The role of the exchange-correlation density functional (PBE, PW91, RevPBE) and of surface relaxation in the determination of the adsorption energies, reaction energy barriers, and reaction rate constants has been analyzed taking water dissociation on Cu(111) surface as a test case. The PBE and PW91 functionals yield similar adsorption geometries and, adsorption and activation energies, but differ significantly from RevPBE results. For each of the functionals tested, surface relaxation was found to have only a minor effect on the calculated (co)adsorption geometries and (co)adsorption energies. The calculated energy barriers for water dissociation are more affected by the functional used, especially in the case of the RevPBE, with obvious implications on the calculated energy barriers and derived reaction rate constants. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3149851]

The role of the step sites in the water gas shift reaction catalyzed by Cu surfaces has been studied by using the Cu(321)-stepped surface as a representative model and periodic density functional theory within a supercell approach. Several reaction pathways were considered and the corresponding transition states for the elementary steps on each pathway were located and characterized. It was found that the presence of steps favors the associative route through the carboxyl intermediate assisted by co-adsorbed OH. The presence of step sites decreases the activation energy barriers for the rate-limiting steps, compared to the perfect Cu(111) surface. Reaction rate constants for the different pathways involved in the two molecular mechanisms, obtained from transition state theory, are reported. Finally comparison to previous work allows one to propose a useful Bronsted-Evans-Polanyi relationship.

We present results of detailed atomistic modeling of the early stages of the synthesis of periodic mesoporous silica using molecular dynamics. Our simulations lead to the proposal of a mechanism that validates several previous experimental and modeling studies and answers many controversial issues regarding the synthesis of mesoporous silicas. In particular, we show that anionic silicates interact very strongly with cationic surfactants and, significantly adsorb on the surface of micelles, displacing a fraction of previously bound bromide counterions. This induces an increase in micelle size and also enhances silica condensation at the micelle surface. The presence of larger silica aggregates in solution further promotes the growth of micelles and, by binding to surfactant molecules in different micelles, their aggregation. This work demonstrates the crucial role played by silica in influencing, by way of a cooperative templating mechanism, the structure of the eventual liquid-crystal phase, which in turn determines the structure of the porous material.

Molecular dynamics simulations of the wild-type and variant forms of the mouse ferrochelatase in complex with the product (haem) have been performed using the GROMOS96 force field, in the NpT ensemble. Ferrochelatase, the last enzyme in the catalytic pathway of the haem biosynthesis, catalyses the reaction of insertion of a ferrous ion into protoporphyrin IX by distorting the planar geometry of the latter reactant. The simulations presented aim at understanding the role of active-site residues in this catalytic process. Analysis of the simulation trajectories explains the consequences of the mutations introduced and sheds more light on the role of the His209 residue in porphyrin macrocycle distortion. The function of residues coordinating propionate groups of the haem molecule is discussed in terms of stability of the substrate and product complexes.

This work aims at describing the electronic features of cocaine and how they are modified by the different substituents present in its metabolites. The QTAIM analysis of B3LYP and MP2 electron densities obtained with the 6-311++G** 6d basis set for cocaine and its principal metabolites indicates: (i) its positive charge is shared among the amino hydrogen. those of the methylamino group, and all of the hydrogens attached to the bicycle structure, (ii) the zwitterionic structure of benzoylecgonine can be described as two partial Charges of 0.63 au, the negative one shared by the oxygens of the carboxylate group, whereas the positive charge is distributed among, all the hydrogens that bear the positive charge in cocaine; (iii) its hydrogen bond is strengthened in the derivatives without benzoyloxy group and is also slightly strengthened as the size of the alkyl ester group at position 2 increases.

Potassium (K+) channel openers are a diverse group of compounds which are used for the treatment of diseases like angina pectoris, hypertension, congestive heart failure, anti-hypoglycemic (insulinoma), bronchial asthma, etc. R/S-3,4-dihydro-2,2-dimethyl-6-halo-4-(substituted phenylaminocarbonylamino)-2H-1-benzopyrans are a new series of ATP-sensitive potassium (KATP-pβ) channel openers selective towards pancreatic β-cells. QSAR modelling was done on these series of compounds to find a more active and selective KATP-pβ channel opener selective towards β-cells of pancreatic tissues. Wang-Ford charges, partition coefficient, molar refractivity, principle moment of inertia at X, Y and Z axes are used as predictor variables and logarithm of percentage of residual insulin secretion is treated as response variable for the modelling. Multiple linear regressions with factor analysis were performed to develop QSAR models. Four equations were obtained using different combinations of the predictor variables based on factor loadings. Regression coefficients of all descriptors used are significant at more than 95% level. Results showed that Wang-Ford charges on atom numbers 11, 17, 18, 19 and 21 are important for the inhibition of residual insulin secretion. The presence of electron withdrawing group at m- and p-position of phenyl ring B is required for the inhibition. The energy minimized geometry of the most active compound supported our modelling.

Motivation. Meningoencephalitis, caused by the virulent fungus Cryptococcus neoformans, is an important cause of mortality in case of immunocompromised individuals, and new antifungal agents are required to treat such infections. Coumarins have antimeningoencephalitic activity, and here we report our attempt to find out the structural features required for more active congeners. Method. In vitro antifungal activity of coumarins, expressed as MIC50 values (μg/mL) was considered as the biological activity parameter. QSAR study of the data set of coumarins was performed using different parameters, namely physicochemical, topological, geometrical, constitutional, and semiemperical quantum chemical descriptors as well as whole molecular descriptors. Multiple regression analyses were performed to develop QSAR models. Results. The QSAR study highlights the atomic features and molecular descriptors, information content descriptors, topological and constitutional descriptors that affect the antifungal activity of these coumarin analogs. © 2009 BioChem Press.