs were proposed as possible antagonists.

Adsorption, of the methoxy radical on clean and on low oxygen precovered Ru(0001) metallic surfaces has been studied by densityfunctional theory cluster calculations. Methoxy is predicted to be preferentially chemisorbed on both hollow sites (hep and fcc) of such surfaces, and adopts an upright orientation (C-3, local symmetry). Such prediction is supported by the good agreement found between the calculated vibrational frequencies and the experimentally observed RAIRS spectra. Regarding the charge transfer process between the adsorbate and the surface, our results suggest that the bonding is dominantly polar covalent which arises from a charge donation from the ruthenium surface to the radical, and the co-adsorbed electronegative oxygens deplete slightly the surface electron density. However, the major difference is not induced through much O-Ru bonding, but indirectly, by lowering the valence d-band center of the system. This results in a lower adsorption energy for methoxy than on the clean Ru(0001) surface, in accordance with experimental data. Further, accordingly to the present calculations, the radical is expected to dissociate or desorb more easily on the modified surface but with no participation from the co-adsorbed oxygen atoms.

A series of ab initio and DFT calculations have been performed to study a natural compound often present in human diet, namely the amide of caffeic acid: 3-(3,4-dihydroxyphenyl)-2-propen-amide (ACA). Several molecular properties have been computed for this amide, such as potential energy profiles for internal rotation about different bonds, minimal conformer structures and corresponding vibrational frequencies. Twelve possible unlike conformations were found for ACA, adopting the amide group in all of them a non co-planar conformation. The conformational preferences of this amide are determined mainly by the degree of intra-molecular hydrogen bonding but non-bonding repulsions and conformational flexibility play also a key role. In all cases, the calculated properties are in good agreement with both experimental and theoretical data obtained for related molecular systems.

Spin-polarized density functional theory based calculations within the GGA/PW91 exchange-correlation functional have been carried out to investigate the interaction of atomic and molecular oxygen on the Au(321) surface modeled by a periodic supercell approach. It was found that the atoms prefer interaction with surface cavities, while in the case of molecules, adsorption is more favorable if the molecular axis is parallel to the surface terraces on bridge or nearby bridge sites. Further, the interaction of separated atoms with the Au(321) surface may well induce, at a relatively low energetic cost, strong surface relaxation. The dissociation of molecular oxygen on the Au(321) surface is exothermic, and the barrier for the dissociation reaction, determined using the climbing-image nudged elastic band method, is 1.00 eV and with an interatomic oxygen distance for the transition states of similar to 1.91 angstrom.

The interaction between glucose oxidase (GOx) and phospholipid monolayers is studied at the 1, 2-dichloroethane/water interface by electrochemical impedance spectroscopy. Electrochemical experiments show that the presence of GOx induces changes in the capacitance curves at both negative and positive potentials, which are successfully explained by a theoretical model based on the solution of the Poisson-Boltzmann equation. These changes ore ascribed to a reduced partition coefficient of GOx and on increase of the permittivity of the lipid hydrocarbon domain. Our results show that the presence of lipid molecules enhances the adsorption of GOx molecules at the liquid/liquid interface. At low lipid concentrations, the adsorption of GOx is probably the first step preceding its penetration into the lipid monolayer. The experimental results indicate that GOx penetrates better and forms more stable monolayers for lipids with longer hydrophobic toils. At high GOx concentrations, the formation of multilayers is observed. The phenomenon described here is strongly dependent on 1) the GOx and lipid concentrations, 2) the nature of the lipid, and 3) the potential drop across the interface.

We predict the soil sorption coefficients of 163 non-ionic organic pesticides performing a QSPR treatment. A pool containing 1247 theoretical descriptors is explored simultaneously encoding different aspects of the topological, geometrical, and electronic molecular structure. The application of Forward Stepwise Regression, Genetic Algorithms and the Replacement Method leads to an optimal six-parameter equation characterized with R = 0.949 and that also exhibits good cross-validated predictive ability, R(1-25%-O) = 0.916. This model compares fairly well with a previously reported QSPR on the same data set with R=0.904.

Malaria is nowadays a worldwide and serious problem with a significant social, economic, and human cost, mainly in developing countries. In addition, the emergence and spread of resistance to existing antimalarial therapies deteriorate the global malaria situation, and lead thus to an urgent need toward the design and discovery of new antimalarial drugs. In this work, a QSAR predictive model based on GETAWAY descriptors was developed which is able to explain with, only three variables, more than 77% of the variance in antimalarial potency and displays a good internal predictive ability (of 73.3% and 72.9% from leave-one-out cross-validation and bootstrapping analyses, respectively). The performance of the proposed model was judged against other five methodologies providing evidence of the superiority of GETAWAY descriptors in predicting the antimalarial potency of the bisbenzamidine family. Moreover, a desirability analysis based on the final QSAR model showed that to be a useful way of selecting the predictive variable level necessary to obtain potent bisbenzamidines. From the proposed model it is also possible to infer that elevated high atomic masses/polarizabilities/van der Waals volumes could play a negative/positive/positive role in the molecular interactions responsible for the desired drug conformation, which is required for the optimal binding to the macromolecular target. The results obtained point out that our final QSAR model is statistically significant and robust as well as possessing a high predictive effectiveness. Thus, the model provides a feasible and practical tool for looking for new and potent antimalarial bisbenzamidines.

For the first time, the partition coefficients of the ionized forms of several opioids, amphetamine-like drugs, and their metabolites were determined by studying their ionic transfer process across the bare interface water/organic solvent. The ionic partition coefficients of the monocationic forms of 12 compounds heroin, 6-monoacetylmorphine (6-MAM), morphine, acetylcodeine, codeine, dihydrocodeine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"), 3,4-methylenedioxyamphetamine (MDA), 3-methoxy-alpha-methyldopamine (3-OMe-alpha-MeDA), and alpha-methyldopamine (alpha-MeDA)-were attained using electrochemical measurements, by cyclic voltammetry, at the interface between two immiscible electrolyte solutions (ITIES). Then the acquired lipophilicity values were correlated to the chemical structure of the compounds and with the metabolic pathways central to each class of drugs. Although the mechanisms of biotoxicity of this type of drugs are still unclear, the data obtained evidence that the lipophilicity of metabolites may be a contributing factor for the qualitative differences found in their activity. In addition, the partition coefficients of the ionic drugs were calculated using three available software packages: ModesLab, Dragon, and HyperChem. As shown by cross-comparison of the experimental and calculated values, HyperChem was the most reliable software for achieving the main goal. The data obtained so far seem to be correlated to the proposed metabolic pathways of the drugs and could be of great value in understanding their pharmacological and/or toxicological profiles at the molecular level. This study may also contribute to gaining an insight into the mechanisms of biotransportation of this type of compounds given that the ionic partition coefficients reflect their ability to cross the membrane barriers.